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Leeuwarden, Netherlands

Griepsma M.,University of Groningen | De Roy Van Zuidewijn D.B.W.,Medical Center Leeuwarden | Grond A.J.K.,Pathology Friesland | Siesling S.,Comprehensive Cancer Center the Netherlands | And 3 more authors.
Annals of Surgical Oncology | Year: 2014

Background. Residual breast tissue after a mastectomy can lead to a (second) primary breast cancer. The development of breast cancer after prophylactic mastectomy and the finding of normal breast tissue around a local recurrence support this assumption. The aim of the present study was to investigate the prevalence and localization of residual breast tissue after a mastectomy. Methods. A series of 206 women who underwent a mastectomy between January 2008 and August 2009 in 11 hospitals were enrolled onto this study after written informed consent was obtained. From each mastectomy specimen, a total of 36 samples were obtained from the superficial dissection plane at predetermined locations. The biopsy samples were analyzed for the presence of benign breast tissue in the inked superficial area. Differences in percentage of positive samples were analyzed by generalized estimating equations to account for their interdependence. Results. A total of 7,374 biopsy samples from 206 breast specimens of 206 patients were included in the analysis. In 76.2 % of the specimens (n = 157), one or more positive biopsy samples were found. The positive findings were found diffusely across the superficial dissection surface of the specimen with a significant predilection for the lower outer quadrant and the middle circle of the superficial dissection plane. Conclusions. After a mastectomy, there is a high probability of residual breast tissue. This tissue is predominantly located in the middle circle of the superficial dissection plane and in the lower outer quadrant. Surgeons should be aware of these locations so they may remove as much of the benign breast tissue as possible. © 2013 Society of Surgical Oncology.


Wieringa A.,University of Groningen | Boslooper K.,University of Groningen | Hoogendoorn M.,Medical Center Leeuwarden | Joosten P.,Medical Center Leeuwarden | And 10 more authors.
British Journal of Haematology | Year: 2014

An observational population-based cohort study was performed to investigate the role of comorbidity on outcome and treatment-related toxicity in patients with newly diagnosed advanced-stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Data for the clinical characteristics of 154 patients (median age 69 years), including Charlson Comorbidity Index (CCI), treatment, toxicity and outcome were evaluated. Forty-five percent of the patients had an International Prognistic index ≥3 and 16% had a CCI ≥2. The planned R-CHOP schedule was completed by 84% and 75% reached complete remission (CR). In those with CCI ≥2, 67% completed treatment with 46% CR. In patients with a CCI <2, overall survival (OS) after 1, 2 and 5 years was 84%, 79% and 65% respectively and it was 64%, 48% and 48% for those with CCI ≥2. Grade III/IV toxicity was documented in 53%, most frequently febrile neutropenia (27%) and infections (23%). In multivariate analysis CCI ≥2 and IPI ≥3 were independent risk indicators for OS and grade III/IV toxicity. In conclusion, comorbidity is an independent risk indicator for worse OS in patients with advanced DLBCL treated with R-CHOP by interference with intensive treatment schedules and more grade III/IV toxicity. Future studies are warranted to determine the optimal treatment approach in patients with significant comorbidities. © 2014 John Wiley & Sons Ltd.


Boslooper K.,Medical Center Leeuwarden | Kibbelaar R.,Pathology Friesland | Veeger N.J.G.M.,MCL Academy | Hovenga S.,Nij Smellinghe | And 7 more authors.
Leukemia and Lymphoma | Year: 2014

To assess treatment strategies, toxicity and outcome in very elderly patients (aged ≥ 75 years) diagnosed with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, an observational population-based cohort study was performed. From 103 patients with a median age of 81 years, data of clinical characteristics, treatment, toxicity and outcome were evaluated. Advanced stage DLBCL was documented in 74 patients. In 80 patients chemotherapy was initiated; 70 patients received rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). In this group, 39 patients completed all cycles and 30 patients achieved a complete remission. Severe chemotherapy-related toxicity occurred in 69%. Two-year overall survival was 70% for elderly patients who completed chemotherapy, 28% for those treated with incomplete or suboptimal chemotherapy and 21% for those receiving palliative radiotherapy or supportive care. In conclusion, the ability to complete R-CHOP was associated with better overall survival compared to other treatment strategies at the expense of severe treatment-related toxicity. © 2014 Informa UK, Ltd.


