Irreversible electroporation to bring initially unresectable locally advanced pancreatic adenocarcinoma to surgery: the IRECAP phase II study.

OBJECTIVES: The aim of the IRECAP study was to evaluate the rate of locally advanced pancreas cancer patients (LAPC) who could undergo R0 or R1 surgery after irreversible electroporation (IRE). MATERIALS AND METHODS: IRECAP study is a phase II, single-center, open-label, prospective, non-randomized trial registered at clinicaltrials.gov (NCT03105921). Patients with LAPC were first treated by 3-month neo-adjuvant chemotherapy in order to avoid inclusion of either patients with LAPC having become resectable after chemotherapy or patients with rapid disease progression. In cases of stable disease, IRE was performed percutaneously under CT guidance. Surgery was planned between 28 and 90 days after IRE. Tumor specimens were studied to evaluate the resection margins (R0/R1/R2). RESULTS: Six men and 11 women were included (median age 61 years, range 37-77 years). No IRE-related death was observed. Ten patients (58%, 10/17) experienced 25 serious adverse events related to IRE. Four patients progressed between IRE and surgery and were excluded from surgery. Thirteen patients were finally operated, six withheld for pancreas resection, three for diffuse peritoneal carcinosis, two for massive vascular entrapment, and one for hepato-cellular carcinoma not diagnosed before surgery. Rate of R1-R0 was 35% (n = 6/17). Median overall survival was 31 months (95% CI; 4-undefined) for the six patients with R0/R1 resection and 21 months (95% CI; 4-25) for the 11 patients without resection or R2 resection (logrank p = 0.044). CONCLUSION: After neoadjuvant chemotherapy, IRE could provide R0 or R1 resection in 35% of LAPC, which seems to be associated with higher OS. CLINICAL RELEVANCE STATEMENT: After induction chemotherapy, stable locally advanced pancreatic cancers can be treated by irreversible electroporation, which could lead to a secondary 35% rate of R0 or R1 surgical resection which may be associated with a significantly higher overall survival. KEY POINTS: • In cases of unresectable LAPC (locally advanced pancreatic cancer), percutaneous irreversible electroporation (pIRE) is feasible (100% success rate of the procedure), but is associated with a 58% rate of grade 3-4 adverse events. • In patients with unresectable LAPC, pIRE could lead 35% of patients to R0-R1 surgical resection. • From IRE, median overall survival was 31 months (95% CI; 4-undefined) for the patients with R0/R1 resection and 21 months (95% CI; 4-25) for the patients without resection or R2 resection (logrank p = 0.044).

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

BACKGROUND: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP). OBJECTIVE: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead. MATERIALS AND METHODS: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up. RESULTS: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001). CONCLUSION: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.

Serious adverse effects occurring after chemotherapy: A general cancer registry-based incidence survey.

AIMS: Pharmaco-epidemiological surveys enable the frequency of serious adverse effects-and also the determining factors of their occurrence and seriousness-to be quantified. Few studies systematically gathering post-chemotherapy adverse effects data have been conducted. The objective was to assess the incidence of post-chemotherapy serious adverse effects on the basis of cancer registry data. METHODS: The population was composed of new invasive cancer cases, with the exception of haematopoietic tumours and cutaneous carcinomas. These cancers were identified in 2012 among patients living at the time of diagnosis in a region covered by a general cancer registry and by a French regional pharmacovigilance centre, and treated with neo-adjuvant and/or adjuvant first-intention chemotherapy, followed or not by radiotherapy. The study was based on a sample of 1000 patients from the registry, followed by the collection of serious adverse effects and the required information to constitute a pharmacovigilance file. RESULTS: Chemotherapy was associated with a particularly high incidence of serious adverse effects, affecting 44.5% (41.4-47.5%) of the patients. The highest incidence rates were observed when patients were exposed to topo-isomerase II inhibitors such as etoposide and bleomycin (69.2%), vinca-alkaloids (66.7%), topo-isomerase I inhibitors (54.5%) and platinum derivatives (52.0%). The clinical context was also linked to incidence, especially in case of metastases (53.3%) and comorbidities (51.3%). Substantial differences were found according to localisation, with a particularly high incidence in bronchial-pulmonary cancers (59.0%). CONCLUSION: The high overall incidence rate of serious adverse effects should motivate a reinforcement of information about drug toxicities and improve knowledge by drawing on patient reporting.

