Search

Laboratory medicine plays a crucial role in patient care, contributing to approximately 70 % of clinical decisions. In collaboration with clinicians, laboratory medicine specialists perform analyses that are useful for diagnosis, screening and prevention. Laboratories are known for their efficiency, which is reached through a rigorous quality system. However, errors can occur, especially given the complexity of the total testing process. These errors may lead to severe consequences, such as incorrect diagnoses or delays in treatment. Errors can occur at every stage of the total testing process, those related to the pre-analytical phase being the most prevalent. To reduce medical errors related to laboratory processes, it is essential to provide training for medical and paramedical staff, optimize production automation, and leverage technological advancements. These considerations have led to the creation of a French Working Group on Sources of Errors in Laboratory Medicine, under the aegis of the French lean society of clinical chemistry and laboratory medicine (Société Française de Biologie Clinique - SFBC). The objectives of this working group are to produce an educational handbook on sources of errors in laboratory medicine, provide training for clinical chemists, and conducting applied research projects to better understand the mechanisms behind specific errors. Ultimately, the aim is to minimize errors and enhance the quality of laboratory tests.

Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care., Methods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland. Eligible patients were male, aged 18 years or older, with histologically confirmed or cytologically confirmed de novo metastatic prostate adenocarcinoma, and an Eastern Cooperative Oncology Group performance status of 0-1 (or 2 due to bone pain). Participants were randomly assigned (1:1:1:1) to standard of care (androgen deprivation therapy alone or with intravenous docetaxel 75 mg/m 2 once every 3 weeks), standard of care plus radiotherapy, standard of care plus abiraterone (oral 1000 mg abiraterone once daily plus oral 5 mg prednisone twice daily), or standard of care plus radiotherapy plus abiraterone. Neither the investigators nor the patients were masked to treatment allocation. The coprimary endpoints were radiographic progression-free survival and overall survival. Abiraterone efficacy was first assessed in the overall population and then in the population who received androgen deprivation therapy with docetaxel as standard of care (population of interest). This study is ongoing and is registered with ClinicalTrials.gov, NCT01957436., Findings: Between Nov 27, 2013, and Dec 20, 2018, 1173 patients were enrolled (one patient subsequently withdrew consent for analysis of his data) and assigned to receive standard of care (n=296), standard of care plus radiotherapy (n=293), standard of care plus abiraterone (n=292), or standard of care plus radiotherapy plus abiraterone (n=291). Median follow-up was 3·5 years (IQR 2·8-4·6) for radiographic progression-free survival and 4·4 years (3·5-5·4) for overall survival. Adjusted Cox regression modelling revealed no interaction between abiraterone and radiotherapy, enabling the pooled analysis of abiraterone efficacy. In the overall population, patients assigned to receive abiraterone (n=583) had longer radiographic progression-free survival (hazard ratio [HR] 0·54, 99·9% CI 0·41-0·71; p<0·0001) and overall survival (0·82, 95·1% CI 0·69-0·98; p=0·030) than patients who did not receive abiraterone (n=589). In the androgen deprivation therapy with docetaxel population (n=355 in both with abiraterone and without abiraterone groups), the HRs were consistent (radiographic progression-free survival 0·50, 99·9% CI 0·34-0·71; p<0·0001; overall survival 0·75, 95·1% CI 0·59-0·95; p=0·017). In the androgen deprivation therapy with docetaxel population, grade 3 or worse adverse events occurred in 217 (63%) of 347 patients who received abiraterone and 181 (52%) of 350 who did not; hypertension had the largest difference in occurrence (76 [22%] patients and 45 [13%], respectively). Addition of abiraterone to androgen deprivation therapy plus docetaxel did not increase the rates of neutropenia, febrile neutropenia, fatigue, or neuropathy compared with androgen deprivation therapy plus docetaxel alone., Interpretation: Combining androgen deprivation therapy, docetaxel, and abiraterone in de novo metastatic castration-sensitive prostate cancer improved overall survival and radiographic progression-free survival with a modest increase in toxicity, mostly hypertension. This triplet therapy could become a standard of care for these patients., Funding: Janssen-Cilag, Ipsen, Sanofi, and the French Government., Competing Interests: Declaration of interests KF reports consulting