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Presents guidelines of Standards, Options and Recommendations (SORs) for the use of serum tumor markers in breast cancer. Characteristics of breast cancer tumor markers; Role of breast cancer tumor markers in the management of patient with cancer; Methodology for the development of the SORs for serum tumor markers in breast cancer.

Objective: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT., Methods: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h., Results: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT., Conclusion: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC., (© 2015 John Wiley & Sons Ltd.)

Objective: To assess the vitamin D status of children aged 6-10years in the French general population for whom no guidelines have yet been defined due to insufficient data., Method: The study was conducted during two winters with very different sunshine levels: 5 March to 17 April 2012 and 8 January to 16 April 2013 in 20 then 22 centers. Three hundred children (60 children for each year of age) attending an ambulatory care unit or outpatient department for a reason unrelated to vitamin D status were included at the end of winter in 20 hospital centers (ten centers in the northern half of France above latitude 46-47°N/Lille: 50°N and ten centers in the southern half of France below latitude 46-47°N/Marseille: 43°N). Centralized 25 hydroxyvitamin D (25(OH)D), alkaline phosphatase (ALP), and parathormone (PTH) assays were performed on leftover blood samples. The currently accepted normal range for 25(OH)D was used to define the following categories: ≤25nmol/L: severe vitamin D deficiency, 25nmol/L100nmol/L: high vitamin D status. A standardized questionnaire was used to collect the child's characteristics, use of a vitamin D supplement, and milk and dairy product intake. The cumulative number of hours of sunshine over the 90days prior to inclusion in each center was obtained from the Météo-France weather bureau., Results: 25(OH)D assays were performed in 326 children; more than 95% of children received milk and dairy products and 38% had received a vitamin D supplement since starting the school year: 3.1% of children in the overall population presented severe vitamin D deficiency, 34.4% presented vitamin D deficiency, 53.1% had a sufficient vitamin D status, and 9.5% had a 25(OH)D concentration >100nmol/L with no impact on serum calcium and urinary calcium. Children living in the north of France generally had lower 25(OH)D levels than children living in the south of France. In the non-supplemented population (n=188), 5.3% of children presented severe vitamin D deficiency, 45.2% presented vitamin D deficiency and 48.4% had sufficient 25(OH)D levels. The percentage of children with severe vitamin D deficiency or vitamin D deficiency was twofold higher during the winter with poor sunshine compared to the sunnier winter with a less marked north/south difference. No case of severe vitamin D deficiency was observed in the supplemented population (n=119); 10-15% of children presented vitamin D deficiency and 22.7% had a 25(OH)D concentration >100nmol/L, while remaining within the acceptable range. Two cases of hypervitaminosis without hypercalcemia were identified: one after an unknown loading dose with a calcium/creatinine ratio in the normal range (0.8); for the second one, no additional information could be obtained. Vitamin D supplementation considerably reduced the north/south difference and the Winter1/Winter2 difference. A child not receiving a vitamin D supplement had a ninefold higher risk of vitamin D deficiency at the end of winter than a child receiving a vitamin D supplement (OR=8.8; 95%CI, 4.6-16.8)., Conclusion: At least one-third of children aged 6-10years presented deficient 25(OH)D levels. None of the children receiving a vitamin D supplement presented severe vitamin D deficiency, only a small number of children presented vitamin D deficiency (n=16 (13.4%)), and no signs of overload were observed, while one half of non-supplemented children (n=95 (50.5%)) presented at least vitamin D deficiency at the end of winter. These results support the need for vitamin D supplementation during winter in children aged 6-10years., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis., Methods: Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels., Key Results: Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal., Conclusions & Inferences: Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis., (© 2013 John Wiley & Sons Ltd.)

