Investigating the functionalization of liposomes with NFL-TBS. 40-63 peptide as a promising drug delivery system.

The NFL-peptide was discovered almost 20 years ago, and its targeting properties were assessed alone or in combination with lipid nanocapsules (LNC), magnetic porous silicon nanorods, or gold nanoparticles. Results highlighted a better targeting of cancer cells, in particular glioblastoma and pancreas cancer. Considering the large use of liposomes (LPs) as an hydrophilic drug delivery system, this study explored the possibility to functionalize liposomes with three different sequences of NFL-peptides: native (NFL-peptide), biotinylated (BIOT-NFL) and coupled to fluorescein (FAM-NFL). Dynamic Light Scattering (DLS) complemented by cryo-electron microscopy (CEM) showed a peculiar ultrastructural arrangement between NFL-peptides and liposomes. Based on this architectural interaction, we investigated the biological contribution of these peptides in LPs-DiD glioblastoma cellular uptake. Flow cytometry complemented by confocal microscopy experiments demonstrated a consequent and systematic increased uptake of LPs-DiD into F98 cells when their surface was decorated with NFL-peptides. The intra-cellular distribution of these liposomes via an organelle tracker indicated the presence of LPs-DiD in lysosomes after 4 h. Based on the properties of this NFL-peptide, we showed in this work the crucial role of NFL peptide as an effective and promising actor to potentiate nanoparticles entry in glioblastoma cell lines.

Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10-4 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

Characterization and quantification of the interaction between the NFL-TBS.40-63 peptide and lipid nanocapsules.

Several studies previously showed that the NFL-TBS.40-63 peptide (NFL-peptide) is capable to specifically penetrating several glioblastoma cell lines (rat, mouse, human) and inhibiting their cell division in vitro and their tumor development in vivo. When lipid nanocapsules (LNCs) are functionalized with the NFL-peptide, their absorption is targeted in glioblastoma cells both in vitro and in vivo. In the present study, we investigated the molecular architecture of these nanovectors (LNC-NFL) by using several microscopy techniques (transmission electron microscopy, cryo-electron microscopy, and cryo-electron tomography). We also used high-performance liquid chromatography (UPLC) technique to evaluate the interaction between LNCs and peptides. The work shows that the NFL-peptide forms stable long filaments along which the lipid nanocapsules interact strongly to form some sort of nanomolecular bracelets. This new construction composed of the NFL-peptide and lipid nanocapsules shows a better internalization in rat glioblastoma cells (F98 cells) than lipid nanocapsules alone.

[Pheochromocytomas and paragangliomas in pregnancy: About four cases and key messages on management]. / Phéochromocytomes et paragangliomes pendant la grossesse : à propos de quatre cas et messages clés sur la prise en charge.

OBJECTIFS: The diagnosis of a pheochromocytoma or paraganglioma secreting during pregnancy is a rare and serious situation, involving maternal-fetal prognosis. The purpose of this case series is to discuss the management of these patients. METHODS: This is a retrospective study of cases of pheochromocytoma (n=2) or paraganglioma (n=2) managed during pregnancy between 2013 and 2020 in one center (Lille, France). RESULTS: We report four cases of patients with a diagnosis of pheochromocytoma or paraganglioma during pregnancy, at respectively 4, 28, 31 and 34 weeks of amenorrhea (AS). Their pregnancies were affected by a sudden onset of hypertension sometimes associated with headaches, sweating, and palpitations. All patients delivered by Caesarean section after calcium channel blocker impregnation, with a good outcome. Tumor removal took place at a distance from delivery for each patient. CONCLUSIONS: The therapeutic strategy includes antihypertensive treatment with calcium channel blockers or alphablockers and surgical curative treatment linked to gestational age. Multidisciplinary management as well as early diagnosis can improve the maternal-fetal prognosis. The preferred way of delivery is Caesarean section, but vaginal delivery can also be considered. Removal should ideally take place at a distance from the birth. The analysis of these cases has led to the development of a protocol for monitoring and management of parturients with diagnosis of pheochromocytoma or paraganglioma during pregnancy.