fees from Amgen, AstraZeneca, Astellas, Bayer, CureVac, Janssen, Novartis, Orion, Pfizer, and Sanofi; honoraria from AstraZeneca, Astellas, Bayer, Janssen, Novartis, and Sanofi; and participation on a Data Safety Monitoring Board for Lilly. JC reports grants from AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim, Esperia, Bristol Myers Squibb, Clovis Oncology, Cougar Biotechnology, Deciphera Pharmaceuticals, Exelixis, F Hoffmann-La Roche, Genentech, GlaxoSmithKline, Incyte Corporation, Janssen-Cilag, Karyopharm Therapeutics, Laboratoires Leurquin Mediolanum, Lilly, Medimmune, Millennium Pharmaceuticals, Nanobiotix, Novartis Farmacéutica, Pfizer, Puma Biotechnology, Sanofi-Aventis, SFJ Pharma, and Teva Pharma; consulting fees from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi; honoraria from Bayer, Johnson & Johnson, and Astellas Pharma; payment for expert testimony from Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi; and participation on a Data Safety Monitoring Board or Advisory Board for Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Johnson & Johnson, MSD Oncology, Novartis, Pfizer, Roche, and Sanofi. GR reports honoraria from Astellas Pharma, AstraZeneca, Janssen, Ipsen, and Sanofi; and support for attending meetings from Janssen and Ipsen. RM reports grants from Bayer; honoraria from MSD; and participation on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb, Clovis, Janssen, MSD, and Pfizer. AF reports honoraria from Astellas Pharma, AstraZeneca, Janssen, Novartis, and Sanofi. BT reports grants from Ferring and Bayer; personal fees from Amgen, Astellas Pharma, Ferring, Bayer, Novartis, Myovant, and Sanofi; and non-financial support from Astellas and Janssen. SS reports grants from Astellas Pharma, AstraZeneca, and Janssen; and consulting fees, honoraria, and receipt of equipment from Astellas Pharma, AstraZeneca, Bayer, Ipesen, Janssen, and Takeda. DB reports honoraria from Amgen, Astellas Pharma, Bayer, Janssen, and Novartis. GK reports grants from Astellas Pharma and Janssen; and participation on an Advisory Board and honoraria from Astellas Pharma, AstraZeneca, Janssen, and Sanofi. FC reports honoraria from Bristol Myers Squibb and MSD; and participation on an Advisory Board for AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, and Ipsen. AT-V reports grants from Bayer, Ipsen, and Pfizer; and consulting fees or honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Ipsen, JNJ, Novartis, MSD, and Roche. BL reports honararia from Janssen; and support for attending meetings from Astellas Pharma, Janssen, and Pfizer. AR reports honoraria from Astellas Pharma, Bayer, and Janssen; and support for attending meetings from Astellas Pharma, Ipsen, and Janssen. NM reports honoraria from Astellas Pharma, Bayer, Ipsen, and MSD. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective : Our objective was to develop a radiomics model based on magnetic resonance imaging (MRI) and contrast-enhanced computed tomography (CE-CT) to predict pathological complete response (pCR) to neoadjuvant treatment in locally advanced rectal cancer (LARC). Material: All patients treated for a LARC with neoadjuvant CRT and subsequent surgery in two separate institutions between 2012 and 2019 were considered. Both pre-CRT pelvic MRI and CE-CT were mandatory for inclusion. The tumor was manually segmented on the T2-weighted and diffusion axial MRI sequences and on CE-CT. In total, 88 radiomic parameters were extracted from each sequence using the Miras© software, with a total of 822 features by patient. The cohort was split into training (Institution 1) and testing (Institution 2) sets. The ComBat and Synthetic Minority Over-sampling Technique (SMOTE) approaches were used to account for inter-institution heterogeneity and imbalanced data, respectively. We selected the most predictive characteristics using Spearman's rank correlation and the Area Under the ROC Curve (AUC). Five pCR prediction models (clinical, radiomics before and after ComBat, and combined before and after ComBat) were then developed on the training set with a neural network approach and a bootstrap internal validation ( n = 1000 replications). A cut-off maximizing the model's performance was defined on the training set. Each model was then evaluated on the testing set using sensitivity, specificity, balanced accuracy (Bacc) with the predefined cut-off. Results: Out of the 124 included patients, 14 had pCR (11.3%). After ComBat harmonization, the radiomic and the combined models obtained a Bacc of 68.2% and 85.5%, respectively, while the clinical model and the pre-ComBat combined achieved respective Baccs of 60.0% and 75.5%. Conclusions: After correction of inter-site variability and imbalanced data, addition of radiomic features enhances the prediction of pCR after neoadjuvant CRT in LARC.

