Biomedical subjects

A Spatz

Publications and source records attributed to A Spatz.

At least 19 recordsLinked to original sources

PubMed2006

TuBaFrost 3: regulatory and ethical issues on the exchange of residual tissue for research across Europe.

The regulatory regimes for research with residual tissue and accompanying data differ widely between countries in the European Union (EU): from specific consent to opt-out or even no consent at all. This could greatly hamper research where the exchange of tissue and accompanying data has become the gold standard, like in TubaFrost. Instead of adhering to international guidelines, which have a democratic deficit, or an attempt for a new set of possible harmonising rules, TubaFrost chose to create a coordinating rule: if tissue may legitimately be used for a certain kind of research in the country where it was taken and under whose jurisdiction the patient falls, it may also be used for such research in the country where it is sent to in the context of a scientific program even if in that other country other regulations would apply for research with residual tissue taken from patients under their jurisdiction. This coordinating rule has a sound basis in EU law in general and will solve the problems related to diverging national regulatory regimes in the case of cross national research with residual tissue.

Ethics, Research↗

PubMed2006

TuBaFrost 5: multifunctional central database application for a European tumor bank.

Developing a tissue bank database has become more than just logically arranging data in tables combined with a search engine. Current demand for high quality samples and data, and the ever-changing legal and ethical regulations mean that the application must reflect TuBaFrost rules and protocols for the collection, exchange and use of tissue. To ensure continuation and extension of the TuBaFrost European tissue bank, the custodianship of the samples, and hence the decision over whether to issue samples to requestors, remains with the local collecting centre. The database application described in this article has been developed to facilitate this open structure virtual tissue bank model serving a large group. It encompasses many key tasks, without the requirement for personnel, hence minimising operational costs. The Internet-accessible database application enables search, selection and request submission for requestors, whereas collectors can upload and edit their collection. Communication between requestor and involved collectors is started with automatically generated e-mails.

Computer Simulation↗

PubMed2006

TuBaFrost 2: Standardising tissue collection and quality control procedures for a European virtual frozen tissue bank network.

Tumour Bank Networking presents a great challenge for oncological research as in order to carry out large-scale, multi-centre studies with minimal intrinsic bias, each tumour bank in the network must have some fundamental similarities and be using the same standardised and validated procedures. The European Human Frozen Tumour Tissue Bank (TuBaFrost) has responded to this need by the promotion of an integrated platform of tumour banks in Europe. The operational framework for TuBaFrost has drawn upon the best practice of standard workflows and operating procedures employed by members of the TuBaFrost project and key initiatives worldwide.

Biological Specimen Banks↗

PubMed2006

TuBaFrost 4: access rules and incentives for a European tumour bank.

When designing infrastructure for a networked virtual tumour bank (samples remain at the collector institutes and sample data are collected in a searchable central database), it is apparent that this can only function properly after developing an adequate set of rules for use and access. These rules must include sufficient incentives for the tissue sample collectors to remain active within the network and maintain sufficient sample levels in the local bank. These requirements resulted in a key TuBaFrost rule, stating that the custodianship of the samples remains under the authority of the local collector. As a consequence, the samples and the decision to issue the samples to a requestor are not transferred to a large organisation but instead remain with the collector, thus allowing autonomous negotiation between collector and requestor, potential co-authorship in publications or compensation for collection and processing costs. Furthermore, it realises a streamlined cost effective network, ensuring tissue visibility and accessibility thereby improving the availability of large amounts of samples of highly specific or rare tumour types as well as providing contact opportunities for collaboration between scientists with cutting edge technology and tissue collectors. With this general purpose in mind, the rules and responsibilities for collectors, requestors and central office were generated.

Europe↗

PubMed2006

TuBaFrost 1: Uniting local frozen tumour banks into a European network: an overview.

TuBaFrost is the consortium responsible for the creation of a virtual European human frozen tumour tissue bank: a collection of high quality frozen residual, accurately classified tumour tissue samples, which are stored in European cancer centres and universities. This virtual tissue bank, searchable on the internet, has rules for access and use, and a code of conduct to comply with the various legal and ethical regulations in European countries. The easy accessibility and the European scale of the bank will result in the availability of a large number of samples even of rarer tumour types. Standardisation of collection, storage and quality control throughout the network is achieved minimising inter-institutional variability. A website providing access to upload, search and request samples is a key tool of the tissue bank. The search engine makes use of virtual microscopy. An overview of the development of the European virtual frozen tissue bank infrastructure is described in this paper. The various key aspects are described in more detail in a series of articles to appear in this Journal.