Information sur le risque familial de cancer colorectal. Regards croisés sur l'efficacité d'une intervention personnalisée.

OBJECTIVE: Information on risk levels is an essential part of the prevention of colorectal cancer (CRC). The objective of this article is to describe a tailored intervention carried out to inform the protagonists about the high risk of CRC due to family history and then to understand, through an interdisciplinary analysis, the mechanisms implemented during the intervention. METHOD: A randomized trial design was applied. The primary outcome was the colonoscopy uptake. The intervention concerned firstly the index patients with CRC or adenoma to advise and accompany them in the transmission of information about the elevated risk for their siblings. The siblings received tailored counselling carried out by a preventive nurse, by telephone then by mail. Epidemiological, linguistic and sociological cross-analyzes were carried out to understand the impact of the intervention. RESULTS: Colonoscopy rate was 56.3% in the intervention group, 35.4% in the control group (P = 0.0027; 304 siblings). The linguistic analysis of recorded nurse's interventions showed that, following the intervention (N = 59), the prevention themes were better assimilated while they remained vague and questioned in the discourse of the control siblings who had carried out the colonoscopy (N = 8). That was confirmed by the sociological analysis (four families) which also revealed the importance of information received from a health professional and of communication within families. CONCLUSION: The study showed the impact of transmission of information to convince siblings at high risk of CRC to carry out colonoscopy.

[Family risk information for colorectal cancer. Perspectives on the effectiveness of a tailored intervention] / Information sur le risque familial de cancer colorectal. Regards croisés sur l'efficacité d'une intervention personnalisée.

OBJECTIVE: Information on risk levels is an essential part of the prevention of colorectal cancer (CRC). The objective of this article is to describe a tailored intervention carried out to inform the protagonists about the high risk of CRC due to family history and then to understand, through an interdisciplinary analysis, the mechanisms implemented during the intervention. METHOD: A randomized trial design was applied. The primary outcome was the colonoscopy uptake. The intervention concerned firstly the index patients with CRC or adenoma to advise and accompany them in the transmission of information about the elevated risk for their siblings. The siblings received tailored counselling carried out by a preventive nurse, by telephone then by mail. Epidemiological, linguistic and sociological cross-analyzes were carried out to understand the impact of the intervention. RESULTS: Colonoscopy rate was 56.3% in the intervention group, 35.4% in the control group (P = 0.0027; 304 siblings). The linguistic analysis of recorded nurse's interventions showed that, following the intervention (N = 59), the prevention themes were better assimilated while they remained vague and questioned in the discourse of the control siblings who had carried out the colonoscopy (N = 8). That was confirmed by the sociological analysis (four families) which also revealed the importance of information received from a health professional and of communication within families. CONCLUSION: The study showed the impact of transmission of information to convince siblings at high risk of CRC to carry out colonoscopy.

Aggressive primary treatments with favourable 5-year survival for screen-interval breast cancers.

BACKGROUND: To assess the impact of the participation in screening programme according to the mode of detection on the early diagnosis, treatment, and specific survival outcomes in women with breast cancer. METHODS: Women diagnosed with invasive breast cancer in Poitou-Charentes region (France) between 2008 and 2009 were classified into three groups, using data linkage of cancer registry, vital statistics and French organized screening programme: the screening programme (SP), interval cancer (IC), and non-screening programme detected cancer (NSP) groups. Specific survival rates were analysed using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Among 1613 patients, 65.7% (n = 1059) participated in a screening programme. The interval cancer rate was 17.1% (n = 181). Tumours in the IC group were diagnosed at a more advanced stage, i.e. with further regional lymph node metastasis or local spread, than those in the SP group (p < 0.001), but with significantly fewer metastases at diagnosis than in the NSP group (p < 0.001). ICs underwent more aggressive primary treatments than the two other groups, with 28% of radical mastectomy and 67% undergoing chemotherapy. The five-year survival rate for IC group were 92.0% (95% CI, 89.9-94.0%). CONCLUSIONS: Interval cancers had more aggressive features than screen-detected cancers but were diagnosed at a less advanced stage compared to non-screen detected cancers. Despite having cancers missed by the screening programme, women who participate in the screening process seem to benefit from early treatment. These results must be confirmed with long-term follow-up.

Age-related health care disparities in multiple myeloma.