Aims: The aim of the study was to assess compliance with the current recommendations of prophylactic prescription of vitamin D via a multicentric cross-sectional epidemiological survey of 3240 children under 6 years of age., Method: Parent questionnaires and data from the health records of children presenting to the emergency departments of 25 teaching hospitals and hospital centers provided information on the children's characteristics, their prescriptions, and other vitamin D intake. Based on the currently applicable recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with pigmented skin and/or premature and/or hypotrophic children - are considered adequate., Results: In 1606 infants, 9.8% of the prescriptions were below and 23.7% were above the recommendations; in 1256 children between 18 months and 5 years of age, 53.4% of the prescriptions were below and 5.1% were above the recommendations. Children at risk, those from the southern half of France, and those between 18 months and 5 years of age were more likely to receive a prescription below the recommendations; their risk of receiving a prescription above the recommended guidelines was smaller. Of the children aged between 61 and 71 months, 85% had not received any prescription at all during the previous 12 months. These results were compared with the laboratory data collected from a subsample of children. There was a significant correlation between the adequacy of the prescription and the biological vitamin D status both for 25-hydroxyvitamin D (25-OH-D) serological concentrations and for calciuria., Conclusions: Only 66.6% of the prescriptions in children between 0 and 18 months of age and 41.5% in children between 19 months and 5 years of age comply with the recommendations; 53.4% of the prescriptions in the latter age group are below the current recommendations., (Copyright © 2012. Published by Elsevier SAS.)

Aim: To investigate in a prospective study the prognostic value of serum HER2 extracellular domain (ECD) level in patients with primary breast cancer overexpressing HER2 treated with adjuvant chemotherapy and trastuzumab., Patients and Methods: All the patients treated for primary breast cancer with chemotherapy and adjuvant trastuzumab from April 1, 2005 to December 31, 2006 at the Centre de Lutte Contre le Cancer de Haute Normandie were enrolled in this prospective study. HER2 ECD was measured in frozen serum by a commercial kit with a cut-off value of 15 ng/ml., Results: Sixty-five patients were enrolled. Seven patients (11%) had an elevated serum HER2 ECD level (mean=25.1 ng/ml, range 15.1-38.9 ng/ml). During follow-up, 13 patients (20%) developed metastases and seven patients (11%) died. Death was related to breast cancer metastases in six patients (9%). Out of the seven patient with elevated serum HER2 ECD level, five (71%) developed metastases and three (43%) died of metastases during follow-up. Multivariate analysis showed that elevated serum HER2 ECD level was the unique factor for both disease-free survival (p<0.0006) and overall survival (p=0.008) in this series., Conclusion: Elevated serum HER2 ECD level is a strong prognostic factor in primary breast cancer overexpressing HER2 treated with adjuvant therapy of trastuzumab. In addition, our results suggest that it could predict failure of adjuvant therapy of trastuzumab.

Introduction: The analytical performance and the abnormality messages on differential (flags) of the new analyzer Beckman Coulter DxH 800 were compared with those of the LH 755., Methods: First, we evaluated the accuracy of the results of the DxH 800, in comparison with the LH 755, in 125 samples without alarm using unflagged sample results on both analyzers. Second, flagged samples on the LH 755 but not flagged by the DxH 800 were evaluated by flow cytometry for accuracy of the DxH 800 results. Finally, we evaluated the sensitivity and specificity of abnormality messages on differential given by the analyzers, in comparison with manual blood smears., Results: The correlation coefficients (R) for complete blood count parameters and differential demonstrated that the DxH 800 results were similar to that of LH 755. Excellent correlation coefficients between DxH 800 and flow cytometry results were found for white blood cell count (R = 0.985, n = 31), platelet count (R = 0.976, n = 51) and nucleated red blood cells (R = 0.966, n = 37). The overall performance showed an increased sensitivity (0.892) and specificity (0.864) of the flags on DxH 800 when compared to the LH 755 (0.846 and 0.733, respectively)., Conclusion: The DxH 800 provides reliable results and increases laboratory efficiency by reducing working time and costs associated with the optical validation of the results., (© 2010 Blackwell Publishing Ltd.)