Biological Specimen Banks↗

PubMed2006

TuBaFrost 6: virtual microscopy in virtual tumour 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 bio-repositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Computer Simulation↗

PubMed2006

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.

Databases, Factual↗

PubMed2006

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).

Databases, Factual↗

PubMed2006

Skin cancer incidence and survival in European children and adolescents (1978-1997). Report from the Automated Childhood Cancer Information System project.

Patterns and trends of melanoma and skin carcinoma incidence and survival of European children (age 0-14 years) and adolescents (age 15-19 years) were investigated. Between 1978 and 1997, a total of 1419 melanoma and 485 skin carcinoma cases were recorded in the cancer registries contributing to the Automated Childhood Cancer Information System (ACCIS) study. During 1988-1997, the incidence of melanoma was 0.7 per million children and 12.9 per million adolescents; corresponding rates for skin carcinomas were 0.3 and 3.7 per million, respectively. The British Isles had the highest incidence of skin cancers in children and adolescents. For Europe, in adolescents melanomas were more common in the North and West, skin carcinomas in the South and East. Between 1978 and 1997 incidence increased annually in adolescents, by 4.1% for melanoma and 2.5% for skin carcinoma. Differences in aetiology between childhood and adolescent skin cancers cannot be excluded. Survival was relatively high and the geographical variations in incidence and survival seem to be associated.

Adolescent↗

PubMed2006

[Clinical and genetic study in 22 patients with basal cell nevus syndrome].

BACKGROUND: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by developmental abnormalities and cancer predisposition. The PTCH 1 gene, the human homolog of the Drosophila segment polarity gene patched, has been shown to be involved in the development of nevoid basal cell carcinoma syndrome. PTCH 1 is mapped to chromosome 9q22.3. The aim of the present study was to report on clinical and genetic characteristics in patients followed for nevoid basal cell carcinoma syndrome and to compare them to the data in the literature. PATIENTS AND METHODS: Screening for PTCH 1 mutations was done in 22 patients followed between 1981 and 2003 for clinical suspicion of nevoid basal cell carcinoma syndrome. Clinical and radiological data were reviewed retrospectively from records. Genetic analysis was performed using blood samples after patient informed consent was obtained. When possible, DNA was also analyzed from the parents of patients in whom PTCH 1 mutations were found. RESULTS: All patients had developed basal cell carcinomas: 45% palmar and plantar pitting, 62% jaw cysts and 66% calcification of falx cerebri. Medulloblastomas and meningiomas were the most common associated tumors. PTCH 1 mutations were identified in 13 patients: 6 familial cases, 3 sporadic cases and for 4 patients, it was not possible to conclude. Nine different new germ-line mutations were identified. DISCUSSION: Genetic analysis allows molecular confirmation of diagnosis in about half of all patients. Early diagnosis is essential for detection of clinical and radiological manifestations in young patients and for provision of advice concerning protection of the skin from the sunlight.

Adolescent↗

PubMed2006

[Melanoma within naevus spilus: 5 cases].

BACKGROUND: Nevus spilus is defined as café-au-lait macules with dark maculopapular speckles. Histologically, it has the aspect of lentigo associated with nevocellular nevus. There are 3 types of nevus spilus: small or medium-sized (<20 cm), giant and zosteriform. Malignant transformation of nevus spilus is rare. PATIENTS AND METHODS: We analyzed the cases of 5 patients presenting melanoma within nevus spilus as well as 20 published cases. The evaluation criteria were: for nevus spilus: size, type, topography, age of onset and presence of dysplastic nevi within the nevus spilus; for melanoma: clinical aspect, histological type, thickness, level and age at diagnosis. The presence of other risk factors for melanoma was noted. RESULTS: The 14 women and 11 men had a mean age of 49 years at melanoma diagnosis. Type of nevus spilus was: small or medium-sized (15 cases), zosteriform (6 cases) and giant (4 cases). Only 3 nevi spili were<4 cm in diameter. Nevus spilus was present since birth (11 cases), childhood (7 cases), after the age of 20 years (3 cases) and was unspecified in 4 cases. Three of our five patients had other risk factors for melanoma. Two patients were presenting 2 melanomas within nevus spilus. The histological type of melanoma was not specified in 8 cases but SSM was the most common type (13 cases). Median Breslow thickness was 1.25 mm (0.27 to 8 mm) for the 19 cases in which it was specified. CONCLUSION: The following criteria appeared to be associated with risk of developing melanoma in nevus spilus patients: nevus spilus present since birth, nevus spilus over 4 cm in diameter, and giant or zosteriform nevus spilus. Development of melanoma within nevus spilus is a rare event. Consequently, guidelines for follow-up of nevus spilus cannot be defined. However, follow-up is recommended, and in particular, self-examination.