Age is a well-known factor in solid tumours linked to lower adherence to guidelines. Scarce data exist for haematologic malignancies such as multiple myeloma (MM). The aim of the study was to investigate the relationships among age, adherence to guidelines in MM, and overall survival (OS).The Poitou-Charentes cancer registry has exhaustively registered incident cases of MM from 2008 to 2010. Diagnosis, staging, prognosis, and first-line treatment were compared to the international guidelines. Three hundred and sixty-seven patients aged 36 to 93 years were included. Compliance to diagnostic procedure was 98%, staging 62%, prognosis 30%, and first-line treatment 89%. Cytogenetic analysis was compliant in 37%. Younger age was the strongest factor associated with compliant provision of care (odds ratio 14.4 [6.1-33.8] for <66 years and 2.3 [0.9-6.1] for 66-74 years; P < .0001). The second independent factor was active versus smouldering myeloma (odds ratio 3.5 [1.6-7.3]; P = .0009). Adherence to guidelines is related with OS in multivariate analysis hazard ratio: 1.6 [1.0-2.5]; P = .03. Age is linked with inadequate provision of care in myeloma, particularly prognosis and first-line treatment. Compliance to guidelines seems to be related to OS taking into account the main prognostic factors. Future guidelines should stress the point that age and frailty need to be taken into account in myeloma care.

Venous Thrombotic Recurrence After Cerebral Venous Thrombosis: A Long-Term Follow-Up Study.

BACKGROUND AND PURPOSE: After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence. METHODS: Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation. RESULTS: One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence. CONCLUSIONS: In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.

Analysis of factors influencing molecular testing at diagnostic of colorectal cancer.

BACKGROUND: The aim of the study was to evaluate the current rate of molecular testing prescription (KRAS codons 12/13, BRAF and microsatellite instability (MSI)) in newly diagnosed colorectal cancer (CRC) patients and to determine which factors influence testing. METHODS: All incident CRC cases in 2010 were identified in the Poitou-Charentes General Cancer Registry. The exhaustive molecular testing performed was accessed in the French molecular genetics platform. Factors influencing prescription were analyzed using logistic regression. RESULTS: Among the 1269 CRCs included in the study, KRAS, BRAF and MSI testing accounted for 35.1%, 10.5% and 10.9%, respectively. KRAS testing was carried out in 65.5% of metastatic CRCs, and 26.1% of non-metastatic CRCs. Among metastatic CRCs, age (<60 years), site of primary tumour (left colon) and geographical area of treatment were factors related to KRAS testing. BRAF testing was contemporary to KRAS testing for 92.5% of patients. Factors related to MSI testing were age (<60 years), TNM stage (stage IV) and geographical area of treatment. Among CRC patients under 60 years old, only 37.5% had MSI testing. CONCLUSION: These results underscore the need to reduce disparities in CRC molecular testing and highlight the limited application of the French guidelines, especially concerning MSI testing.

Should We Screen for Janus Kinase 2 V617F Mutation in Cerebral Venous Thrombosis?

BACKGROUND: The presence of Janus Kinase 2 (JAK2) V617F mutation represents a major diagnostic criterion for detecting myeloproliferative neoplasms (MPN) and even in the absence of overt MPN, JAK2 V617F mutation is associated with splanchnic vein thrombosis. However, the actual prevalence and diagnostic value of the JAK2 V617F mutation in patients with cerebral venous thrombosis (CVT) are not known. The aims of this study were to assess the prevalence of JAK2 V617F mutation in a large group of consecutive CVT patients, to detect clinical, biological, and radiological features associated with the mutation, and to determine the long-term venous thrombosis recurrence rate in CVT patients with JAK2 mutation but without overt MPN in order to recommend the best preventive treatment. METHODS: This was a prospective study conducted on consecutive patients with a first-ever radiologically confirmed CVT. JAK2 V617F mutation analysis was assessed in all the study subjects. JAK2 V617F-positive patients were followed up to detect new venous thrombotic events. RESULTS: Of the 125 included subjects, 7 were found to have JAK2 V617F mutation (5.6%; 95% CI 2.3-11.2). Older age (p = 0.039) and higher platelet count (p = 0.004) were independently associated with JAK2 V617F positivity in patients without overt MPN. During a mean follow-up period of 59 (SD 46) months, 2 JAK2 V617F-positive patients presented with 4 new venous thromboembolic events. CONCLUSIONS: Screening for the JAK2 V617F mutation in CVT patients seems to be useful even in the absence of overt MPN and/or in the presence of other risk factors for CVT because of its relatively high prevalence and the risk of thrombosis recurrence.