Career aspirations among specialty residents in France: a cross-sectional gender-based comparison.

BACKGROUND: Most studies evaluating career aspirations among gender are performed in Anglo-Saxon countries. Two recent French studies looked at the career choice of residents in obstetrics & gynecology. It seemed useful to us to broaden this questioning to other specialties, by proposing a study to all residents in the same Faculty. The objective of our study was to describe residents' career aspirations and possible barriers according to gender. METHODS: Declarative cross-sectional survey, using questionnaires sent by email to the specialty residents of the Faculty of Medicine of Lille (France). An analysis by specialty group (i.e., medicine, surgery, obstetrics & gynecology, and anesthesia & resuscitation) and a comparison of the results according to gender were performed. RESULTS: Of the 1384 specialty residents currently in training, 462 answered the questionnaire (33.38%), among whom 289 women and 173 men (average age = 27.08 ± 0.091 years). Seventeen women (5.9%) were currently considering a university hospital career versus 37 men (21.4%) (p = 0.001). Gender analysis made it possible to identify obstacles to engaging in a university career: lacking a female model, more frequent doubting the ability to undertake this type of career among women (61.6%) than men (35.3%) (p < 0.001), and gender discrimination felt in the workplace for 51.6% of women (versus 7.5% of men, p < 0.001). Subgroup analysis showed specificities related to each specialty. CONCLUSIONS: Few residents plan to embark upon a university hospital career, let alone female residents. There are considerations specific to each specialty and marked gender differences regarding career aspirations. Many features have been identified as obstacles to access to university hospital positions for women. It is important to develop strategies to remove these barriers and enable women to pursue such university careers. TRIAL REGISTRATION: Not applicable (no intervention).

High incidence of Epstein-Barr virus, cytomegalovirus, and human-herpes virus-6 reactivations in critically ill patients with COVID-19.

BACKGROUND: Systemic reactivation of herpesviruses may occur in intensive care unit (ICU) patients and is associated with morbidity and mortality. Data on severe Coronavirus disease-19 (COVID-19) and concomitant reactivation of herpesviruses are lacking. METHODS: We selected patients admitted to ICU for confirmed COVID-19 who underwent systematic testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human-herpes virus-6 (HHV-6) DNAemia while in the ICU. We retrospectively analysed frequency, timing, duration and co-occurrence of viral DNAemia. RESULTS: Thirty-four patients were included. Viremia with EBV, CMV, and HHV-6 was detected in 28 (82%), 5 (15%), and 7 (22%) patients, respectively. EBV reactivation occurred early after ICU admission and was associated with longer ICU length-of-stay. CONCLUSIONS: While in the ICU, critically ill patients with COVID-19 are prone to develop reactivations due to various types of herpesviruses.

[In Poitou-Charentes family planning centers, Chlamydia trachomatis infection in women is more frequently detected through the presence or absence of risk factors than in accordance with official guidelines]. / Dépistage de l'infection à Chlamydia trachomatis chez les femmes, une pratique qui ne suit pas les recommandations ­ une étude dans les centres de planification de Poitou-Charentes.

BACKGROUND: The French health authorities recommend systematic screening for Chlamydia trachomatis (Ct) urogenital infections in dedicated sexual health centers (planning centers) for women under 25 years old and for women who have changed partners during the last year. The two main purposes of this study were to assess adherence to this recommendation in planning centers and to identify possible obstacles to this screening. METHODS: We conducted an observational prospective study from April to August 2013 in planning centers of Poitou-Charentes. Data on declarative screening practices and possible obstacles to Ct screening were collected qualitatively. Real center practices were also recorded to assess conformity with guidelines. Quantitative data were collected about real activities in each center. Screening percentage among women younger than 25 years and among those who had changed partners during the year was computed for each center. The main endpoint was percentage of centers that did not follow the recommendations. Declared practices were compared to observational practices using real practices data. RESULTS: Twelve out of 17 planning centers in the region participated. Six centers declared they performed systematic screening for Ct infection in women under 25 and 2 centers in women who had changed partners during the year. No center fully complied with the recommendations. Forty-three percent (601/1390) of women with standard screening criteria were screened and 52 % (102/197) of women without these criteria were screened. Depending on the center, declared practices could overestimate or underestimate the observed practices. The declared obstacles were lack of time, patient refusal, budget issues and no specific organization. CONCLUSION: Poitou-Charentes planning centers screen for Ct infection in women younger than 25 years old and those who have changed partners during the last year depending on risk factors (unprotected sex, infected partner…). Which patients need this screening has to be clarified.

