Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey.

INTRODUCTION: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe. METHODS: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022. RESULTS: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV. CONCLUSIONS: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed.

A Danish nationwide study of risk factors associated with Type I and Type II endometrial cancer.

OBJECTIVE: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors. METHODS: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade. RESULTS: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors. CONCLUSIONS: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.

Risk of juvenile idiopathic arthritis among children conceived after fertility treatment: a nationwide registry-based cohort study.

STUDY QUESTION: Is the risk of juvenile idiopathic arthritis (JIA) increased in children conceived after fertility treatment, and is an observed association caused by specific types of fertility treatment or by factors associated with the underlying infertility? SUMMARY ANSWER: The risk of JIA in children conceived after fertility treatment (any and specific types of fertility treatment) was not convincingly affected when compared with children born to fertile women. WHAT IS KNOWN ALREADY: It has been suggested that fertility treatment may affect the development of the immune system and thereby increase the risk of developing autoimmune diseases, including JIA. STUDY DESIGN, SIZE, DURATION: This retrospective population-based cohort study included all live-born children in Denmark between 1 January 1996 and 31 December 2012 (n = 1 084 184). The study population was followed from date of birth until first diagnosis of JIA as registered in the Danish National Patient Registry, date of 16th birthday, date of emigration, date of death or end of follow-up (31 December 2014), whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort was linked to the Danish Infertility Cohort in order to identify children born to women with fertility problems (n = 174 702) and fertility treatment (n = 89 931). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During a median follow-up period of 10.3 years, 2237 children were diagnosed with JIA. Children born to women with fertility problems had an increased risk of JIA (HR 1.18, 95% CI 1.05-1.32) compared with children born to fertile women. However, the risk was not increased in children conceived after any fertility treatment (HR 1.11; 95% CI 0.95-1.29), or after specific types of fertility treatment being ART (HR 1.05; 95% CI 0.83-1.33), IVF (HR 1.01; 95% CI 0.73-1.38), ICSI (HR 0.98; 95% CI 0.64-1.50) or any fertility drugs (HR 1.10; 95% CI 0.94-1.28) compared with children born to fertile women. The associations between fertility treatment and JIA were also assessed by using children born to women with fertility problems without fertility treatment in the index pregnancy as a reference group, however, the findings did not change substantially. LIMITATIONS REASONS FOR CAUTION: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of JIA cases. There may be some misclassification of fertility problems, as some women have undiagnosed fertility problems and are therefore not included in the Danish Infertility Cohort; potentially leading to slight attenuation of the association between fertility problems and JIA. WIDER IMPLICATIONS OF THE FINDINGS: The results are based on national data and our findings can therefore be applied to other similar populations. Our results indicate that fertility treatment per se do not increase the risk of JIA but merely that the increased risk of JIA observed among children born to women with fertility problems may be due to underlying factors related to both infertility and JIA. However, as this is the first large study in this field, further studies are needed to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Jascha Foundation, the Aase and Ejner Danielsens Foundation and The Danish Rheumatism Association. All authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

[Guideline for antiretroviral therapy of HIV-infected children and adolescents]. / Leitlinie der Pädiatrische Arbeitsgemeinschaft AIDS (PAAD) e.V. zur antiretroviralen Therapie bei HIV-infizierten Kindern und Jugendlichen (2011).

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different. The above aspects and the decreased number of antiretroviral substances underline the need for specific guidelines for HIV-therapy in children and adolescents. The German Pediatric Working group AIDS (PAAD) has formulated this guideline in 2011 based on new study results, changes in international recommendations and newly available drugs.

[Postnatal therapy for congenital toxoplasmosis: a comparison of 2 different treatment approaches]. / Postnatale Therapie der konnatalen Toxoplasmose: Ein Vergleich zweier unterschiedlicher Vorgehensweisen.