Apical left ventricular myocardial dysfunction is an early feature of cardiac involvement in myotonic dystrophy type 1.

INTRODUCTION: Left ventricular (LV) dysfunction is a major prognostic determinant in myotonic dystrophy type 1 (DM1). Therefore, markers of early-stage LV impairment may be useful. The aim of this study was to evaluate 2D echocardiographic LV strain in a cohort of DM1 patients with preserved left ventricular ejection fraction (LVEF) and to compare the results with matched controls. METHODS: This prospective single-center study included 33 consecutive DM1 patients between February 2014 and February 2015. Mean age was 38.2±12.9 years, and 17 (52%) were males. Exclusion criteria were LVEF <55%, QRS >120 milliseconds, history of atrial fibrillation, and presence of a pacemaker with ventricular pacing. DM1 patients were matched to healthy controls according to sex and age. RESULTS: DM1 patients showed significant impairment of global longitudinal strain (GLS) as compared to controls (-18.0±1.9 vs -19.1±2.4; P=.03), characterized by a marked alteration at the apex (-20.0±3.3 vs -22.7±3.1; P<.001). DM1 patients had also global radial strain impairment (20.0±9.8 vs 27.5±14.9; P=.024) compared to controls while global circumferential strain was not statistically different between groups (P=.94). Intra- and inter-observer analysis showed good reproducibility of GLS. CONCLUSION: Despite preserved LVEF, DM1 patients exhibited significantly altered LV GLS, particularly at the apex, as compared with controls. The detection of impaired myocardial deformation at early stages of the disease might help to screen high-risk patients who need closer follow-up.

Assessment of normal left atrial appendage anatomy and function over gender and ages by dynamic cardiac CT.

OBJECTIVES: The aim of this study was to evaluate variations in anatomy and function according to age and gender using cardiac computed tomography (CT) in a large prospective cohort of healthy patients. BACKGROUND: The left atrial appendage (LAA) is considered the most frequent site of intracardiac thrombus formation. However, variations in normal in vivo anatomy and function according to age and gender remain largely unknown. METHODS: Three-dimensional (3D) cardiac reconstructions of the LAA were performed from CT scans of 193 consecutive patients. Parameters measured included LAA number of lobes, anatomical position of the LAA tip, angulation measured between the proximal and distal portions, minimum (iVolmin) and maximum (iVolmax) volumes indexed to body surface area (BSA), and ejection fraction (LAAEF). Relationship with age was assessed for each parameter. RESULTS: We found that men had longer and wider LAAs. The iVolmin and iVolmax increased by 0.23 and 0.19 ml per decade, respectively, while LAAEF decreased by 2% per decade in both sexes. CONCLUSIONS: Although LAA volumes increase, LAAEF decreases with age in both sexes. KEY POINTS: • Variations in normal left atrial appendage in vivo anatomy and function remain largely unknown. • Cardiac CT is reliable for left atrial appendage volume measurements. • Although LAA volumes increase, LAAEF decreases with age in both sexes.

Predictive factors for complete response of chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma.

OBJECTIVES: To identify clinical and imaging features associated with complete response (CR) to first session of transarterial chemoembolization (TACE) with drug-eluting beads (DEB) in patients with hepatocellular carcinoma. METHODS: In this prospective historical cohort, 172 patients with 315 tumours who received at least one DEB-TACE from 2007 to 2013 were studied. Imaging response was evaluated according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST). Age, gender, aetiology of cirrhosis, Child and BCLC scores, particles size, location in the liver, size of the tumour, presence of a capsule, hypervascularisation on DSA and CT/MRI scans, and blush extinction were analysed. RESULTS: After one session of treatment, CR was observed in 36 % of the 315 tumours treated. Nodule size, location in the liver, and complete blush extinction on DSA was statistically correlated to complete response, whereas capsule aspect on imaging and demographic criteria were not. In multivariate analysis only, location in the liver and nodule size were significant features. CONCLUSIONS: Tumour location in the segments 1 and 4 is a pejorative factor for CR, whereas tumour size <5 cm is a positive predictive factor. These criteria could, therefore, be taken into consideration to improve the selection of patients for DEB-TACE. KEY POINTS: • Literature on predictive factors of complete response after DEB-TACE is under-studied. • Tumour size <5 cm is associated with complete response. • Location in segments 1 or 4 is a pejorative factor for response. • No demographic parameter influences complete response.

