Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

Epidemiology of breast cancer in women based on diagnosis data from oncologists and senologists in Algeria.

BACKGROUND: Breast cancer (BC) is a major health issue threatening women's life. No reliable epidemiological data on BC diagnosed by oncologists/senologists are available in Algeria. METHODS: The BreCaReAl study, a non-interventional prospective cohort study, included adult women with confirmed BC in Algeria. Disease incidence, patients and disease characteristics, treatment patterns, and mortality rate were recorded up to 12 months of follow-up. RESULTS: Overall, 1,437 patients were analysed: median age was 48 [41;57] years and 337 (23.5%) women had a family history of BC. BC incidence was 22.3 (95% CI: 21.5; 23.2) cases per 100,000 inhabitants over 8 months. Delayed diagnosis was reported in 400 (29.2%) patients. First line of treatments were mainly chemotherapy and surgery. Twenty-eight serious adverse events were reported including 10 (37.0%) events which led to death. Mortality rate reached 3.2% at 12 months CONCLUSION: A delayed diagnosis highlights the importance of implementing more effective screening strategies.

The EcoChip 2: An Autonomous Sensor Platform for Multimodal Bio-environmental Monitoring of the Northern Habitat.

This paper presents the EcoChip 2, an autonomous multimodal bio-environmental sensor platform for the monitoring of microorganisms in the northern habitat. The EcoChip 2 prototype includes an array of 96-wells for the continuous monitoring of microbiological growth through a multichannel electrochemical impedance analyzer circuit. In addition, the platform includes luminosity, humidity, temperature sensors and monitoring. The developed electronic board uses an ultra-low-power microcontroller unit, a custom power management unit, a low-power wireless ISM-2.45 GHz transceiver, and a flash memory to accumulate and store the sensor data over extended monitoring periods. When a wireless base station is placed within the transmission range of the EcoChip 2, an embedded low-power wireless transceiver transmits the 96-wells impedance data and the other sensor data stored in the flash memory to the user interface. We present the measured performance of the prototype, along with laboratory test results of bacterial growth measurements inside the 96 wells in parallel. We show that the EcoChip 2 can successfully measure the impedances associated with bacterial growth over several hours using an excitation frequency of 2 kHz with power consumption of 114.6 mW under operating mode.

[Inherited kidney stones: A nephrology center experience]. / Lithiase urinaire héréditaire : expérience d'un service de néphrologie.

INTRODUCTION: Genetic factors must be considered in etiological diagnosis of urinary lithiasis. The aim of this study was to determine clinical, metabolic characteristics and the progression of hereditary urinary lithiasis in our patients. METHODS: A retrospective study was conducted between 2008 and 2018 and 60 patients were included. Patients were referred to our department from pediatrics departments to be followed-up in adulthood in 9 cases, for etiological investigation in 42 cases and for chronic renal failure in 9 cases. RESULTS: Thirty-five men and twenty-five women were enrolled in this study with a M/F sex ratio equal to 1.4. The mean age at the time of diagnosis of the hereditary character of the urinary lithiasis was 28.6years (3months-63years). The average delay between the onset of the lithiasis disease and the etiological diagnosis was 8years (0-42years). We noted 31 cases of cystinuria, 18 cases of primary hyperoxaluria type 1 with two mutations (I244T in 14 cases, 33-34 Insc in 23 cases) and 11 cases of renal tubulopathy. Fourteen patients were affected with chronic renal failure, of which five were in the end-stage renal disease. Crystalluria was positive in 62% of cases. The morpho-constitutional analysis of stones was performed in 37 cases and it contributed to the diagnosis in 29 cases. After an average follow-up of 16years, we noted normal renal function in 42 cases, chronic renal failure in 7 cases, hemodialysis in 10 cases all with primary hyperoxaluria and transplantation in 1 case. CONCLUSION: The etiological diagnosis of hereditary urinary lithiasis in our study was made with considerable delay. Cystinuria was the most frequent etiology and primary hyperoxaluria was the most serious affection. LEVEL OF EVIDENCE: 4.

[Therapeutic monoclonal antibodies in oncology]. / Anticorps monoclonaux thérapeutiques en cancérologie.