Adolescence, a period of growth and acquisition of bone mass, requires adequate calcium and vitamin D intake. This study was designed to assess the impact of a single loading dose of 200,000 IU of vitamin D(3) on the winter vitamin D status of healthy adolescents. Vitamin D status was assessed by 25-OH-D levels before, 3 weeks, and 3 months after this single dose, and safety was assessed by serum calcium and PTH and urinary calcium excretion in random samples from 27, 23, and 17 healthy adolescents derived from the same institution. The 25-OH-D peak value 2 weeks after the vitamin D supplement of 71-129 nmol/l (mean, 96 nmol/l), and a residual level at 3 months of 29-83 nmol/l (mean, 57 nmol/l) serum calcium and urinary calcium excretion expressed by the calcium/creatinine ratio were normal and stable at 2 weeks and 3 months, remaining less than 0.5 for the calcium/creatinine ratio. This simple measure, ensuring good compliance during adolescence, ensures optimal winter vitamin D status with no signs of overload., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Background: Thyrotropin (TSH) stimulates thyrocyte metabolism, glucose transport, and glycolysis. The interest in using recombinant human TSH (rhTSH) stimulation of fluoro-2-deoxy-D-glucose (FDG) with positron emission tomography (PET) has been shown, but mainly for patients with high serum thyroglobulin (Tg) concentration. We evaluated the use of rhTSH-stimulated PET-FDG in patients with low serum Tg concentration., Methods: Sixty-one PET/computed tomography (CT)-FDG (Biograph Sensation 16; Siemens Medical Solutions, Knoxville, TN) were performed in 44 patients (28 women and 16 men; 51 +/- 16 years) with positive Tg levels, negative or no contributive iodine-131 whole-body scintigraphy results, and no contributive morphological imaging results (ultrasound, magnetic resonance imaging, and CT). Thirty-eight patients had papillary carcinoma and six had follicular thyroid carcinoma. All patients had previously undergone total thyroidectomy and postoperative iodine ablation of thyroid bed remnant tissue. The rhTSH-stimulated PET/CT-FDG (5 MBq/kg) was performed after two 0.9 mg intramuscular doses of rhTSH (Thyrogen; Genzyme) which were administered 48 and 24 hours before imaging, while patients continued levothyroxine (LT(4)). Blood sampling was performed immediately before FDG injection for measurement of serum TSH and Tg concentrations (TSH(1) and Tg(1)) and after 48 hours (TSH(2) and Tg(2)). PET/CT-FDG findings were compared with the Tg: (i) at the initial iodine treatment during T(4) withdrawal (Tg(ini)), (ii) under T(4) (Tg(T4)) within 3 months before the PET/CT-FDG, (iii) with Tg(1), and (iv) with Tg(2). PET/CT-FDG findings were correlated with the findings of histology, iodine-131 whole-body scintigraphy, morphological imaging, or clinical follow-up., Results: The mean Tg(ini) was 785 +/- 2707 microg/L for a TSH of 73 +/- 64 mU/L. The mean Tg(T4) was 7 +/- 15 microg/L (T(4) = 195 +/- 59 microg/day; mean TSH of 0.24 +/- 0.57 mU/L). Among the 44 patients, PET/CT-FDG findings were positive in 20 and negative in 24. Among the 61 PET/CT-FDG, 25 PET/CT-FDG were positive (41%). Among the 25 positive PET, the Tg(T4) values were less than 10 microg/L for 19, including 9 true-positive patients (20% of the 44 patients). There was no difference of PET/CT-FDG results (positive vs. negative) as related to the serum Tg concentrations (p = 0.99 for Tg(ini), p = 0.95 for Tg(T4), p = 0.07 for Tg(1), and p = 0.42 for Tg(2)). No relation was observed with PET/CT-FDG results and initial tumor size (p = 0.52) or node metastasis (p = 0.14)., Conclusion: In the diagnosis of recurrent disease in patients with differentiated thyroid carcinoma and low Tg level, the sensitivity of rhTSH-stimulated PET/CT-FDG seems to be low and no correlation was observed between PET/CT-FDG findings and Tg level. However, positive PET-FDG results have been found in 9/44 (20%) patients with serum Tg levels lower than 10 microg/L. Therefore, this series shows that a cutoff value of 10 microg/L for the Tg under T(4) is probably not the best criteria to select patient candidates for PET/CT-FDG examination to detect the recurrence of differentiated thyroid carcinoma.

This clinical report illustrates the usefulness of routine CA 15.3 assay during the follow-up of patients treated for invasive breast cancer. This patient presented an isolated elevation of CA 15.3 eighteen months after initial treatment of inflammatory breast cancer. The scientific committee for breast cancer decided to modify the hormonotherapy, even without clinical or radiological event (tomodensitometry, echography, scintigraphy). The prompt CA 15.3 normalization persisted for more than seven years. When CA 15.3 levels increased again, a positron emission tomodensitometry was performed and revealed pulmonary nodes. The sole modification of hormone treatment, based upon isolated increase of CA 15.3, led to seven years of clinical and biological stability for our patient with probable pulmonary metastases.