Factors associated with orthostatic hypotension in hospitalized elderly patients.

OBJECTIVE: To assess the factors associated with orthostatic hypotension (OH) in hospitalized elderly patients. DESIGN: Prospective observational single center study. SETTING: A French academic center. PARTICIPANTS: One hundred and thirty-one patients without OH symptoms who underwent OH testing. MEASUREMENTS: The OH test was performed when the patient was able to get out of the bed and was no longer receiving parenteral fluids. The blood pressure was measured after a 10-min rest while the patients were sitting and then standing at 1 and 3 min. Demographic data, co-morbidities, current medications and biological parameters were recorded. RESULTS: The mean patient age was 84.3 ± 7 years. The mean CIRS-G score was 10.6 ± 3.8. The OH test was performed 6.3 ± 3.9 days after admission and was positive in 39 (29.8 %) patients (95 % confidence interval (CI) 22, 38) and positive at 1 min in 87.2 % of the cases. Multivariate analysis showed that OH prevalence correlated with diabetes (odds ratio (OR) = 4.23; 95 % CI 1.10, 16.24; P = 0.03), serum 25-hydroxyvitamin D <20 ng/ml (OR = 3.38; 95 % CI 1.36, 8.42; P = 0.008), use of tranquilizers (anxiolytic and hypnotic) (OR = 2.96; 95 % CI 1.18, 7.4; P = 0.02), CIRS-G score (OR = 1.15; 95 % CI 1.01, 1.31; P = 0.03) and lack of diuretics (OR = 0.20; 95 % CI 0.06, 0.63; P = 0.005). CONCLUSION: In older adults, OH is often misdiagnosed because it is asymptomatic. As practitioners may be reluctant to perform the OH test because of time constraints, targeting a subgroup of patients with a higher risk of OH should be worthwhile to prevent further OH complications.

What is the pelvic lymph node normal size? Determination from normal MRI examinations.

PURPOSE: There are few previous reports on maximal pelvic lymph node sizes and no data on normal mesorectal nodes. Therefore, the aim of the study was to estimate the normal size of pelvic lymph nodes and to determine the upper limits of the normal range. MATERIALS AND METHODS: Pelvic magnetic resonance imaging (MRI) examinations were prospectively carried out using a Intera 1.5 T magnet (Philips, the Netherlands), on 36 healthy volunteers (22 females, 14 males, mean age 25 years). A balanced fast field echo (b-FFE) sequence was used with the following parameters: 3-mm-thick contiguous slice, matrix 512 × 512. Short axis diameters of pelvic and inguinal lymph nodes were measured in each anatomic territory (internal iliac, external iliac, common iliac, mesorectum and inguinal). After normalization of the measurements, the influences of age, gender, laterality and territory were evaluated. Upper limits (95th percentile) were then calculated. RESULTS: A total of 1147 lymph nodes were measured. Age, gender and side (right/left) had no significant influence on size. The upper limits of the normal range were, respectively, 5.3, 4.4, 6.3 and 3.9 mm for the external and common iliac, internal iliac, inguinal and mesorectum nodes. CONCLUSION: This work presents maximal normal values for each pelvic area, and the values for mesorectum nodes are reported for the first time. ADVANCES IN KNOWLEDGE: The mesorectum nodes should be considered as abnormal when they are over 4 mm in short diameter. For the other node areas, the upper limits of the normal range were, respectively, 6, 6, 5, 7 mm for the external and common iliac, internal, iliac and inguinal nodes for the short axis.

[Do general practitioners in Geneva (Switzerland) and Poitou-Charentes (France) have different approach to the management of addictions?]. / Comparaison des représentations et comportements des médecins généralistes du Canton de Genève et du Poitou-Charentes.