[Pseudo-adult Still's disease, anasarca, thrombotic thrombocytopenic purpura and dysautonomia: An atypical presentation of multicentric Castleman's disease. Discussion of TAFRO syndrome]. / Pseudo-maladie de Still, anasarque, microangiopathie thrombotique et dysautonomie : présentation atypique d'une maladie de Castleman multicentrique. Discussion du syndrome TAFRO.

INTRODUCTION: Multicentric Castleman's disease can mimic adult-onset Still disease. It is exceptionally associated with anasarca, thrombotic microangiopathy and dysautonomia. CASE REPORT: We report a 32-year-old woman with an association of oligoanuria, anasarca, thrombotic microangiopathy with features compatible with adult-onset Still disease. The outcome was initially favorable with corticosteroids, immunoglobulins and plasmapheresis but with the persistence of relapses marked by severe autonomic syndrome and necessity of high dose corticosteroids. The diagnosis of mixed type Castleman's disease, HHV8 and HIV negative, was obtained four years after the onset of symptoms by a lymph node biopsy. The outcome was favorable after tocilizumab and corticosteroids but tocilizumab had to be switched to anakinra to ensure a proper and long-lasting control of the disease. CONCLUSION: Our patient partially fits the description of TAFRO syndrome (Thrombocytopenia, Anasarca, myeloFibrosis, Renal dysfunction, Organomegaly), a MCM rare variant, recently described in Japanese patients.

Prognosis of neutropenic patients admitted to the intensive care unit.

PURPOSE: The prognosis of critically ill cancer patients has improved recently. Controversies remain as regard to the specific prognosis impact of neutropenia in critically ill cancer patients. The primary objective of this study was to assess hospital outcome of critically ill neutropenic cancer patients admitted into the ICU. The secondary objective was to assess risk factors for unfavorable outcome in this population of patients and specific impact of neutropenia. METHODS: We performed a post hoc analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centers in France and Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm(3). RESULTS: Among the 1,011 patients admitted into the ICU during the study period 289 were neutropenic at the time of admission. Overall, 131 patients died during their hospital stay (hospital mortality 45.3 %). Four variables were associated with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75-8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51-12.32), microbiological documentation (OR 2.33; CI 1.27-4.26), and need for renal replacement therapy (OR 2.77; 95 % CI 1.34-5.74). Two variables were associated with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1-0.52) and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15-0.9). A case-control analysis was also performed with patients of the initial database; after adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 % CI 0.86-1.89). CONCLUSION: Hospital survival was closely associated with younger age and neutropenic enterocolitis. Conversely, need for conventional MV, for renal replacement therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) were associated with poor outcome.

[Setting-up and evaluation of an educational program for the teaching of breast and pelvic examination in undergraduate medical students: the "PRESAGE" simulation center experience of the medicine university of Lille, France]. / Mise en place et évaluation d'un apprentissage par simulation des examens gynécologiques.

OBJECTIVES: To report the setting-up of a new educational program in the teaching of female pelvic and breast examinations and to investigate and compare the views and experience of undergraduate medical students and teachers on the program. PATIENTS AND METHODS: Prospective evaluation of the teaching program through completion of a satisfaction questionnaire including items related to the educational value of the session by the students and the teachers. RESULTS: The educational program included an online preparation for the session, 3 workshops on training models (breast examination, pelvic examination, cervical snear procedure) and a video clip. In total, 419 (80.6%) of 520 second study year students (and 15 [50%] of 30 teachers [13 doctors and 17 midwifes] responded to the questionnaire). The students and the teachers were either very satisfied (56.6% and 13.4%, respectively) or satisfied (43.2% and 86.6%, respectively). On average, 89.7% of students wanted more lessons of this type and all teachers felt these useful or very useful training for students. DISCUSSION AND CONCLUSION: Teaching sessions for pelvic and breast examination, which make combined use of videos and training models, are associated with a high degree of satisfaction from teachers and students in their second student's year.