Protocols recommended in the USA and Germany for the postnatal treatment of congenital toxoplasmosis are mainly based on the National Collaborative Chicago-based Congenital Toxoplasmosis Study that calls for daily administration of pyrimethamine in combination with sulfadiazine for several months, then 3 times a week. The recommended total duration of treatment is 12 months. This scheme necessitates frequent white blood cell counts that often result in the discontinuation of treatment because of severe neutropenia even with the concomitant administration of folinic acid. In contrast, the administration of pyrimethamine with sulfadoxine every 2 weeks for 2 years, as used by a referral centre in Toulouse, France, is associated with less toxicity. The efficacy may even be improved, as judged by the rate of new chorioretinal lesions. In the absence of larger randomised studies the Toulouse protocol appears to have several advantages when a decision has to be made to treat infants with congenital toxoplasmosis.

Disease progression in HIV-1 infected children and adolescents--results of a German-Austrian cohort study.

OBJECTIVE: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes. PATIENTS AND METHODS: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes. RESULTS: 174 HIV- infected paediatric patients were followed up in 12 centres in Germany and Austria between 1998 and 2003. Initially 54 (31%) patients had no antiretroviral therapy, 35 (20%) received a two-drug regimen (ART) and 85 patients (49%) a highly active antiretroviral therapy (HAART>or=3 drugs). After an observation period of 5 years, 8 patients (4%) had no therapy, 17 (10%) were on ART and 134 patients on HAART (77%). The number of patients with salvage therapy (>or=4 drugs) increased from 5 (3%) to 15 patients (9%). 72 of 166 treated patients (43%) had no change of their drug regimes, 68 patients (41%) had one change and 26 patients (16%)>or=2 changes. Main reasons for changes were increased viral load (49%), immunologic deterioration (21%) and adverse events (14%). During the follow up period no patient died. According to the CDC classification, disease progression was seen in 48 of 174 patients (28%), of whom 20 had deteriorations of clinical categories (A, B, C) and 28 of immunologic categories. Using Kaplan-Meier curves, the mean time from study onset until change of clinical categories was 61 months for patients on HAART, 26 months for patients on ART and 14 months for patients without ART. CONCLUSION: In paediatric patients with HIV infection, disease progression has declined substantially by introduction of HAART. Superiority of HAART compared with ART was demonstrated. Non-adherence as well as other reasons for treatment failure have to be studied more carefully.

Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children.

OBJECTIVE: To describe the long-term efficacy over 5 years of regimens including combinations of abacavir, lamivudine and/or zidovudine in previously untreated children in the PENTA 5 trial. DESIGN: PENTA 5 was a 48-week randomised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor (NRTI) combinations as part of first triple antiretroviral therapy (ART). METHODS: 128 ART-naïve children were randomised to zidovudine\lamivudine (n = 36), zidovudine\abacavir (45) or lamivudine\abacavir (47). Asymptomatic children (n = 55) were also randomised to nelfinavir or placebo; all other children received open-label nelfinavir. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo. RESULTS: Median follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had changed their randomised NRTIs in the zidovudine\lamivudine, zidovudine\abacavir and lamivudine\abacavir groups respectively, but 18%, 50% and 50% of these changes were either early single drug substitutions for toxicity or switches with viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery). At 5 years, 55%/32% zidovudine\lamivudine, 50%/25% zidovudine\abacavir and 79%/63% lamivudine\abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p = 0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02); weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V). CONCLUSIONS: Five year data demonstrate that lamivudine\abacavir is more effective in terms of HIV-1 RNA suppression and growth changes, with lower rates of switching with detectable HIV-1 RNA than zidovudine\lamivudine or zidovudine\abacavir, and should be preferred as first-line NRTI backbone.

Evaluation of platelet adhesion and activation on polymers: Round-robin study to assess inter-center variability.

