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In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ̃50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements. © The Author 2012. Published by Oxford Univer

Purpose: To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods: Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m2 in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results: Accrual was from November 1998 to April 2009. A total of 169patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion: T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible pati

This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy., Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H. Extramural, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Testicular cancer (TC) is usually diagnosed after manifestation of an overt tumour. Tumour formation is preceded by a pre-invasive and asymptomatic stage, carcinoma in situ (CIS) testis, except for very rare subtypes. The CIS cells are located within seminiferous tubules but can be exfoliated and detected in ejaculates with specific CIS markers. We have built a high throughput framework involving automated immunocytochemical staining, scanning microscopy and in silico image analysis allowing automated detection and grading of CIS-like stained objects in semen samples. In this study, 1175 ejaculates from 765 subfertile men were tested using this framework. In 5/765 (0.65%) cases, CIS-like cells were identified in the ejaculate. Three of these had bilateral testicular biopsies performed and CIS was histologically confirmed in two. In total, 63 bilateral testicular biopsy were performed in conjunction with analysis of the ejaculates because of infertility work-up. Histological analysis of the biopsies for the presence of CIS yielded a test sensitivity of 0.67 and a specificity of 0.98. In addition, ejaculates from 45 patients with clinical signs of an overt TC were investigated and yielded a slightly lower sensitivity (0.51), possibly because of obstruction. We conclude that this novel non-invasive test combining automated immunocytochemistry and advanced image analysis allows identification of TC at the CIS stage with a high specificity, but a negative test does not completely exclude CIS. On the basis of the results, we propose that the assay could be offered to subfertile men and other patients who are at increased risk of TC.

Background. The present study was conducted to evaluate the efficacy and toxicity of a combination of paclitaxel, cisplatin and gemcitabine in patients with carcinoma of unknown primary site (CUP). Patients and methods. Patients with CUP, ECOG performance status 0-1 and age between 18 and 65 years old were treated with paclitaxel 175 mg/m

This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer., Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathic disease. TTP is due to reduced activity of the von Willebrand factor which cleaves ADAMTS13. The disease is characterized by thrombocytopenia (<20 billion/l) intravascular Coombs-negative haemolysis and schistocytes in blood smears. Determination of the ADAMTS13-activity is now becoming available as a routine analysis. We present two cases that illustrate the multi-facetted clinical presentation under which TTP occurs. The importance of access to ADAMTS13 measurements is stressed Udgivelsesdato: 2009/1/26

Item does not contain fulltext, OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Udgivelsesdato: 2008-Nov, BACKGROUND: A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence of the common 10-CAG-long POLG allele with testicular cancer as well as previously reported in some European populations' association with male subfertility, which is a condition carrying an increased risk of TGCT. PATIENTS AND METHODS: The number of CAG repeats in both POLG alleles was established in 243 patients with TGCT and in 869 controls by the analysis of the genomic DNA fragment. RESULTS: A significantly higher proportion of men homozygous allele of other than the common 10 CAG repeats was found among the patients with TGCT in comparison to the controls (4.9% versus 1.3%, respectively, P = 0.001). The vast majority of the homozygous patients had a seminoma (11 of 12; 97%), despite that only about half (55%) of the studied patients had this tumour type. CONCLUSIONS: The findings indicate that the POLG polymorphism may be a contributing factor in the pathogenesis of TGCT particularly in seminoma, but the mechanisms remain to be elucidated.

Unknown primary tumour (UPT) is defined as a histologically confirmed metastatic malignancy for which no primary site has been detected. It accounts for approximately 3-5% of all malignant neoplasms. UPT represents a group of heterogeneous cancers with rapid progression and random, atypical metastases. This article describes the diagnostic strategies, treatment, prognosis and survival of patients with UPT Udgivelsesdato: 2008/11/24

BACKGROUND: Small-cell lung cancer (SCLC) accounts for 15%-20% of all lung cancer cases. Accurate and fast staging is mandatory when choosing treatment, but current staging procedures are time consuming and lack sensitivity.PATIENTS AND METHODS: A prospective study was designed to examine the role of combined positron emission tomography/computed tomography (PET/CT) compared with standard staging (CT, bone scintigraphy and immunocytochemical assessment of bone marrow biopsy) of patients with SCLC. Thirty-four consecutive patients were included. Twenty-nine patients received initial PET/CT.RESULTS: PET/CT caused change of stage in 5/29 (17%). Excluding patients with unconfirmed findings or pleural effusion, the sensitivity for accurate staging of patients with extensive disease was the following: for standard staging 79%, PET 93% and PET/CT 93%. Specificity was 100%, 83% and 100%, respectively.CONCLUSION: The results from this first study on PET/CT in SCLC indicates that PET/CT can simplify and perhaps even improve the accuracy of the current staging procedure in SCLC. A larger clinical trial, preferably with consequent histological confirmation in case of discordance, however, is warranted.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Udgivelsesdato: 2003-Mar, Relapse occurs in 30% of patients with stage I non-seminomatous germ cell tumours (NSGCT) within 1 year after orchiectomy. Whole-body positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) may detect small metastases when standard staging with computed tomography (CT) and tumour markers is negative. In this study, 46 patients underwent FDG-PET after staging with normal CT and tumour markers. To exclude diagnostic test bias and workup bias, all patients had routine follow-up with repeated CT and tumour marker evaluation, even though the initial FDG-PET was positive. Thirty-six patients have remained disease free with a median follow-up of 48 months (range 24-76). Ten patients (22%) suffered disease relapse after a median of 2 months (range 1-8), and of these, seven had a true positive initial PET with increased uptake of FDG indicating metastatic disease. There were three false negative and no false positive PET scans. The sensitivity, specificity and accuracy of PET were 70%, 100% and 93%, respectively. The sensitivity of detecting small retroperitoneal metastases was 88%. The negative and positive predictive values were 92% and 100%, respectively, whereas the negative predictive value of standard staging procedures was 78%. FDG-PET thus seems to be superior to conventional staging (P=0.06) in stage I NSGCT. This non-invasive method may improve the overall management of patients with NSGCT.