Relapsing lymphomatoid papulosis after allogenic bone-marrow transplant.

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder in children, which can rarely be associated with a cutaneous or systemic lymphoma. We report a 13-year-old girl who presented with typical LyP and pathological features of subtype A. Six months later, the patient presented with rapidly progressive peripheral and systemic lymphadenopathy. On examination of a lymph-node biopsy, a lymphoid infiltrate negative for anaplastic lymphoma kinase (ALK) and positive for CD30 was found, suggestive of systemic anaplastic large T-cell lymphoma (S-ALCL). The patient was treated with chemotherapy, followed by allogeneic bone-marrow transplant (BMT). Over the following 6 years, she presented with biopsy-confirmed LyP relapses with complete cutaneous, peripheral-blood and bone-marrow chimerism. This is only the third reported paediatric association of S-ALCL with LyP to our knowledge, and seems to be the first paediatric case of recurrent relapses of LyP after bone-marrow allograft for S-ALCL with total (100%) cutaneous and bone-marrow chimerism. LyP occurring after allogenic BMT does not appear to be donor-derived.

Melanoma gene expression and clinical course.

Evidence for the in vitro lymphocyte response against autologous melanoma has been accumulating over the past 10 years, leading to the identification of numerous melanoma-associated antigens recognised by T cells. These antigens are targets for specific immunotherapy protocols. However, their expression is heterogeneous during tumour progression and may contribute to therapeutic escape mechanisms and disease progression. This study was designed to chart the importance of these escape mechanisms, and to assess the relationship between gene expression and the clinical profile (especially survival data) of patients with melanoma. We studied the expression of certain melanoma genes in tissue biopsies from 202 patients using reverse transcriptase-polymerase chain reaction (RT-PCR). The evaluated genes were Melan-A, tyrosinase, Na-17A, MAGE-1, MAGE-3 and Ny-ESO-1. We then correlated the results to the patients' survival data. 202 samples (cutaneous, nodal and visceral biopsies) were analysed by RT-PCR. No relationship was found between clinical data and gene expression. No relationship was found between survival data and gene expression, when samples of all stages were combined in the analysis. However, interactions between gene expression and disease stage were significant. When stage III samples alone were considered, MAGE-3 expression alone or in association with the expression of the other tumour-specific genes was found to be significantly associated with a higher disease-free survival (respectively, P = 0.0349; 0.007). Our results provided no evidence for a relationship between gene expression and clinical data, or between gene expression and survival data. However, with regard to certain sub-groups, such as stage III samples, tumour gene expression was significantly associated with survival.

Effects of a combined antithrombin III and protein C supplementation in porcine acute endotoxic shock.

Antithrombin III (ATIII) and protein C (PC) are major inhibitors of the coagulation cascade and might regulate the cytokine network. We tested the possibility that a combined supplementation using these two inhibitors might have synergistic effects on sepsis-induced disseminated intravascular coagulation and shock. Hemodynamics, coagulation parameters, tumor necrosis factor (TNF) alpha, and interleukin 6 levels were measured in pigs submitted to a bolus infusion of Escherichia coli endotoxin (lipopolysaccharide). Four groups were studied: control lipopolysaccharide, ATIII (100 IU/kg), PC (50 IU/kg), and ATIII-PC (same doses). The endotoxin infusion resulted in a typical hypokinetic shock with disseminated intravascular coagulation in all animals. Compared with the control group, a significant improvement in mean arterial pressure and systemic vascular resistance was observed in the PC and ATIII-PC groups. The increase in lactate levels was almost completely blunted in the PC group. A significant lesser increase in TNFalpha levels was observed in the ATIII-PC group. No effects were seen on interleukin 6 levels. Coagulation and fibrinolysis parameters were not improved by ATIII and/or PC, except for a lesser decrease in prothrombin time in the ATIII-PC group. We conclude that in this acute endotoxic model, a combined supplementation using PC and ATIII concentrates has favorable effects on hemodynamic parameters and TNFalpha levels, independently from the anticoagulant actions of these inhibitors.

