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Nijmegen, Netherlands

De Boer M.,Maastricht University | De Boer M.,Comprehensive Cancer Center East | Van Dijck J.A.A.M.,Comprehensive Cancer Center East | Bult P.,Radboud University Nijmegen | And 2 more authors.
Journal of the National Cancer Institute | Year: 2010

Background The prognostic relevance of isolated tumor cells and micrometastases in lymph nodes from patients with breast cancer has become a major issue since the introduction of the sentinel lymph node procedure. We conducted a systematic review of this issue.Methods Studies published from January 1, 1977, until August 11, 2008, were identified by use of MEDLINE, EMBASE, and the Cochrane Library. A total of 58 studies (total number of patients = 297533) were included and divided into three categories according to the method for pathological assessment of the lymph nodes: cohort studies with single-section pathological examination of axillary lymph nodes (n = 285638 patients), occult metastases studies with retrospective examination of negative lymph nodes by step sectioning and/or immunohistochemistry (n = 7740 patients), and sentinel lymph node biopsy studies with intensified work-up of the sentinel but not of the nonsentinel lymph nodes (n = 4155 patients). We used random-effects meta-analyses to calculate pooled estimates of the relative risks (RRs) of 5-and 10-year disease recurrence and death and the multivariably corrected pooled hazard ratio (HR) of overall survival of the cohort studies.Results In the cohort studies, the presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes was associated with poorer overall survival (pooled HR of death = 1.44, 95% confidence interval [CI] = 1.29 to 1.62). In the occult metastases studies, the presence (vs the absence) of occult metastases was associated with poorer 5-year disease-free survival (pooled RR = 1.55, 95% CI = 1.32 to 1.82) and overall survival (pooled RR = 1.45, 95% CI = 1.11 to 1.88), although these endpoints were not consistently assessed in multivariable analyses. Sentinel lymph node biopsy studies were limited by small patient groups and short follow-up.ConclusionThe presence (vs the absence) of metastases of 2 mm or less in diameter in axillary lymph nodes detected on single-section examination was associated with poorer disease-free and overall survival.

Schaapveld M.,Comprehensive Cancer Center North East | Jorna F.H.,University of Groningen | Aben K.K.H.,Comprehensive Cancer Center East | Aben K.K.H.,Radboud University Nijmegen | And 3 more authors.
American Journal of Surgery | Year: 2011

Background: Parathyroid carcinoma is a rare malignancy and generally is diagnosed after surgery for primary hyperparathyroidism. Lack of a preoperative diagnosis and ill-considered surgical planning with its impact on survival are ill-described. Methods: In a retrospective population-based cohort study the clinical features, treatment, recurrences, and survival of 41 parathyroid cancer patients are reported and compared with characteristics of patients with primary hyperparathyroidism. Results: Patients with parathyroid carcinoma had significantly higher serum parathyroid hormone and calcium levels compared with patients with primary hyperparathyroidism. Nineteen patients (46%) had a palpable neck mass. A parathyroid hormone level more than 3 times the upper normal limits was suspicious and levels more than 10 times carried a positive predictive value of 84% for carcinoma. Ten-year recurrence-free and disease-specific survival rates were 71% and 79%, respectively. Conclusions: Parathyroid hormone levels of more than 3 times upper normal limits, palpable neck mass, and profound hypercalcemia are suspicious signs of carcinoma necessitating surgical exploration by an experienced surgeon. © 2011 Elsevier Inc.

Grotenhuis A.J.,Radboud University Nijmegen | Vermeulen S.H.,Radboud University Nijmegen | Kiemeney L.A.,Radboud University Nijmegen | Kiemeney L.A.,Comprehensive Cancer Center East
Future Oncology | Year: 2010

After decades of research using a candidate gene approach, only NAT2 and GSTM1 have consistently been demonstrated to be germline genetic susceptibility markers for urinary bladder cancer (UBC). The recent shift to an agnostic genome-wide association approach led to the identification of several UBC susceptibility loci, and provided valuable leads for new mechanistic insights into UBC carcinogenesis. The markers do not have sufficient discriminatory ability yet to be applied for risk assessment in the population and the question is whether they ever will. Prognostic and predictive studies in UBC are still in their infancy compared with etiologic studies. In the future, focus on a genome-wide association approach possibly using whole-genome sequence data, consortia formation and meta-analyses, and blood and tumor tissue collection, preferably in the context of randomized controlled trials will stimulate well designed and sufficiently powered studies, and thereby enhance the elucidation of genetic prognostic and predictive markers. © 2010 Future Medicine Ltd.