Advances in bioengineering have lead to the possibility to conduct large scale production of monoclonal antibodies (MoAB) and to reduce progressively the murine component from 30% (chimeric MoAB) to 5% (humanized MoAB) to 0% (human MoAB). Three types of extracellular components are targeted in solid tumours: (1) Growth factors with transmembrane tyrosine kinase receptors either of tumour cells (IGF1) or endothelial cells (Bevacizumab). Bevacizumab has activity additive to that of chemotherapy in advanced colorectal, non squamous lung, ovarian, metastatic breast cancers and glioblastomas; (2) Extracellular domain of those transmembrane receptors: EGFR in colorectal cancer if no activating of KRAS with cetuximab and panitumumab, head and neck carcinomas with radiotherapy, and probably squamous lung cancers. Anti-ERBB2 MoAb are now a constitutive part of therapy of ERBB2 positive breast cancers at any stage; (3) Differentiation cluster regulating relationship ot tumour and stromal cells and in particular immunologic effectors. This is the case of anti-CTLA4 MoAB ipilimumab which activates and amplifies immunological cytotoxic response against melanoma with improved survival. These activities are achieved to the expense of class, target related toxicity conditioned by expression of the target on normal cells and or mechanism of action (immunological toxicity with ipilimumab). Of note a synergistic or additive activity with valid treatment regimens of targeted cancers and now targeted small molecules.

Increased urinary type II collagen C-telopeptide levels in Tunisian patients with knee osteoarthritis.

UNLABELLED: Osteoarthritis is characterized by a progressive degeneration of articular cartilage and loss of joint function. Clinical assessment of osteoarthritis is hampered by the lack of accurate measures of disease and disease progression, especially during the early stage. BACKGROUND: To investigate urinary C-telopeptide fragments of type II collagen (CTX-II) levels in knee osteoarthritis in the Tunisian population compared with controls and to assess the association between this biomarker and radiological signs. METHODS: One hundred and twenty five female patients with knee osteoarthritis, aged 53.6 +/- 7.6 years with disease duration of 3.6 +/- 3.8 years and 57 female age-matched controls underwent Lyon Schuss X-ray exams. Two experienced readers independently measured the joint space width (JSW) and classified each knee for severity using the Kellgren/Lawrence scale. The urinary concentration of CTX-II was measured by a competitive ELISA. RESULTS: The levels of urinary CTX-II were significantly higher in knee osteoarthritis patients compared with controls (323.98 vs 218.04 microg/mol creatinine). A weak and non significant association between the CTX-II level and JSW was found. The significant correlations were observed between age and CTX-II in both groups and between BMI and CTX-II only in controls. CONCLUSIONS: Analysis of CTX-II in urine samples of Tunisian patients with knee osteoarthritis provided a sensitive method to detect increased degradation of collagen type II in patients with osteoarthritis.

[Study of cardiovascular risk factors in Tunisian patients with recent type 2 diabetes]. / Étude des facteurs de risque cardiovasculaire chez le diabétique de type 2 Tunisien récemment découvert.

OBJECTIVE: To study the frequency of silent myocardial ischemia (SMI) in Tunisian patients with recent type 2 diabetes and identify cardiovascular risk factors directly in relation with SMI. PATIENTS AND METHODS: One hundred and twenty diabetics and sixty healthy people have benefited from blood sampling, electrocardiogram and exercise test. RESULTS: The frequency of SMI was 21% in diabetics and 3% in healthy people (P=0.01). Obesity and hypertension were higher in diabetics than in healthy people (P=0.001 and P<10(-4)). Using unvaried analysis for risk factors with the presence of SMI in diabetics, we found that age greater than 60 yrs, male sex, sedentary and smoking were significantly correlated with SMI; respectively P=0.004, 0.01, 0.009 and 0.03. The SMI was found in 37% of diabetics with high blood pressure vs 8% in diabetics with normal blood pressure and was correlated with hypertriglyceridemia, hypoHDLemia and microalbuminuria. Patients with SMI had at least two cardiovascular risk factors apart from diabetes among those: age greater or equal to 60 yrs, male sex, smoking, hypertension, dyslipidemia and family history of early coronaropathy. Chronic inflammation and hyperhomocysteinemia were significantly correlated to SMI; OR=4.2 and 3.8. In addition, SMI was found in one diabetic over three who had bad glycemic control. Using multivariate analysis, only age greater or equal to 60 yrs, smoking, hypertension, hyperhomocysteinemia and hypertriglyceridemia were risk factors directly in relation with SMI in type 2 diabetes. CONCLUSION: The assessment of global cardiovascular risk from the moment of discovering type 2 diabetes and the early screening of SMI should be necessary.