Effects of inter-alpha-inhibitor in experimental endotoxic shock and disseminated intravascular coagulation.

We investigated the effects of human inter-alpha-inhibitor (I alpha I) on hemodynamics, oxygenation, and coagulation parameters in a porcine model of endotoxic shock. Four groups of six animals were studied: (1) control, (2) I alpha I group receiving 30 mg/kg I alpha I over 30 min, (3) LPS group receiving 5 micrograms.kg/min Escherichia coli endotoxin over 30 min, and (4) LPS + I alpha I group receiving 30 min after endotoxin 30 mg/kg/30 min I alpha I. We measured hemodynamic and oxygenation parameters, usual coagulation markers and plasma levels of thrombin-antithrombin complexes, antithrombin III activity, plasminogen activator tissue type, plasminogen activator inhibitor type 1, von Willebrand factor, tumor necrosis factor-alpha, and I alpha I at baseline and at 30, 60, 90, 120, 180, 240, and 300 min. In the I alpha I group, plasma I alpha I levels reached 447 +/- 23 mg/L just after injection and 287 +/- 39 mg/L at 300 min. I alpha I half-life was 7.3 +/- 1.9 h. In the IPS + I alpha I group, I alpha I plasma levels decreased more rapidly, reaching 260 mg/L at 300 min. Compared with the LPS group, administration of I alpha I normalized the mean arterial pressure and cardiac index, improved the LPS-induced pulmonary hypertension, and resulted in the blunted increase in blood lactate and oxygen extraction ratio. A significant decrease in thrombin-antithrombin complexes and plasminogen activator inhibitor type 1 levels were observed. There was no significant difference in plasma tumor necrosis factor-alpha levels. We concluded that in this hypodynamic model of endotoxin shock, I alpha I administration resulted in a marked improvement in the hemodynamic, oxygenation, and coagulation parameters.

Glucocorticoid inhibition of Na-Pi cotransport in renal epithelial cells is mediated by protein kinase C.

The effect and mechanism of action of glucocorticoids (GC) on Na-Pi cotransport were evaluated in opossum kidney cells. Dexamethasone (1-1000 nM) inhibited sodium-dependent Pi uptake in a time- and concentration-dependent manner. Inhibition was maximal after a 6-h incubation with dexamethasone and was prevented by cycloheximide and actinomycin D. The effect was related to a 37% decrease of the Vmax value after incubation with 100 nM dexamethasone. The effect of dexamethasone was mimicked by cortisol and blocked by GC receptor antagonists RU38486 and progesterone. GC affected neither glucose or alanine uptake nor Na/H exchange activity. Inhibition of Pi uptake persisted when Na/H was blocked by amiloride or dimethylamiloride. GC had no effect on basal or parathyroid hormone- and forskolin-stimulated intracellular cAMP content. Dexamethasone and extracellular cAMP, parathyroid hormone, or 3-isobutyl-1-methylxanthine had additive inhibitory effects on Pi uptake. Staurosporine, GF109203X, or calphostin C (three dissimilar inhibitors of protein kinase C (PKC)) and PKC down-regulation blunted the inhibitory effect of glucocorticoids on Pi uptake. GC increased both membrane-bound PKC activity and the membrane/cytosol PKC activity ratio. This is the first report of GC activation of PKC in renal cells, which appears to mediate the steroid inhibitory effect on Pi transport.

[Double and triple neoplasms in endometrial carcinoma]. / Doppel- und Dreifachmalignome beim Endometrium-Karzinom.