Adult↗

PubMed2006

Microcystic adnexal carcinoma: report of seven cases including one with lung metastasis.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm, with a high rate of local recurrences. OBJECTIVE: A series of MAC was analyzed and compared to previously published cases. METHODS: Seven cases of MAC were identified in the register of the institution. Medical and pathological records were reviewed. RESULTS: The primary MAC were located on the face in all patients, and 85% were initially misdiagnosed. The mean follow-up duration was 108 months. The recurrence rate was high: 4 patients developed recurrences. In 3 patients, the course of the disease was severe: one of them developed pathologically proven lung metastasis. CONCLUSION: The present study and review of the literature confirm the clinically aggressive evolution of MAC and its rare ability to give rise to metastasis. Long-term clinical follow-ups with imaging investigations are mandatory.

Adult↗

PubMed2005

Comprehensive analysis of CDKN2A (p16INK4A/p14ARF) and CDKN2B genes in 53 melanoma index cases considered to be at heightened risk of melanoma.

OBJECTIVE: Comprehensive analysis of the 9p21 locus including the CDKN2A, ARF, and CDKN2B genes in 53 individuals from melanoma index cases considered to be at heightened risk of melanoma. METHODS AND RESULTS: Using a combination of DNA sequencing, gene copy number by real time quantitative PCR, linkage analysis, and transcript analysis in haploid somatic cell hybrids, we found no evidence for germline alteration in either coding or non-coding domains of CDKN2A and CDKN2B. However, we identified a p14ARF exon 1beta missense germline mutation (G16D) in a melanoma-neural system tumour syndrome (CMM+NST) family and a 8474 bp germline deletion from 196 bp upstream of p14ARF exon 1beta initiation codon to 11233 bp upstream of exon 1alpha of p16(INK4A) in a family with five melanoma cases. For three out of 10 families with at least three melanoma cases, the disease gene was unlinked to the 9p21 region, while linkage analysis was not fully conclusive for seven families. CONCLUSIONS: These data reinforce the hypothesis that ARF is a melanoma susceptibility gene and suggest that germline deletions specifically affecting p14ARF may not be solely responsible for NST susceptibility. Predisposition to CMM+NST could either be due to complete disruption of the CDKN2A locus or be the result of more complex genetic inheritance. In addition, the absence of any genetic alteration in 50 melanoma prone families or patients suggests the presence of additional tumour suppressor genes possibly in the 9p21 region, and on other chromosomes.

Cell Line, Tumor↗

PubMed2004

Surgical procedure in patients with ovarian cancer diagnosed at the time of prophylactic oophorectomy. Analysis of two cases, literature review and surgical implications.

The aim of this study was to discuss the surgical management for ovarian or tubal cancers diagnosed at the time of prophylactic oophorectomy. Two patients with BRCA1 & BRCA2 mutations carriers had ovarian cancer diagnosed during laparoscopic oophorectomy. Conversion to laparotomy was performed in order to complete surgery (hysterectomy, multiple peritoneal biopsies, omentectomy, pelvic and para-aortic lymphadenectomy). These two patients were upstaged on the basis of para-aortic lymphadenectomy and had massive nodal spread into para-aortic area. One of them had no intra-peritoneal disease and the other one had minor peritoneal disease (only one positive pelvic biopsy in the Douglas pouch). These two patients are alive, one of them with 3.5 years of follow-up after the end of adjuvant treatment. In order to ensure the exact spread of the disease. Lymphadenectomy should be performed in patients with ovarian cancer diagnosed at the time of prophylactic surgery.

BRCA1 Protein↗

PubMed2003

In vivo evolution of tumour cells after the generation of double-strand DNA breaks.