Background: Quality control results for serum MUC-1/CA 15-3 assays have always shown large discrepancies., Methods: This multicentre study of 15 methods (labelled M1-M15) measured coded sera from 35 patients with breast cancer without recurrence (group 1), 46 patients at 1st metastasis (group 2), and 39 patients with advanced metastases (group 3). Results were compared using parametric statistics, ANOVA, principal component analysis, and receiver operating characteristic (ROC) curves., Results: Mean MUC-1/CA 15-3 concentrations varied widely (75.1-303.0 U/mL, 24.8%) among methods. The false positive (FP) rate for group 1 was 8/521 (1.5%); for group 2 and group 3 false negative (FN) results were 21/680 (3.1%) and 11/583 (1.9%), respectively. Using the ROC cut-offs, we found no FPs for group 1 and no FNs for group 3. However, group 2 showed 16 FNs. All p-values for Pearson's correlation were <0.0001 between methods, except for M11. When comparing methods using different antibodies, discordance rates reached a maximum of 15.2%. Principal component analysis revealed a grouping of methods using: CanAg monoclonal antibodies (mAbs) (M2, M7 and M12); Centocor/Fujirebio mAbs (M3-M6, M8-M10, M14-M15) and Biomira mAbs (M1 and M13); and Centocor/Fujirebio mAbs (M11)., Conclusions: Results were more consistent among methods using the same antibody type. Principal component analysis showed that antibody type was the strongest determinant of immunoassay results.

Background: CA 125 assays enable treatment-response monitoring in ovarian cancer., Methods: A multicentric study of CA 125 kinetics under paclitaxel/platinum-based chemotherapy was performed in 130 stage IIc-IV patients. CA 125 half-life and nadir concentration were compared to patient outcome. Some patients (n=38, 29.2%) presented a CA 125 bi-exponential decrease and its clinical implication was studied. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox model)., Results: During a median follow-up time of 29 months (range 5-106 months), 111 patients (85%) relapsed and 94 (72%) died from ovarian cancer. Patients were split into 4 groups according to their pattern of CA 125 decrease: non-assessable half-life because of a low pre-chemotherapy CA 125 level (n=38), half-life < or = 14 days and mono-exponential CA 125 decay (n=18), half-life < or = 14 days and bi-exponential CA 125 decay (n=21), and half-life > 14 days (n=53). In Cox models, nadir concentration, residual tumour volume and number of chemotherapy courses were found to be independent prognostic factors for DFS and OS. The group classification was found to be an independent prognostic factor only for DFS. However, when nadir was not introduced in the models, the CA 125 kinetics groups were the most important prognostic factor for OS., Conclusion: Characteristics of CA 125 kinetics during first line paclitaxel/platinum chemotherapy have a strong and independent prognostic value. A CA 125 bi-exponential decrease is an indicator of bad prognosis.

Acute bronchiolitis is the main cause of emergency visits and hospitalizations in infants. Recent data suggest that neutrophil- and eosinophil-mediated inflammations were part of bronchiolitis pathophysiology. Apart from the defined risk factors, few was known on the underlying pathophysiology, which might point out the differences observed in the severity of the disease. The aim of this study was to assess whether the clinical severity of acute epidemic bronchiolitis in young infants might be related to a specific underlying inflammatory process. Total and differential cell counts, IL-8, eotaxin, eosinophil cationic protein (ECP) and albumin levels were assessed at the time of admission in bronchial secretions from 37 infants (median age 17 wk) with acute bronchiolitis. Outcome severity variables were: hypoxemia, Silverman score, tachypnea, feeding alteration, and duration of hospitalization. Neutrophils predominated, and eosinophils were present in 54% of the infants. IL-8 levels strongly correlated with ECP and albumin levels. Albumin levels were correlated with ECP and eotaxin levels. IL-8 levels were higher in infants with hypoxemia and inversely related with SaO(2) levels. IL-8 and albumin levels significantly rose with respiratory rate, and Silverman score. IL-8, albumin and ECP levels were significantly higher in infants hospitalized >/=7 days. Furthermore, IL-8 levels were correlated with the duration of hospitalization. Neither cell counts nor eotaxin levels were related to the severity criteria studied. This study suggests that IL-8-associated airway inflammation significantly contributed to the severity of acute epidemic bronchiolitis.