Van Laarhoven H.W.M.,Radboud University Nijmegen | Schilderman J.,Radboud University Nijmegen | Verhagen C.A.H.H.V.M.,Radboud University Nijmegen | Verhagen C.A.H.H.V.M.,Comprehensive Cancer Center East | And 2 more authors.
Journal of Pain and Symptom Management | Year: 2011

Context: It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. Objectives: To assess the relationship of attitudes and emotions towards death and an afterlife with quality of life, depression and hopelessness in cancer patients without evidence of disease and advanced cancer patients facing death. Methods: Ninety-one cancer patients without evidence of disease and 57 advanced cancer patients completed the Dutch Attitudes Toward Death and Afterlife Scale. Emotions toward death were measured using the Self-Confrontation Method. Quality of life was measured with the Satisfaction with Life Scale and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire. Depression and hopelessness were measured with the Beck Depression Inventory for Primary Care and the Beck Hopelessness Scale. Results: Average scores on attitudes and emotions toward death and an afterlife were not significantly different between the two groups. However, in the no evidence of disease group, a negative association between negative emotions and social functioning was observed, which was not present in the advanced cancer group. In the advanced cancer group, associations were observed that were not present in the no evidence of disease group: positive associations between an explicitly religious attitude and global health status and between reincarnation belief and role and cognitive functioning, and a negative association between other-directed emotions and social functioning. Conclusion: Patients without evidence of disease and advanced cancer patients do not differ in attitudes or emotions toward death, but the relationship between these attitudes and emotions and aspects of quality of life varies. When there is no evidence of disease, negative emotions play the most important role, whereas in the advanced cancer situation, attitudes toward death and an afterlife, which may provide meaning and value, become more prominent. © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Van Der Post R.S.,Radboud University Nijmegen | Kiemeney L.A.,Radboud University Nijmegen | Kiemeney L.A.,Comprehensive Cancer Center East | Ligtenberg M.J.L.,Radboud University Nijmegen | And 7 more authors.
Journal of Medical Genetics | Year: 2010

Background: Colorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer. Methods: Carriers and first degree relatives of 95 families with a germline mutation in the MLH1 (n=26), MSH2 (n=43), or MSH6 (n=26) gene were systematically questioned about the occurrence of carcinoma. The cumulative risk of cancer occurring before the age of 70 years (CR70) was compared to the CR70 of the general Dutch population. Microsatellite instability (MSI) testing and/or immunohistochemistry (IHC) for mismatch repair proteins was performed on bladder tumour tissue. Results: Bladder cancer was diagnosed in 21 patients (90% men) from 19 Lynch syndrome families (2 MLH1, 15 MSH2, and 4 MSH6). CR70 for bladder cancer was 7.5% (95% CI 3.1% to 11.9%) for men and 1.0% (95% CI 0% to 2.4%) for women, resulting in relative risks for mutation carriers and first degree relatives of 4.2 (95% CI 2.2 to 7.2) for men and 2.2 (95% CI 0.3 to 8.0) for women. Men carrying an MSH2 mutation and their first degree relatives were at highest risks: CR70 for bladder and upper urinary tract cancer being 12.3% (95% CI 4.3% to 20.3%) and 5.9% (95% CI 0.7% to 11.1%). Bladder cancer tissue was MSI positive in 6/7 tumours and loss of IHC staining was found in 14/17 tumours, indicating Lynch syndrome aetiology. Conclusion: Patients with Lynch syndrome carrying an MSH2 mutation are at increased risk of urinary tract cancer including bladder cancer. In these cases surveillance should be considered.

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