[Treatment of advanced and/or metastatic colorectal cancer with bevacizumab in combination with oxaliplatin-based chemotherapy (Folfox7 regimen)]. / Bevacizumab plus oxaliplatine, acide folinique et 5-fluoro-uracile (Folfox7) en première ligne de traitement des cancers colorectaux évolués et/ou métastatiques.

INTRODUCTION: Fundamental research identified new therapy targets implicated in tumor proliferation and angiogenesis which lead to the development of several targeted therapies. Currently, three drugs are used in the treatment of advanced colorectal cancer, cetuximab and panitumumab, two anti epidermal growth factor receptor, and bevacizumab, an anti vascular endothelial growth factor. PATIENTS AND METHODS: We evaluated a treatment with oxaliplatin-based chemotherapy (Folfox7 regimen) and bevacizumab in patients with locally advanced and/or metastatic colorectal cancer. Objectives of the study are the evaluation of the efficacy, toxicity, progression free survival, overall survival and tumor cell expression of the vascular endothelial growth factor by immunochemistry. RESULTS: 47 patients are included in the study during the period between April 2005 and June 2007; 28 men and 19 women. After six cycles of treatment, we achieved 67.3% of objectives responses and 76% of tumor control. The median progression free survival evaluated was 12 months (9.3-14.6 months) and median overall survival 18 months (9-26.9 months). The immunochemistry study of 46 tumours of the study achieved the following results: 13% (0), 17.4% (1+), 23.9% (2+) and 45.7% (3+). A correlation between the vascular endothelial growth factor expression, therapeutic responses and survival has been demonstrated but the difference was not significant in term of survival. Both chemotherapy toxicity and bevacizumab related toxicity are acceptable in our study. CONCLUSION: The fact that vascular endothelial growth factor expression is common in more than 80% of colorectal cancers, lead to recommend the systematic use of bevacizumab with chemotherapy in the treatment of advanced colorectal cancer.

A randomized phase II trial of irinotecan in combination with infusional or two different bolus 5-fluorouracil and folinic acid regimens as first-line therapy for advanced colorectal cancer.

BACKGROUND: Three different therapeutic regimens of irinotecan (CPT-11) in combination with 5-fluorouracil (5-FU) and folinic acid (FA) were evaluated for efficacy and safety in the first-line therapy of advanced colorectal cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive intravenously either: CPT-11 125 mg/m(2), FA 20 mg/m(2) followed by 5-FU 500 mg/m(2) bolus, weekly for 4 weeks (arm A, Saltz regimen); or CPT-11 180 mg/m(2) day 1 then FA 200 mg/m(2) over 2 h and 5-FU 400 mg/m(2) bolus and 5-FU 600 mg/m(2) 22-h infusion on days 1 and 2, every 2 weeks (arm B, Douillard regimen); or CPT-11 350 mg/m(2) (days 1 and 43) alternating with FA 20 mg/m(2)/day followed by 5-FU bolus 425 mg/m(2)/day during 5 days (days 22-26) (arm C, Mayo Clinic regimen). RESULTS: A total of 154 patients were included in the study (arm A, 51 patients; arm B, 53; arm C, 50). Overall response rates for the intention-to-treat populations were 33% [95% confidence interval (CI) 21% to 48%], 42% (95% CI 28% to 56%) and 30% (95% CI 18% to 45%) for arms A, B and C, respectively. Median times to progression were 6, 8 and 7 months for arms A, B and C, respectively. Median survival times were 15, 12 and 17 months for arms A, B and C, respectively. Overall response rates for the evaluable patient populations were 40% (95% CI 24% to 58%) in arm A, 44% (95% CI 29% to 60%) in arm B and 31% (95% CI 17% to 47%) in arm C. Neutropenia was the main serious adverse event in arms A (30% of patients) and C (22% of patients) but occurred in only 8% of patients in arm B. Delayed diarrhea was the main severe adverse event for the three regimens, from 15% to 22%. CONCLUSION: All three regimens were highly active. The biweekly combination of CPT-11 and 5-FU/FA (arm B) was notable for its low incidence of grade 3/4 neutropenia. The incidence of grade 3/4 delayed diarrhea was equivalent for the three treatment arms.

Haemoglobin D-Ouled Rabah among the Mozabites: a relevant variant to trace the origin of Berber-speaking populations.