The regulatory agencies provide recommendations rather than protocols or standard operation procedures for the hemocompatibility evaluation of novel materials e.g. for cardiovascular applications. Thus, there is a lack of specifications with regard to test setups and procedures. As a consequence, laboratories worldwide perform in vitro assays under substantially different test conditions, so that inter-laboratory and inter-study comparisons are impossible. Here, we report about a prospective, randomized and double-blind multicenter trial which demonstrates that standardization of in vitro test protocols allows a reproducible assessment of platelet adhesion and activation from fresh human platelet rich plasma as possible indicators of the thrombogenicity of cardiovascular implants. Standardization of the reported static in vitro setup resulted in a laboratory independent scoring of the following materials: poly(dimethyl siloxane) (PDMS), poly(ethylene terephthalate) (PET) and poly(tetrafluoro ethylene) (PTFE). The results of this in vitro study provide evidence that inter-laboratory and inter-study comparisons can be achieved for the evaluation of the adhesion and activation of platelets on blood-contacting biomaterials by stringent standardization of test protocols.

Terminal deoxynucleotidyl transferase (TdT) expression in acute myeloid leukemia.

Terminal deoxynucleotidyl transferase (TdT) was initially considered as a marker of immature lymphoid cells, but many studies have since provided conclusive evidence for the existence of TdT+ cases of acute myeloid leukemia (AML). The reported incidence of TdT+ AML cases varies largely (from 0% to 55%, average of combined data of the literature 18%, children 19%, and adults 21%) suggesting interlaboratory differences in the types of AML examined, the sensitivity of the method used, and the percentage of positive blasts taken as cut-off value. Significantly higher frequencies of TdT+ AML were reported in studies employing immunocytochemical staining (alkaline phosphatase anti-alkaline phosphatase or immunoperoxidase) than in series using immunofluorescence microscopy or biochemical assays. Statistical analysis of various cut-off levels demonstrates an inverse correlation between cut-off point and incidence. The combined data show that TdT-positivity is more common in the immature cell types (M0, M1), with no correlation with age or sex. Except for contested suggestions of an association with t(6;9) and t(8;21), no clear relationship between karyotype and TdT status has been documented. Although an association between T-cell receptor or immunoglobulin gene rearrangements and expression of TdT in AML was postulated, subsequent studies could not demonstrate this correlation. There was no significant relationship with other immunophenotypic markers except for CD34 positivity suggesting that the TdT+ cells represent an immature population. The percentage of positive cells was usually lower in AML than in ALL; in most cases only a subpopulation of the AML cells was TdT+. Thus, TdT could be viewed as a marker of hematopoietic immaturity. In about one-half of the studies on adults, TdT expression was reported to indicate a poor prognosis; others did not find any prognostic difference between TdT+ and TdT- AML cases. No correlation between TdT-positivity and prognosis was found in childhood AML.

An effective and safe protocol involving zidovudine and caesarean section to reduce vertical transmission of HIV-1 infection.

OBJECTIVE: To investigate zidovudine prophylaxis with caesarean section to reduce mother-to-infant HIV transmission. INTERVENTIONS: Elective caesarean section before labour, usually at 36-38 weeks of gestation, plus a short oral course of zidovudine, normally starting at week 32, intravenous zidovudine before caesarean section and for 10 days for the neonate (the reduced Berlin regimen). RESULTS: Of 179 mother-infant pairs 104 received no antiretroviral prophylaxis or therapy (control group), 48 received the reduced Berlin prophylaxis regimen, 18 received combination therapy and nine received only part of the prophylaxis regimen. Of the antiretroviral group, 68 were delivered by elective caesarean section. The HIV transmission rate was zero in the antiretroviral group [95% confidence interval (CI) 0-4.7] and 12.6% (6.4-19.0) in the control group. The reduction in vertical transmission was 90% for the Berlin regimen, with an 80 and 70% reduction in risk associated with antiretroviral treatment and caesarean section, respectively. Maternal CD4 cell count but not viral load had some confounding effect on the reduction in risk attributed to caesarean section and the prophylactic regimen. Neonatal haematological abnormalities associated with antiretroviral intervention lasted for up to 7 weeks. Weight and length, although significantly lower at birth, were normal by 6-8 weeks. CONCLUSION: A much reduced three-arm regimen of zidovudine prophylaxis in combination with caesarean section before labour is highly effective in reducing the risk of vertical HIV transmission and is safe for the infant.

Covalently immobilized thrombomodulin inhibits coagulation and complement activation of artificial surfaces in vitro.