Objective: The diagnosis of primary hyperparathyroidism (PHP) can be difficult in patients with normal plasma calcium or parathyroid hormone (PTH) levels. We perfected a standardized short-time i.v. calcium loading test in healthy controls (HC) and compared the results with those of patients with PHP., Methods: Sixteen HC received 0.33 mmol/kg calcium gluconate intravenously for 3 h. Plasma calcium and serum PTH levels (assayed with immunoluminescent sandwich methods) were measured before, at the end of the infusion and 3 h later. Results were compared with those of 16 PHP patients., Results: In HC, basal total plasma calcium (mean +/- s.e.m.) was 2.33 +/- 0.02 mmol/l. At the end of calcium loading, calcemia reached 3.21 +/- 0.05 mmol/l and decreased to 2.94 +/- 0.08 mmol/l 3 h later. In PHP patients, basal plasma calcium was 2.54 +/- 0.03 mmol/l and reached similar values as in HC during the testing. Basal serum PTH levels were 32.5 +/- 3.3 ng/l in HC and 86.9 +/- 6.3 ng/l in PHP. At the end of calcium loading, they dropped to 8.8 +/- 0.6 ng/l (HC) and to 31.4 +/- 4.2 ng/l (PHP). Three hours later, they were 11.6 +/- 0.8 and 39.8 +/- 4.0 ng/l respectively. There was a cut-off in serum PTH values between the two groups at the end of calcium loading and 3 h later., Conclusion: The standardized short-time PTH suppression test appears reliable to differentiate healthy subjects from PHP whose serum PTH levels remain >14 and >23 ng/ml respectively at the end of loading and 3 h later. This well-tolerated and easily performed test could be used for the diagnosis of PHP in patients suspected for the disease despite the normality of some basal biological markers.

Background: CA 125 assays enable treatment response monitoring in ovarian cancer., Patients and Methods: This multicentric study was carried out to assess the prognostic value of the CA 125 change after the first and the second courses of induction chemotherapy (CT). Of the 494 stage IIc-IV patients, 194 had a surgical second look, 397 (80.4%) relapsed and 382 (77.3%) died from cancer. Median (range) follow-up time was 34 months (3-215 months)., Results: In Cox models, CA 125 change after the first course (P < 0.0001), residual tumour (P = 0.003), CA 125 before the second course (P = 0.025) and patients' age (P = 0.048) were independent prognostic factors for overall survival (OS). A normal CA 125 before each of the two first CT courses or a CA 125 decrease >50% after the first course with a normal CA 125 before the second course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (P < 0.0001)., Conclusion: Among well-established prognostic factors in ovarian cancers, the CA 125 change after first course of CT was independent prognostic factors for both achievement of pathological complete response and OS.

Background: CA 125 assays enable treatment-response monitoring in ovarian cancer., Patients and Methods: A multicentric study of CA 125 kinetics under induction chemotherapy was performed in 631 patients. CA 125 half-life was calculated by mono-compartmental logarithmic regression. Nadir CA 125 concentration and time to nadir were also studied. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) models., Results: For 553 stage IIC-IV patients, 459 (83.0%) relapsed and 444 (80.3%) died from cancer. Median (range) follow up time was 32 months (2-214 months). Median (range) for CA 125 kinetics were: 263 kU/l (5-52000 kU/l) before 1st course, 15.8 days (4.5-417.9 days) for CA 125 half-life, 16 kU/l (3-2610 kU/l) for nadir and 85 days (0-361 days) for time to nadir. Pre-chemotherapy CA 125, its half-life, nadir concentration and time to nadir all had a univariate prognostic value for DFS and OS (P<0.0001). In Cox models, CA 125 half-life, residual tumour (P<0.0001 for both), nadir concentration (P=0.0002) and stage (P=0.0118) were the most powerful prognostic factors for DFS. For OS, the significant variables were similar, with age ranking last (P=0.0319)., Conclusion: Among well-established prognostic factors in ovarian cancers, CA 125 half-life and nadir concentration bear a strong and independent prognostic value.

Few data are available regarding calcium and vitamin D intake in toddlers, despite a remaining high growth velocity. Therefore, a study was carried out in the Rouen geographical area where the sunshine is limited. It appears that a great majority of the children studied (9/10) received plain milk, and subsequently only small quantities of vitamin D or calcium enriched milk. Nevertheless, 12% of primarily 4 to 6 year-old children do not received daily minimum requirements, and 6% of them had vitamin D insufficiency, which was demonstrated by 25OHD plasma concentrations. These concentrations declined from 18 months to 6 years old were related to discontinuation in vitamin D supplements. A great variability was observed in vitamin D supplementation as no official recommendations were followed. Modalities of this supplementation should be reconsidered.