BACKGROUND: Addiction care is mostly provided by general practitioners (GPs) but the extent of their involvement is variable. Is this related to different training or practice contexts or to awareness campaigns? OBJECTIVE: To study GPs' views and behaviours in relation to addiction patients in different practice and training contexts and different levels of exposure to awareness campaigns. METHODS: Cross-sectional postal survey involving 526 GPs from the canton of Geneva, Switzerland, sensitized by specific addiction care campaigns, compared to 628 GPs from two rural Departments of Poitou-Charentes, France, not exposed to this type of awareness campaign. RESULTS: The response rate was 46% in Switzerland and 41% in France. The 243 responding GPs in Geneva saw as many patients with tobacco, alcohol, cannabis or opiate addiction as the 256 GPs in Poitou-Charentes. They shared similar views concerning their roles in relation to these addictions. Compared to Swiss GPs, a significantly higher number of French GPs provided first-line care for tobacco addiction. In both countries, care for addiction to other substances was mostly provided in collaboration with a specialist (>75% of cases). GPs in Geneva attributed greater importance to screening and recording of substance use. They were also more involved in training and in providing brief advice and expressed interest in the network. CONCLUSION: Awareness campaigns in Geneva could explain these differences. Sensitization of GPs to these issues may contribute to modifying certain professional attitudes, regardless of the context.

A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma. The GOELAMS LCP 99 trial.

Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m(2) (6-hr intravenous [IV]) and 3 mg/m(2) IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m(2) (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m(2) with doses ranging from 12-18 mg/m(2) IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m(2) . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m(2) . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.

Temporal representation of care trajectories of cancer patients using data from a regional information system: an application in breast cancer.

BACKGROUND: Ensuring that all cancer patients have access to the appropriate treatment within an appropriate time is a strategic priority in many countries. There is in particular a need to describe and analyse cancer care trajectories and to produce waiting time indicators. We developed an algorithm for extracting temporally represented care trajectories from coded information collected routinely by the general cancer Registry in Poitou-Charentes region, France. The present work aimed to assess the performance of this algorithm on real-life patient data in the setting of non-metastatic breast cancer, using measures of similarity. METHODS: Care trajectories were modeled as ordered dated events aggregated into states, the granularity of which was defined from standard care guidelines. The algorithm generates each state from the aggregation over a period of tracer events characterised on the basis of diagnoses and medical procedures. The sequences are presented in simple form showing presence and order of the states, and in an extended form that integrates the duration of the states. The similarity of the sequences, which are represented in the form of chains of characters, was calculated using a generalised Levenshtein distance. RESULTS: The evaluation was performed on a sample of 159 female patients whose itineraries were also calculated manually from medical records using the same aggregation rules and dating system as the algorithm. Ninety-eight per cent of the trajectories were correctly reconstructed with respect to the ordering of states. When the duration of states was taken into account, 94% of the trajectories matched reality within three days. Dissimilarities between sequences were mainly due to the absence of certain pathology reports and to coding anomalies in hospitalisation data. CONCLUSIONS: These results show the ability of an integrated regional information system to formalise care trajectories and automatically produce indicators for time-lapse to care instatement, of interest in the planning of care in cancer. The next step will consist in evaluating this approach and extending it to more complex trajectories (metastasis, relapse) and to other cancer localisations.

Smokers with higher positive or negative urgency have lower rates of smoking cessation success 12 months after a quit attempt.

Impulsivity dimensions have been shown to be associated with smoking status and tobacco use disorder severity. However, it is important to determine the specific impulsivity traits associated with smoking relapse. This study aimed at investigating the associations between impulsivity traits and smoking cessation success among adult smokers at 12 months after a quit attempt. Participants were 68 adult smokers enrolled in a 3-month course of simvastatine or placebo associated with behavioral cessation support, with a 9-month follow-up (ADDICSTATINE study). They were classified in 3 groups according to smoking status: abstinent, reduction ≥ 50%baseline or reduction < 50%baseline at 3 and 12 months. Impulsivity traits were assessed using the UPPS-P-scale. At 12 months, abstainers and participants who reduced smoking by 50% or more had significantly lower scores in negative and positive urgency compared to participants who reduced smoking by less than 50% (p = 0.011 and 0.0059). These urgency traits scores at 12 months were significantly and negatively correlated with smoking reduction at 12 months (p = 0.017 and 0.0012). These impulsivity traits were also associated with the smoking cessation success at 3 months. Patients who were abstinent at 3 months had also lower negative and positive urgency (p = 0.017 and 0.0039). Smoking cessation success at 3 and 12 months were not associated with the other impulsivity traits, sensation seeking, lack of premeditation or perseverance. Our findings suggest that positive and negative urgency are associated with smoking cessation success. Proposing better tailored-based-treatment targeting these impulsivity traits in combination with conventional treatment may help improving smoking treatment success.