We have studied haemoglobin (Hb) variants and blood groups (ABO, RH, and Kell) in 598 children from the Berber population of the Mzab. Hb D-Ouled Rabah, considered as a private marker of the Kel Kummer Tuaregs, and Hb C were found at the same gene frequency (0.015). Haplotype analysis suggests a single origin to the Hb D mutation. Genetic distances calculated from the blood group data cluster Mozabites and Tuaregs with the other Berber-speaking groups, Arabic-speaking populations being more distant. But, we found no specific relationship between Mozabites and Kel Kummers. Tuaregs in general exhibit features that tend to differentiate them from other Berber-speaking groups. Hb D-Ouled Rabah may be specific of Berber-speaking populations.

[Xeroderma pigmentosum. A study in 40 Algerian patients]. / Xeroderma pigmentosum. Etude de 40 malades algériens.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rate autosomal recessive disorder related to DNA repair defects. Recently, modifications of oncogenes and mutations of the p53 suppressor gene have been reported in skin tumors of XP patients. The purpose is to study, through a series of 40 patients admitted to the Dermatologic Clinic of Algiers, the characteristics of XP in Algeria. PATIENTS AND METHODS: For each patient, familiarity, clinical and biological examinations and therapeutic results were studied. Biological studies have been axed mainly on analysis of DNA extracted from skin tumors of 18 patients to detect oncogene modifications by Southern blot and hybridization. A technic, based on single strand DNA conformation polymorphism (SSCP), has been carried out to detect rapidly mutations on the p53 gene. RESULTS: A consanguinity in the first degree is noted in 95 p. 100 of cases and a familiarity in 63 p. 100 of cases. The median age of patients is 10 years; sex ratio is close to one; 32 patients (80 p. 100) are classic XP and 8 (20 p. 100) are XP variant. In 18 tumors analysed, the Ha-ras gene is amplified and/or modified in 50 p. 100 of cases. Only 3 tumors (16.6 p. 100) show mutations of the p53 gene (transitions C-T). Surgical treatment isolated or associated to polychemotherapy permitted to resolve tumors in 75 p. 100 of cases. DISCUSSION: In Algeria, XP are mainly classic with a particularly high frequency of occular (62 p. 100) and neurological manifestations (62 p. 100). Genetic studies confirm modifications of the Haras gene in direct relation with unrepaired UV lesions in classic XP and mutations of the p53 tumor suppressor gene characteristic of mutation spectra induced by UV. Surgery is the treatment of choice for tumors; polychemotherapy is an alternative in advanced cases.

[Hodgkin disease, clinical stages IA-IIB: evaluation of the value of cisplatin. Preliminary results]. / Maladie de Hodgkin, stades cliniques IA-IIB: évaluation de l'intérêt du cisplatine. Résultats préliminaires.

Cisplatinum is highly effective in numerous solid tumors and was evaluated in Hodgkin's disease clinical stages (CS) I/II. Sixty-five patients (43 male, 22 female; median age 25, with 12 patients under 16: CS IA-IIA 41, IB 5, IIB 19) were randomly assigned to one of the following arms (PAF87 protocol): 3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine with methylprednisolone) cycles (ABVD arm) or 3 ABVD plus cisplatinum cycles (ABVD-Plt arm) followed by radiotherapy (RT); extended field (40 Gy) RT with a short paraaortic field including the spleen (30 Gy) was then administered in the ABVD arm; extended field (30 Gy) without lombosplenic port prophylaxis. RT was administered in ABVD-Plt arm when patients were in complete remission (CR) after chemotherapy (CT). Median follow-up was 35 months (6-62 months). During CT, 1 patient (ABVD-Plt) died from viral meningo-encephalitis; five patients (1 ABVD, 4 ABVD-Plt) stopped treatment because of emesis, of whom three receiving only 1.5-2.5 (ABVD-Plt) cycles, are still in CR after 13-60 months. Fifty-five patients (27 ABVD-Plt) were in CR after CT. Among the 27 ABVD-Plt patients, all in CR after RT, two died (one from myocardial infarction and one from immunoblastic lymphoma); one patient from the ABVD arm died from gastro-intestinal hemorrhage in 1st CR. No ABVD-Plt patient relapsed; 1 ABVD patient relapsed in non-irradiated area. At five years, actuarial survival/relapse-free survival was 96.1/90% and 88.2/100% for ABVD and ABVD-Plt patients, respectively.