From 1968-1992 1503 endometrial carcinomas have been evaluated at Bad Trissl Clinic retrospectively. All double and triple carcinomas have been histologically recorded, doubtful cases have been excluded. Double malignomas that occurred within 6 months are termed simultaneous, all others are termed successive ones. Of 1503 endometrial carcinomas 163 (10.8%) were multiple tumors. Of these 100 (6.6%) occur together with breast cancer and 63 (4.2%) with other primary malignomas. 145 (9.6%) are double, 18 (1.2%) are triple malignomas. 10 precancerous cases (0.7%) have been included in the survey. The average latency period from the first to the second malignoma was 4.5 years. Patients with endometrial carcinoma run higher risks of secondary tumors. One out of 10 develops a double malignoma, one out of 100 a triple malignoma. The combination of endometrial and breast cancer occurs in 60% of cases, the combination of genital and breast cancer in nearly 80% of cases. After-care of endometrial carcinoma must also include early detection of potential double and triple malignomas.

Modulation of Na-H exchange activity by angiotensin II in opossum kidney cells.

Angiotensin II (ANG II) was shown to modulate transport in the renal proximal tubule through both inhibition of adenylate cyclase and protein kinase C (PKC) activation. We evaluated the effects of ANG II on adenosine 3',5'-cyclic monophosphate (cAMP) content and Na-H exchange activity (amiloride-sensitive Na influx) in two strains of opossum kidney (OK) cells originating from different sources, OK-VD and OK-RR cells. In OK-VD cells, ANG II inhibited basal and parathyroid hormone (PTH)-induced cAMP generation in a pertussis toxin-sensitive manner and reversed PTH inhibition of Na-H exchange. These effects of ANG II were prevented by PD 123319, a selective nonpeptide antagonist of AT2 receptors. In contrast, DuP 753, which antagonizes selectively AT1 receptors, had no effect. In OK-RR cells, ANG II had no effect on cAMP content and decreased Na-H exchange activity. The effect of ANG II persisted in the presence of PTH but was abolished by PKC downregulation and by DuP 753, but not by PD 123319. In conclusion, two types of ANG II receptors, coupled to distinct signaling pathways, were expressed independently in OK cells originating from two different sources and mediated opposite effects of ANG II on Na-H exchange activity. Those models provide a powerful tool for studying the intracellular steps involved in the tubular effects of ANG II and to evaluate the effect of pharmacological inhibitors of ANG II binding to its receptors.

[Multiple tumors in endometrial cancer]. / Mehrfachtumoren beim Endometriumkarzinom.

Out of 1220 (100%) cases of endometrial carcinomas, registered at the Klinik Bad Trissl during a period of 20 years (1968-1988), over 127 cases (10.4%) of double and triple malignomas were found. 86 cases (7.0%) are correlated with a second primary breast cancer, 41 (3.4%) with other primary malignomas. 14 cases (1.1%) show triple malignomas. 8 precancerous cases (0.7%) were included in the survey. Contrary to medical literature the survey reveals a different distribution of neoplasms among the affected organs. Four fifths of the tumour combinations were located in the female genital tract including the breast. Therefore the early detection of potential secondary malignomas should be included in the aftercare of endometrial cancer.

[The value of skeletal scintigraphy in the aftercare of breast carcinoma. A prospective study of 750 cases]. / Stellenwert der Skelettszintigraphie in der Nachsorge des Mammakarzinoms. Eine prospektive Studie über 750 Fälle.

In 1987/88 a prospective study was undertaken of 750 patients with postoperative carcinoma of the breast but no evidence as yet of skeletal metastases. A thorough history regarding pain was taken with pre-set questions and an exact clinical examination conducted to reveal any skeletal pain. Subsequently whole-body skeletal scanning was performed, plus additional X-ray films, determination of tumour markers CA-15-3 and CEA, and further tests as indicated. Clinical and imaging results agreed in 649 patients. In 70 patients the clinical suspicion or questionable finding of metastases was not confirmed by radiology or a scan. Bone metastases would have been missed in only 14 patients (1.9%) without a skeletal scan. Eleven of these 14 patients were in high-risk groups (negative hormone receptor status; axillary lymph node metastases). Skeletal metastases were undiscovered in only three of the 750 patients (0.4%). It is thus sufficient to limit skeletal scans to high-risk groups, as long as a careful history of pain is taken and a thorough clinical examination conducted.