Thrombomodulin (TM) serves as the endothelial cell receptor for thrombin and alters its characteristics from pro- to anticoagulant. Additionally, it promotes the formation of activated protein C. We evaluated the conservation of the overall outcome of these functions in recombinant TM linked to artificial surfaces by incubation with human whole blood in vitro. TM was covalently immobilized through poly(ethylene glycol) (PEG) spacers onto thin films of poly(octadecene alt maleic anhydride) covering planar glass substrates. TM binding to the polymer films was achieved after active ester formation at the carboxylic acid terminus of the PEG spacers and thoroughly characterized by HPLC-based amino acid analysis, immunofluorescence and ellipsometry. TM-coated samples were incubated for 3h with freshly drawn whole human blood anticoagulated with heparin (5IU/ml) using in-house developed incubation systems. The substantially reduced activation of blood coagulation (TAT) for TM-coated samples correlates well with the degree of contact activation (bradykinin and FXIIa formation) while no significant effects were observed for the platelet activation (PF4). Further, complement activation (C5a levels), was strongly diminished at the TM-containing surfaces. We conclude that the suggested method for preparation of TM immobilization may serve to prepare model substrates for studies on TM interactions but similarly provides a promising coating strategy for blood contacting medical devices.

In vitro blood compatibility of polymeric biomaterials through covalent immobilization of an amidine derivative.

We present a surface coating with anticoagulant characteristics showing significantly reduced coagulation activation. The synthesis of a monomeric conjugate containing a benzamidine moiety was carried out and its inhibitory activity against human thrombin, the key enzyme of the blood coagulation cascade, was determined using a chromogenic assay. Based on that, low-thrombogenic interfaces were prepared by covalent attachment of this low-molecular weight thrombin inhibitor on poly(octadecene-alt-maleic anhydride) copolymer thin films and characterized using ellipsometry, XPS and dynamic contact angle measurements. The in vitro hemocompatibility tests using freshly drawn human whole blood showed, in agreement with the SEM images, that a PO-MA film modified with a benzamidine moiety using a PEG spacer decreased the activation of coagulation, platelets and the complement system. The decreased protein adsorption, in addition to the specific inhibition of thrombin, effectively enhanced the short-term hemocompatibility characteristics.

Clinical, morphologic, cytogenetic and prognostic implications of CD34 expression in childhood and adult de novo AML.

Expression of CD34 by leukemic blasts was analyzed in 230 pediatric and 251 adult patients with de novo AML enrolled in two large multicenter trials (AML-BFM-87 and AMLCG respectively). The association between CD34 positivity and morphological classification according to FAB criteria, cytogenetic aberrations, immunophenotypic features and clinical characteristics was investigated. CD34 was expressed (> or = 20%) by leukemic cells from 45% of childhood and 43% of adult AML patients. CD34+ AML was often associated with M1/M2 morphology as well as the coexpression of CD7 and TdT. Translocation t(8;21), inv(16) and chromosome 5 and 7 aberrations were more frequently observed in CD34+ AML. There was a low frequency of CD34 expression in infant AML but no age dependency was evident in adult patients. CD34 expression exerted no influence on the rate of complete remissions (CR) after intensive multidrug induction therapy. In adults, 56% of the CD34-positive and 64% of CD34-negative cases achieved CR (P = 0.29), and the childhood trial even revealed a slight advantage for CD34+ AML with a CR rate of 80% vs. 71% for CD34-negative cases (P = 0.068). Long-term follow-up disclosed no significant differences in remission duration or event-free survival between the CD34-positive and CD34-negative groups. In conclusion, CD34+ AML patients comprise a heterogeneous group with good as well as poor risk factors. Though characterized by some distinct features, CD34 lacks prognostic significance in de novo AML patients submitted to intensive polychemotherapy.

Design and evaluation of novel blood incubation systems for in vitro hemocompatibility assessment of planar solid surfaces.

