J.W. Oosterhuis

Biobanking for interdisciplinary clinical research.

Biobanking nowadays is mostly strongly determined by the specific aims of a research group in charge of the biobank, determining their own standards for the collection and annotation of samples. Often a long period is needed to build up the sample and data collections, especially when long-term follow-up data is required. Such collections need a long-term dedication and proper funding. Neglecting either sample number or annotation can result in insignificant or poor results. However, outcome of translational research does not only depend on the sample quality. In many cases it can also be improved to start the experimental design within a multidisciplinary team composed of clinicians including pathologists, molecular biologists, statisticians, bioinformaticians and tissue resource managers. Such a team, capable of careful evaluation of the numbers needed and which or what part of the samples are to be included, could help in obtaining far better results. Many lines of clinical research could benefit more efficiently from the wealth of information stored in well-preserved disease-oriented tissue sample collections with the proper annotations, when the infrastructure around biobanks and new collection build-up is well organized, standardized and streamlined. Future medical research will refine its scientific questions, demanding even further refinement of corresponding clinical information. In addition, larger sample collections are needed to study for instance multifactorial diseases. Today, the samples are collected for tomorrow, therefore, improvement is needed now in standardization, automated enrichment of annotations from hospital information systems and disease registries, insight in overlapping collections of different forms of tissue banking and cooperation in national and international networks.

Virtual Microscopy in Virtual Tumor Banking

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated virtual microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting biorepositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

TuBaFrost: European Virtual Tumor Tissue Banking

TuBaFrost is a consortium responsible for the task to create a virtual European human frozen tumor tissue bank, composed of high quality frozen tumor tissue collections with corresponding accurate diagnosis stored in European cancer centers and universities, searchable on the Internet, providing rules for access and use and a code of conduct to comply with the various legal and ethical regulations in European countries. Such infrastructure would enlarge tissue availability and accessibility in large amounts of specified or even rare tumor samples. Design of an infrastructure for European residual tissue banking with the described characteristics, clear focus points emerge that can be broken down in dedicated subjects: (1) standardization and quality assurance (QA) to avoid inter-institute quality variation; (2) law and ethics enabling exchange of tissue samples possible between institutes in the different European countries, where law and ethics are characterized by a strong variability; (3) rules for access, with sufficient incentives for collectors; (4) central database application containing innovations on search and selection procedures; (5) support when needed with histology images; and (6) Internet access to search and upload, with in addition a solid website giving proper information on the procedures, intentions and activities not only to the scientific community, but also to the general public. One consortium decision, part of the incentives for collectors, had major impact on the infrastructure; custodianship over the tissues as well as the tissues stay with the collector institute. Resulting in specimens that are not given to an organization, taking decisions on participation of requests, but instead the local collected tissues stay very easy to access by the collector and allows autonomous negotiation between collector and requestor on cooperation, coauthorship in publication or compensation in costs. Thereby, improving availability of large amounts of high quality samples of a highly specified or rare tumor types and contact opportunities for cooperation with other institutes.

Burden of extragonadal germ cell tumours in Europe and the United States

Dear Sirs, We read with interest the recent publication by Trama et al. about the burden of testicular, paratesticular and extragonadal germ cell tumours in Europe in this journal(1). We did comparable analyses based on data from the Surveillance, Epidemiology and End Results (SEER) Program, original nine registries for the years 1973-2007(2). Many statistical figures on extragonadal germ cell tumours (EGCTs) are similar in the U.S. and Europe. For example, we also observed that mediastinal EGCTs had the worst 5-year relative survival (SEER: 58%, Europe: 53%). However, the estimated age-standardized incidence rate of EGCTs is considerably higher in the U.S. than Europe. To quantify this difference, we calculated the ratio of age-standardized incidence rates (SEER estimate, whites, 1997-2007 / European estimate 1995-2002) and corresponding 95% confidence intervals for males and females(3). Among males, the EGCT rate in the U.S. is 1.82 (95%CI: 1.58-2.10) times higher than in Europe. Among females, the EGCT rate in the U.S. is 2.46(95%CI: 1.94-3.12) times higher than in Europe. As rate estimates were quite precise in both regions, random error is an unlikely explanation for this finding. In contrast to Trama et al., we included EGCTs of the placenta (all nondysgerminoma). 312 out of 567 EGCTs among white females (55%) during the period 1973-2007 originated from the placenta. When we exclude placental EGCTs, the age-standardized incidence of EGCT among white females forthe period 1997-2007 decreases to 1.1 per million person-years (standard error [SE]: 0.10) resulting in a US:Europe ratio of 1.59 (95%CI: 1.25-2.02). We provide some hypotheses that might explain these differences. First, EGCTs are only rarely registered and can be easily miscoded as gonadal germ cell tumours if the topography coding of tumours is not intensively monitored. In contrast to the SEER program, the European analysis was based on 64 cancer registries located throughout Europe with varying degrees of quality control and varying degrees of completeness of registration(4).Second, EGCT cancer registry reports that contain only unspecifiedhistology (e.g. carcinoma, not otherwise specified) cannotbe included in the data analysis of EGCTs. A comparison of the number of extragondal tumours with unspecifiedhistologies at typical sites of EGCTs (e.g. mediastinum, pineal gland, retroperitoneum, brain) might give clues to this hypothesis. Finally, different prevalences of the, until now, unknown risk factors of EGCTs in the U.S. and Europe may play a role. Interestingly, in a recent unpublished pooling project of 9 population-based cancer registries in Germany of the years 1998-2008 which included 362,450,458 person-years, we estimated an age-standardized (European standard population) incidence rate for male EGCTs, female EGCTs including placental EGCTs, and female EGCTs excluding placental EGCTs of 1.79 (SE 0.1), 1.14 (SE 0.09), 0.79 (SE 0.08), respectively, which is very much in line with European-wide estimates.