In vitro, the ratio of single- to double-strand DNA breaks (DSB) and their absolute values determine the cell death pathway. The consequences of the generation of various numbers of DSB generated in vivo in tumour cells have been analysed in two different experimental tumour models. Synchronisation of DSB generation and control of their number have been achieved using different doses of bleomycin (BLM) and tumour cell permeabilisation by means of locally delivered electric pulses. According to BLM dose, different cell death pathways are observed. At a low therapeutic dose, a mitotic cell death pathway is detected. It is characterised by the appearance of 'atypical mitosis', TUNEL and caspase-3 positive, 24 h after the treatment, and later by the presence of typical apoptotic figures, mainly TUNEL positive but caspase-3 negative. Caspase-3 is thus an early marker of apoptosis. Mitotic cell death is also followed by lymphocytic infiltration reaction. At high doses of BLM, pseudoapoptosis is detected within a few minutes after the treatment. These cell death pathways are discussed as a function of the number of DSB generated, by comparison with previous results obtained in vitro using BLM or ionising radiation.

Animals↗

PubMed2003

Interobserver reproducibility of ulceration assessment in primary cutaneous melanomas.

In the recently revised melanoma staging system proposed by the American Joint Committee on Cancer (AJCC), ulceration assessment by the pathologist is a pivotal parameter. Patients upstaged because of ulceration might be included in adjuvant trials conducted in AJCC stage II melanoma patients. Therefore, accuracy based on interobserver reproducibility for melanoma ulceration assessment is crucial for proper clinical management. In some cases, it is extremely difficult, even for an experienced pathologist, to distinguish between trauma-induced ulceration, artifact and tumoral ulceration. Whether this difficulty may be resolved by the use of a more precise definition of ulceration has not been evaluated. Therefore, we have proposed a refined definition of melanoma ulceration and we tested whether this definition might improve the interobserver interpretative reproducibility of ulceration in primary cutaneous melanomas. The results of this study support the need for a more precise definition of melanoma ulceration that rules out biopsy trauma or processing artifact and could be incorporated into a standardised pathology worksheet for reporting primary melanomas.

Biopsy↗

PubMed2003

Human tissue research: EORTC recommendations on its practical consequences.

Improvement in cancer care is possible by applying new treatment modalities, which are emerging from knowledge and discoveries coming from laboratory research. This is possible through international collaboration and the collection of tumour tissues. Creation of a European Organisation for Research and Treatment of Cancer (EORTC) Tumor Bank is a natural step in this direction, by offering tumour sample collection from patients entered in EORTC trials. The aim of such a bank is not only to improve the diagnostic review process, but also to facilitate translational research by allowing clinicians and basic scientists to enter into close collaborations. The EORTC Tissue Research Policy is developed to assure, under the EORTC legal framework, an ethical and scientific review of research projects, guarantee adequate information is given to patients, establish procedures on the use of materials, including legal aspects, and publication policies. Being part of the EU TubaFrost project, the EORTC will provide a common international platform for the use of tissues for research purposes, finding a balance between different laws and assuring scientific progress.

Clinical Trials as Topic↗

PubMed2003

[Significance of sentinel lymph node biopsy in Merkel cell carcinoma. Analysis of 11 cases].

BACKGROUND: Merkel cell carcinoma is an aggressive cutaneous neoplasm with a high propensity for nodal metastases. Regional lymph node involvement develops in 45 to 65 p. 100 of patients. We evaluated in Merkel cell carcinoma the use of sentinel lymph node biopsy which allows the identification of occult nodal metastases. PATIENTS AND METHODS: Eleven patients diagnosed with Merkel cell carcinoma without clinical nodal involvement underwent pre-operative lymphoscintigraphy followed by sentinel lymphadenectomy with histologic analysis. Identification of microscopic nodal metastases led to complete lymph node dissection and adjuvant radiation therapy to the lymph node basin. RESULTS: The sentinel lymph node was successfully identified in 9 patients. Two patients demonstrated metastatic disease in their sentinel lymph nodes. At subsequent complete node dissection, one of two patients had an additional metastatic lymph node. None of the eleven patients experienced recurrent disease at a follow-up varying from 1 to 42 months. One patient with a negative sentinel lymph node experienced lymphoedema. COMMENTS: Our results are consistent with the 14 published studies which totalled 93 patients with Merkel cell carcinoma and identified 29 patients (30 p. 100) with nodal involvement. Metastatic disease was identified only after immunohistochemical analysis in 20 p. 100 of these patients (n=6). Lymph node involvement appears to be a bad prognostic factor with 29.6 p. 100 of disease recurrence, as opposed to 3 p. 100 in patients with an uninvolved sentinel lymph node. Although the prognostic significance of this technique seems interesting, there is no optimal therapeutic approach to sentinel lymph node involvement.

Adult↗