The aim of our study was to evaluate five different free/total PSA (f/t PSA) kits for the diagnosis of early stage prostate cancer. We compared the PSA density and the f/t PSA ratio to differentiate between benign prostatic hyperplasia (BPH) and prostate cancer. This prospective study included a total of 120 patients with suspected prostate cancer (PSA between 4 and 15 ng/ml) observed over a period of 30 months. All patients had a blood test as well as a prostate biopsy prior to inclusion. Serum immunoassay total-PSA (t PSA) and free-PSA (f PSA) were carried out using five different assay kits: IMX Abbott (A), Kryptor Brahms (B), Immulite DPC (D), IRMA Immunotech (I) and IRMA DiaSorin (S). The results were compared to determine sensitivity, specificity, threshold values, and to differentiate between BPH and cancer. No difference was found between assay reproducibility and variation in the assays, however, only a slight variation was observed in the mean t PSA values, whereas a significant difference was found with f/t PSA. Receiver operating curves were generated for t-PSA and f/t PSA. The area under the curves did not show any significant differences for either t PSA or f/t PSA. A low comparative variability between the five kits tested for tPSA was observed, which suggest that the f/t PSA ratio has no current usefulness in the initial diagnosis of prostate cancer, particularly in patients with larger prostates. Furthermore, no prognostic value was found for surgically positive margins in radical prostatectomy.

Context: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the French Federation of Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients., Objective: To update clinical practice guidelines for first line medical treatment of patients with ovarian neoplasms in collaboration with the French Society for Gynaecologica Oncology., Methods: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts. The CPGs are defined following the definitions of the Standards, Options and Recommendations project. Once the guideline has been developed, the document is submitted for review by independent reviewers., Results: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. After surgery, most patients with ovarian neoplasms need adjuvant medical treatment. These guidelines concern the initial medical treatment (chemotherapy, hormone treatment and immunotherapy) and potential consolidation treatment. To complete the indications, two alternative treatment strategies are taken into account: no treatment and radiotherapy. This updated version concerns the indications and the modalities of chemotherapy. The main modifications are: 1) first-line chemotherapy for ovarian neoplasm can be taxane-platinum or carboplatine alone; 2) poly-chemotherapy is no longer a standard; 3) for early stages, except for stage IA grade I non-clear-cell tumours, adjuvant chemotherapy should be preferred to no treatment; 4) chemotherapy is standard for all stage III tumours, irrespective of the surgical result; 5) for stage IA G2-3 to IIA tumours, complete surgical staging and determination of the histological grade are standards., (Copyright John Libbey Eurotext 2003.)

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French cancer centers and specialists from French public university and general hospitals and private clinics. Its main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop, according to the definitions of the Standards, Options and Recommendations, clinical practice guidelines for the management of invasive cervical cancer patients. Methods : Data were identified by searching Medline and the personal reference lists of members of the expert groups, then submitted for review to independent reviewers., Results: This is a synthesis of the Standards, Options and Recommendations elaborated by a working group of experts. Pretherapeutic assessment, classification, diagnosis, therapeutic modalities (surgery, radiotherapy, radiochemotherapy, chemotherapy), therapeutic strategies by disease stage and follow-up are covered. Algorithms for the management of patients are also included.

Bisphosphonates, such as pamidronate, are a new class of drugs, initially described for treatment of neoplasic hypercalcemia. Currently, they also may be used in the treatment of bone metastases from solid tumor, even without hypercalcemia. Hypocalcemia is a potential adverse effect of these drugs, which is considered infrequent and rarely symptomatic. We describe three cases of severe hypocalcemia following one injection of pamidronate. The three patients had bone metastases from solid tumors (breast in two cases, prostate in one), at least partially osteoblastic, and none had hypercalcemia. The induced hypocalcemia was rapid in onset, severe, and durable. The mechanism seems to be multiple and may include both the expected reduction of osteolysis and also a rapid and direct action on parathyroid glands followed by resistance to parathormone. Some elements could amplify the phenomenon, such as latent hypoparathyroidism after surgery, cervical radiotherapy, hypomagnesemia, or low 25 hydroxy vitamin D (25OH D). For patients who have such risk factors, it may be useful to check calcium several days after the first injection.