Van Der Logt E.M.J.,Pathology Friesland | Van Der Logt E.M.J.,University of Groningen | Kuperus D.A.J.,Pathology Friesland | Van Setten J.W.,Pathology Friesland | And 4 more authors.
PLoS ONE | Year: 2015

HER2 assessment is routinely used to select patients with invasive breast cancer that might benefit from HER2-targeted therapy. The aim of this study was to validate a fully automated in situ hybridization (ISH) procedure that combines the automated Leica HER2 fluorescent ISH system for Bond with supervised automated analysis with the Visia imaging D-Sight digital imaging platform. HER2 assessment was performed on 328 formalin-fixed/paraffinembedded invasive breast cancer tumors on tissue microarrays (TMA) and 100 (50 selected IHC 2+ and 50 random IHC scores) full-sized slides of resections/biopsies obtained for diagnostic purposes previously. For digital analysis slides were pre-screened at 20x and 100x magnification for all fluorescent signals and supervised-automated scoring was performed on at least two pictures (in total at least 20 nuclei were counted) with the D-Sight HER2 FISH analysis module by two observers independently. Results were compared to data obtained previously with the manual Abbott FISH test. The overall agreement with Abbott FISH data among TMA samples and 50 selected IHC 2+ cases was 98.8%(κ = 0.94) and 93.8% (κ = 0.88), respectively. The results of 50 additionally tested unselected IHC cases were concordant with previously obtained IHC and/or FISH data. The combination of the Leica FISH system with the D-Sight digital imaging platform is a feasible method for HER2 assessment in routine clinical practice for patients with invasive breast cancer. © 2015 van der Logt et al.


Moelans C.B.,University Utrecht | Kibbelaar R.E.,Pathology Friesland | Van Den Heuvel M.C.,Pathology Friesland | Castigliego D.,University Utrecht | And 2 more authors.
Cellular Oncology | Year: 2010

Background: Testing for HER2 amplification and/or overexpression is currently routine practice to guide Herceptin therapy in invasive breast cancer. At present, HER2 status is most commonly assessed by immunohistochemistry (IHC). Standardization of HER2 IHC assays is of utmost clinical and economical importance. At present, HER2 IHC is most commonly performed with the HercepTest which contains a polyclonal antibody and applies a manual staining procedure. Analytical variability in HER2 IHC testing could be diminished by a fully automatic staining system with a monoclonal antibody. Materials and methods: 219 invasive breast cancers were fully automatically stained with the monoclonal antibody-based Oracle HER2 Bond IHC kit and manually with the HercepTest. All cases were tested for amplification with chromogenic in situ hybridization (CISH). Results: HercepTest yielded an overall sharper membrane staining, with less cytoplasmic and stromal background than Oracle in 17% of cases. Overall concordance between both IHC techniques was 89% (195/219) with a kappa value of 0.776 (95% CI 0.698-0.854), indicating a substantial agreement. Most (22/24) discrepancies between HercepTest and Oracle showed a weaker staining for Oracle. Thirteen of the 24 discrepant cases were high-level HER2 amplified by CISH, and in 12 of these HercepTest IHC better reflected gene amplification status. All the 13 HER2 amplified discrepant cases were at least 2+ by HercepTest, while 10/13 of these were at least 2+ for Oracle. Considering CISH as gold standard, sensitivity of HercepTest and Oracle was 91% and 83%, and specificity was 94% and 98%, respectively. Positive and negative predictive values for HercepTest and Oracle were 90% and 95% for HercepTest and 96% and 91% for Oracle, respectively. Conclusion: Fully-automated HER2 staining with the monoclonal antibody in the Oracle kit shows a high level of agreement with manual staining by the polyclonal antibody in the HercepTest. Although Oracle shows in general some more cytoplasmic staining and may be slightly less sensitive in picking up HER2 amplified cases, it shows a higher specificity and may be considered as an alternative method to evaluate the HER2 expression in breast cancer with potentially less analytical variability. © 2010 - IOS Press and the authors. All rights reserved.

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