Non-clear cell renal cell carcinomas (nccRCC) represent a highly heterogeneous group of kidney tumors, consisting of the following subtypes: papillary carcinomas, chromophobe renal cell carcinoma, so-called unclassified carcinomas or aggressive uncommon carcinomas such as Bellini carcinoma, renal cell carcinoma (RCC) with ALK rearrangement or fumarate hydratase-deficient RCC. Although non-clear cell cancers account for only 15 to 30% of renal tumors, they are often misclassified and accurate diagnosis continues to be an issue in clinical practice. Current therapeutic strategy of metastatic nccRCC is based primarily on guidelines established for clear cell tumors, the most common subtype, however this approach remains poorly defined. To date, published clinical trials for all histological nccRCC subtypes have been collectively characterized into one group, in contrast to clear cell RCC, and given the small numbers of cases, the interpretation of study results continues to be challenging. This review summarizes the available literature for each nccRCC subtype and highlights the lack of supportive evidence from prospective clinical trials and retrospective studies. Future trials should evaluate treatment approaches which focus on a specific histological subtype and progress in treating nccRCC will be contingent on understanding the unique biology of their individual histologies., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce., Methods: Clinical data were searched through PubMed database until April 2020 according to PRISMA criteria. Efficacy, safety and pharmacokinetic (PK) assessment of ST were reported., Results: Among 270 references, 56 reports were evaluated in full text: 41 were included for efficacy and 42 for safety analysis (sunitinib n = 68, bevacizumab n = 6, everolimus n = 28, temsirolimus n = 17, sorafenib n = 55, axitinib n = 13, pazopanib n = 13, nivolumab n = 18, cabozantinib n = 0, lenvatinib n = 0, and ipilimumab n = 0). Twelve of the reports included PK assessment among dialyzed patients. Hemodialysis did not seem to modify the expected efficacy and safety of each compound among patients undergoing hemodialysis. PK assessments were not modified in comparison with a population not undergoing dialysis., Conclusion: Targeted and Immune therapies seem to be effective and can be used among patients undergoing hemodialysis. Due to frailty and comorbidities associated to chronic hemodialysis enhanced vigilance for these therapies within this specific population is recommended. Dedicated prospective clinical trials would definitely help to obtain data with a higher level of evidence., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Klajer E.: Pfizer and Ipsen Garnier L.: No conflict of interest Goujon M.: BMS and Ipsen Schurmann-Constans F.: Ipsen, Novartis, PfizerMery B.: No conflict of interest N Guyen Tan Hon: No conflict of interest Mouillet G: BMS Ipsen, Novartis, Pfizer, and Roche, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Management of non metastatic castrate resistant prostate cancer is challenging for clinicians due to the heterogeneity of the disease and to the scarce clinical data available in this setting. Recent results obtained with the new generation hormone therapies (NGHT) apalutamide and enzalutamide bring a new perspective for the treatment strategy. The authors present here a systematic review of the treatment options., (Copyright © 2018. Published by Elsevier Ltd.)