Mathematical analysis of CA125 kinetics during first line chemotherapy allows calculation of various biologic parameters which are powerful indicators of the therapeutic efficiency. The purpose of this study is to present an original method of interpretation of CA125 kinetics based on both CA125 profile and its half-life value. The first part of this study reviews the practical modalities of CA125 kinetics analysis, the methods of calculation of the biologic parameters as well as the guidelines of interpretation. The second part of this work is dedicated to the presentation of CA125 profile characteristics in responders to chemotherapy, partially or totally nonresponders to chemotherapy, tumoral growth under treatment and tumor lysis syndrome.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the French National Federation of Comprehensive Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public University or General Hospitals, and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome of cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in colorectal cancer and their potential role in the management of patients with this malignancy., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 117 independent reviewers, and to the medical committees of the 20 French Cancer Centers., Results: The main recommendations for the tumor markers in colorectal cancer are: 1) The carcinoembryonic antigen (CEA) is the reference serum marker (standard). 2) All the analyses for a given patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 3) CEA or CA 19-9 should not be used for screening or diagnosis (standard, level of evidence B2). 4) High initial serum concentration of CEA is of bad predictive value (standard, level of evidence C). CEA is an independent prognostic factor of survival in colorectal cancers with lymph node metastases (standard, level of evidence B2). 5) CEA is the most sensitive biological parameter for the screening of hepatic metastases (standard, level of evidence B2). 6) CEA serum concentration before palliative chemotherapy is an independent prognostic factor of survival (standard, level of evidence B2). The combination of CEA assay with imagery techniques and clinical examination can help monitor the response to palliative chemotherapy (standard), in particular in non measurable disease (standard, expert agreement). 7) In 65% of the cases, CEA is the first indicator of relapse (standard, level of evidence B2). CEA is the choice marker for monitoring patients with colorectal cancer (standard, level of evidence B2). 8) A sustained biological follow-up including CEA assay can be used to predict the operability of recurring tumors (standard, level of evidence B2). Nevertheless, no survival advantage has been shown (standard).

The determination of tumor markers may have consequences for the patients' treatment, which requires special attention to the analysis and to the expression of the results. In addition to the factors usually dealt with in the pre-analytical phase (identification, quality and storage of the sample) and in the analytical phase (interference, endogenous antibodies, hook effect), we must consider factors such as normal values (which depend heavily on the used techniques), threshold values defining other characteristics (sensitivity, specificity, positive and negative predictive value) and kinetics. Knowledge of the limitations of the tumor marker analysis, in particular tumor markers for non-cancerous diseases leading to possible increases (false positives), is also indispensable. All of this led to the definition of guidelines for good practice, including the design of quality control, rules for requesting, validation and interpretation of results, and the setting up of a serum library.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in thyroid cancer and the potential role of these markers in the management of patients with this malignancy., Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 55 independent reviewers, and to the medical committees of the 20 French Cancer Centers., Results: The main recommendations are: 1) Thyroglobulin is a serum tumor marker for the monitoring of operated thyroid differentiated neoplasms (standard). 2) It is essential to know if the patient is under TSH stimulation or under thyroid suppression therapy to interpret thyroglobulin results (standard). 3) Thyroglobulin assay must be performed regularly during the monitoring of differentiated thyroid neoplasms (standard, level of evidence B2), should be coupled with the measurement of anti-thyroglobulin antibodies concentration using a sensitive method (standard, level of evidence B2). 4) Thyroglobulin assay should not be performed to detect or diagnose differentiated thyroid neoplasms (standard, level of evidence B2). 5) The methods used to assay thyroglobulin must have a limit of detection lower than 3 mug.l- 1 (standard, expert agreement). 6) Calcitonin is a marker for medullary thyroid cancer (standard). 7) Its assay, associated with RET gene study if indicated, enables medullary thyroid cancer to be diagnosed. 8) The pentagastrin test is essential to diagnose familial forms of medullary thyroid cancer. 9) All analyses for each patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 10) Calcitonin and carcinoembryonic-antigen are serum markers for the monitoring of medullary thyroid cancer and allow the detection of recurrent disease (standard).

Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium., Methods: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

It has been shown previously that airway eosinophils characterize childhood asthma and neutrophils contribute to the pathophysiology of both infantile wheezing and asthma. Therefore, eosinophil cationic protein (ECP) and interleukin-8 (IL-8) levels in bronchoalveolar lavage fluid (BALF) from asthmatics (n = 16) and infantile wheezers (n = 30) were analyzed as markers of eosinophil- and neutrophil-mediated inflammation. To aid the interpretation, a control group of children (n = 10) with no lower airway pathology were included. Disease severity was assessed by using a symptom score. Surprisingly, no significant difference was found in IL-8 or ECP levels among asthma, infantile wheeze, and control groups. Asthma was characterized by: a correlation between ECP levels and eosinophil counts (r = 0.618, p = 0.014); a correlation between neutrophil number and IL-8 levels (r = 0.747, p = 0.002); and increasing IL-8 levels with symptom score (p = 0.03). In infantile wheezers, IL-8 levels were poorly related to neutrophil number but were significantly increased when neutrophils were > 10%. Although detectable levels were found in all but one symptomatic infant, IL-8 concentrations did not reflect the symptom score in infantile wheeze. ECP was unexpectedly correlated to neutrophil percentages (Rho = 0.832, p = 0.001), and a threshold of ECP>20 ng/ml was associated with persistent symptoms in these infantile wheezers. Hence, in accordance with BALF cellularity, activation of eosinophils was suggested by raised levels of ECP in childhood asthma, but not in infantile wheeze. Neutrophil-mediated inflammation appeared to better reflect the severity of asthma than that of infantile wheeze. Although its meaning remains to be elucidated, ECP was suggested to be a helpful indicator of persistent infantile wheeze. However, its utility as a marker predicting ongoing asthma remains to be established.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the surgical management of carcinoma of the endometrium., Methods: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres., Results: The main recommendations for the surgical management of carcinoma of the endometrium are: 1) where-ever possible, surgery is the primary treatment of both localised and advanced disease; 2) surgery is performed according to the stage of the cancer and the status of the patient; 3) surgery for stages I and II disease entails total abdominal hysterectomy and bilateral salpingo-oophorectomy. A modified radical hysterectomy is undertaken in cases of macroscopic cervical involvement. An omenectomy is recommended for serous papillary types. Pelvic lymphadenectomy for the purposes of precise staging is undertaken if the patient is of good performance status and without bad pronostic factors. Para-aortic lymphadenectomy can be undertaken to determine involvement of para-aortic nodes; 4) surgery for stages III and IV: radical surgery must be undertaken if at all possible with additional treatment as indicated. In the case of advanced disease, debulking surgery is indicated.

Unlabelled: Suprapubic and transvaginal pelvic ultrasound exploration is indicated for suspected ovarian tumor (standard). Diagnosis and search for extension require surgery and pathology examination. Systematic preoperative computed tomography is not recommended (standard). Surgery for cancer of the ovary is a specialized procedure requiring skill in cancer, gynecology, visceral surgery and laparoscopic surgery. If the patient is referred to a specialized center after a primary procedure considered to be inadequate, a new procedure is recommended for staging. Residual tumor volume after the primary procedure has prognostic value. Systematic second look procedures are not recommended for routine practice (standard). For patients with grade IA G1 tumors, there is no indication for complementary treatment (standard). For patients with grade IA G2-3 or clear cell tumors, IB, IC, IIA, there is no standard., Options: no complementary treatment, complementary chemotherapy using platinum, complementary external abdominopelvic radiotherapy. A complementary treatment is recommended for grades IC and IIA. Complementary treatment for grades IIB (no residual tissue), IIC (with residual tissue), III (no residual tissue), is based on: complementary chemotherapy with platinium, complementary external abdominopelvic radiotherapy (options). Complementary treatment for advanced forms (IIB (with residual tissue), IIC (with residual tissue), III (with residual tissue) and IV) is based on polychemotherapy with platinium (standard)., Options: platinium combined with paclitaxel (intravenous), platinium combined with cyclophosphamide and/or doxorubicin (intravenous) or intraperitoneal cisplatin combined with cyclophosphamide (intravenous). The chemotherapy work-up includes physical examination, assay of serum markers (particularly CA125) and abdominopelvic computed tomography (proof level B) (standard). Physical examination is recommended for monitoring patients in complete remission with no sign of suspected recurrence (standard). This document was reviewed in April 1977. The working group again validated the Standards, OPTIONS and Recommendations, without modifications in June 1999.