Success in the development of hemocompatible biomaterials depends on adequate equipment and procedures for standardized analysis of blood-materials interactions in vitro. In view of the limited standard of knowledge on that important aspect, two novel incubation systems were designed, built, and evaluated for the in vitro assessment of the hemocompatibility of planar solid surfaces: A screening setup was introduced for the comparison of up to 12 different samples. A perfusion setup was developed to model the directed blood flow in the vascular system during incubation by a recirculation circuit, allowing the variation of the wall shear rate at the sample surface. The incubation procedures utilized freshly drawn, heparinized whole human blood. Hemocompatibility in terms of selected aspects of coagulation, thrombogenicity, and immune responses was quantified through plasma levels of characteristic molecules (immunoassays), cell counting, and analysis of adherent cells and fibrin formation (scanning electron microscopy), respectively. Prevention of blood-air contact and mechanical stress, constant temperature and blood pH during incubation, and the suitable choice of reference materials were found to be crucial for reliable testing. Considering those requirements, screening and perfusion system both provided sensitive discrimination between a given set of planar solid surfaces. In conclusion, the suggested methods for an in vitro hemocompatibility assessment permit versatile, sensitive, and efficient analysis of important blood-material interactions despite the unavoidable variability of blood characteristics in different experiments.

[Morphological, immunological and cytogenetic diagnosis in acute leukemias]. / Morphologische, immunologische und zytogenetische Diagnostik akuter Leukämien.

Current diagnosis of acute leukemia includes traditional morphology and cytochemistry supplemented with immunophenotypic, cytogenetic and molecular biologic analyses. This multiparameter approach has revealed the biological heterogeneity of acute leukemias and has enabled the identification of leukemic syndromes with distinct clinical and biological features. Morphology and cytochemistry are of particular importance for the classification of acute myeloid leukemia, except for certain subtypes such as minimally differentiated acute myeloid leukemia [AML-M0] or acute megakaryoblastic leukemia [AML-M7], requiring additional immunophenotypic or ultrastructural analyses. In acute lymphoblastic leukemia [ALL], immunophenotyping is essential for the diagnosis and lineage assignment [B- and T-lineage ALL] of leukemic blasts. Furthermore, it allows the characterization of the maturation stage and certain subtypes, i.e. ALL with coexpression of myeloid antigens [My+ ALL]. Cytogenetic and molecular analyses of leukemic cells have contributed important informations to the understanding of pathogenetic mechanisms in leukemogenesis and have led to the definition of prognostic risk groups and the development of subtype-specific or risk-adapted therapy strategies.

Does the taking of biopsies affect the metastatic potential of tumours? A systematic review of reports on veterinary and human cases and animal models.

Clinicians and pathologists are sporadically asked by owners whether the taking of tumour biopsies may affect the behaviour of the tumour, including its potential to metastasise. Unfortunately, systematic studies on this subject are unavailable in veterinary medicine, and the aim of this study was to estimate the risk of adverse effects of biopsy taking on tumour progression in animals. A systematic review of veterinary and human case reports and clinical studies as well as experimental animal models of biopsy-induced tumour metastasis was undertaken. There were only two veterinary case reports of needle tract metastases (NTM) following the taking of needle biopsies from urogenital and pulmonary tumours. Seventeen experimental studies found a high incidence of NTM but only a rat osteosarcoma and a hamster squamous carcinoma model showed an increased incidence of distant or regional metastases after incision or excision biopsy. In human medicine, the occurrence of NTM has been reported after the taking of biopsies from mesotheliomas (15%), melanomas (11%) and gall bladder tumours (11%), liver metastases of colon carcinomas (4%) and mammary carcinomas (4%) but an incidence of only <1% for all other tumours. Circulating tumour cells increased immediately after the taking of biopsies from human squamous cell, prostate, breast and hepatocellular carcinomas. Although no increased risk of biopsy-induced distant metastasis has been reported for any type of tumour, this is inconclusive due to a lack of non-biopsied control groups in human studies. Reports of biopsy-induced metastasis in animal tumours indicate that the taking of transcutaneous biopsies from urogenital tumours may be associated with a risk of NTM. However, there is no evidence of a general increase in risk of distant metastases in any tumour type in people or animals. The overall risk therefore appears to be negligible when compared to the valuable information obtained from biopsies in veterinary practice.