The majority of patients with prostate cancer who later develop lethal metastatic disease have high-risk localized disease at presentation, emphasizing the importance of effective treatment strategies at this stage. Multimodal treatment approaches that combine systemic and local therapies offer a promising strategy for improving the clinical outcomes of patients with high-risk localized prostate cancer. Combinations of neoadjuvant and adjuvant chemotherapy, hormonal therapy, or chemohormonal therapy are considered to be the standard of care in most solid tumours and should be investigated in the future for the treatment of prostate cancer to improve patient outcomes. However, although the combination of androgen deprivation therapy and radiotherapy is a standard of care in high-risk localized or locally advanced prostate cancer, the benefit of chemotherapy or chemohormonal therapy has yet to be demonstrated outside of the metastatic setting. Moreover, the benefit of neoadjuvant and/or adjuvant systemic therapies in combination with radical prostatectomy has not been proved. The development of next-generation hormonal agents, which have been approved for the treatment of castration-resistant prostate cancer, offers further therapeutic possibilities that are being assessed in early-phase clinical trials.

Emerging evidence from population-based and retrospective series suggests a potential improvement of clinical outcomes in metastatic prostate cancer. Moreover, metastasis-directed treatment has shown encouraging results in this setting. There is an increasing interest in exploring the potential of local therapies in advanced prostate cancer, but this has rarely been specifically addressed in the castration-resistant state, whether non-metastatic or metastatic. A review of relevant articles was performed on the oncologic benefit of local treatment of the primary tumor or metastasis-targeted treatment in castration-resistant prostate cancer patients. The main goal of this strategy is to delay introduction of a new systemic agent to maintain quality of life and potentially to limit resistance. Further investigation is required to provide high-level evidence for the oncologic benefit of this treatment modality., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: We report two cases of Bazex-Dupré-Christol syndrome in a father and daughter with divergent clinical pictures at two different ages., Patients and Methods: A 6-month-old infant was seen with her parents for profuse milia which had appeared when she was 2 months old and persisted ever since. The remainder of the dermatological examination and the psychomotor development tests were normal. Dermatological examination of the father showed atrophic cutaneous lesions with follicular punctuated depressions (like "ice-pick marks") on the back of the hands and the forearms. He also presented diffuse hypotrichosis and hypohydrosis. In addition, he had a history of basal cell carcinoma with surgery before the age of 35 years. Finally, questioning revealed the existence of numerous similar cases in the family. In view of all these factors, a diagnosis of Bazex-Dupré-Christol syndrome was made., Discussion: Bazex-Dupré-Christol syndrome is a genodermatosis with X-linked dominant inheritance. Diagnosis is based on association of follicular atrophoderma, congenital hypotrichosis, hypohydrosis and early basal cell carcinoma. Other than fragile skin and cosmetic blemishes, these tumors are the only complication of the disease and require regular dermatological surveillance and solar protection. Common initial signs of the disease are abnormally profuse milia in neonates that tend to persist throughout childhood. Several differential diagnoses may be evoked.

Unlabelled: Diagnosis of pustular dermatosis occurring during the first days of life is based on clinical findings. Erythema toxicum neonatorum (ETN) is the more frequent benign self limiting eruption in the newborn., Case Reports: Three cases of ETN with localized pustules to the genitals and perineal area are described., Comment: When encountering a newborn with a localized pustulosis rash, it is important to separate benign condition as ETN from those that require prompt diagnosis and therapy. Atypical ETN and pustular dermatosis due to bacterial or viral infections or inflammatory diseases (e.g., eosinophilic pustulosis) can be differentiated by cytological and bacterial samples.