Skeletal muscle overexpression of sAnk1.5 in transgenic mice does not predispose to type 2 diabetes.

Genome-wide association studies (GWAS) and cis-expression quantitative trait locus (cis-eQTL) analyses indicated an association of the rs508419 single nucleotide polymorphism (SNP) with type 2 diabetes (T2D). rs508419 is localized in the muscle-specific internal promoter (P2) of the ANK1 gene, which drives the expression of the sAnk1.5 isoform. Functional studies showed that the rs508419 C/C variant results in increased transcriptional activity of the P2 promoter, leading to higher levels of sAnk1.5 mRNA and protein in skeletal muscle biopsies of individuals carrying the C/C genotype. To investigate whether sAnk1.5 overexpression in skeletal muscle might predispose to T2D development, we generated transgenic mice (TgsAnk1.5/+) in which the sAnk1.5 coding sequence was selectively overexpressed in skeletal muscle tissue. TgsAnk1.5/+ mice expressed up to 50% as much sAnk1.5 protein as wild-type (WT) muscles, mirroring the difference reported between individuals with the C/C or T/T genotype at rs508419. However, fasting glucose levels, glucose tolerance, insulin levels and insulin response in TgsAnk1.5/+ mice did not differ from those of age-matched WT mice monitored over a 12-month period. Even when fed a high-fat diet, TgsAnk1.5/+ mice only presented increased caloric intake, but glucose disposal, insulin tolerance and weight gain were comparable to those of WT mice fed a similar diet. Altogether, these data indicate that sAnk1.5 overexpression in skeletal muscle does not predispose mice to T2D susceptibility.

Impact of Covid-19 pandemic on neuro-oncology multidisciplinary tumor board in the pre-vaccine era: the Normandy experience.

INTRODUCTION: The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France). METHODS: A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020). RESULTS: Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P=0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P=0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n=79/174) versus 64.5% (n=408/1366), P=0.001. CONCLUSION: The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.

Impact of EGFRA289T/V mutation on relapse pattern in glioblastoma.

BACKGROUND: Molecular factors influence relapse patterns in glioblastoma. The hotspot mutation located at position 289 of the extracellular domain of the epidermal growth factor receptor (EGFRA289mut) is associated with a more infiltrative phenotype. The primary objective of this study was to explore the impact of the EGFRA289 mutation on the pattern of relapse after chemoradiotherapy-based treatment of patients suffering from newly diagnosed glioblastoma. PATIENTS AND METHODS: An ancillary study from a prospective cohort of patients suffering from glioblastoma was conducted. All patients received radiotherapy and concomitant temozolomide. The population was divided into two groups according to EGFRA289 status (mutated versus wild-type). The primary endpoint was the overlap score (varying from 0 to 1) between the initial irradiated tumor volume (Vinit) and the relapse volume (Vr). Secondary endpoints explored the impact of EGFRA289mut on survival. RESULTS: One hundred twenty-eight patients were included and analyzed: 11% had EGFRA289mut glioblastoma (n = 14/128). EGFRA289mut glioblastomas had a relapse pattern that was more marginal than EGFRA289wt glioblastomas: a median overlap score Vinit/Vr of 0.96 was observed in the EGFRA289mut group versus 1 in the EGFRA289wt group (P = 0.05). Half of the population with EGFRA289mut tumor (n = 7/14) had a marginal relapse (i.e. overlap scoreVr/Vinit ≤ 0.95) compared to 23.7% (n = 27/114) in the EGFRA289wt group, P = 0.035. EGFRA289mut did not influence survival. CONCLUSION: We highlighted a link between the EGFRA289 mutation and the relapse pattern in glioblastoma. The independent role of EGFRA289mut and its clinical implication should now be explored in further studies.

Usefulness of circulating tumor DNA from cerebrospinal fluid in recurrent high-grade glioma.

Molecular documentation at relapse of high-grade glioma is an urgent need for patient care. A prospective pilot study was conducted to assess the rate of mutation detection using targeted deep sequencing on circulating tumor DNA from cerebrospinal fluid (CSF) after chemo-radiotherapy based treatment. Fifteen patients were included: 13 patients with glioblastoma, 1 patient with gliosarcoma and 1 patient with anaplastic astrocytoma. At progression, 10/15 patients (67%) had detectable mutations in the CSF. Among them, 5/10 patients harbored at least one common mutation between initial tumor and ctDNA. CSF protein level and cfDNA concentration were higher, although not significant, in the ctDNA positive group versus ctDNA negative group (1.17g/L vs. 0.79g/L). Molecular documentation obtained from ctDNA in CSF at the time of relapse is informative in around two-thirds of the patients.

Suppression of black-hole growth by strong outflows at redshifts 5.8-6.6.

Bright quasars, powered by accretion onto billion-solar-mass black holes, already existed at the epoch of reionization, when the Universe was 0.5-1 billion years old1. How these black holes formed in such a short time is the subject of debate, particularly as they lie above the correlation between black-hole mass and galaxy dynamical mass2,3 in the local Universe. What slowed down black-hole growth, leading towards the symbiotic growth observed in the local Universe, and when this process started, has hitherto not been known, although black-hole feedback is a likely driver4. Here we report optical and near-infrared observations of a sample of quasars at redshifts 5.8 ≲ z ≲ 6.6. About half of the quasar spectra reveal broad, blueshifted absorption line troughs, tracing black-hole-driven winds with extreme outflow velocities, up to 17% of the speed of light. The fraction of quasars with such outflow winds at z ≳ 5.8 is ≈2.4 times higher than at z ≈ 2-4. We infer that outflows at z ≳ 5.8 inject large amounts of energy into the interstellar medium and suppress nuclear gas accretion, slowing down black-hole growth. The outflow phase may then mark the beginning of substantial black-hole feedback. The red optical colours of outflow quasars at z ≳ 5.8 indeed suggest that these systems are dusty and may be caught during an initial quenching phase of obscured accretion5.

[Strategy for the practice of digestive and oncologic surgery in COVID-19 epidemic situation]. / Stratégie pour la pratique de la chirurgie digestive et oncologique en situation d'épidémie de COVID-19.

The COVID-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery - go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer - colon, pancreas, oesogastric, hepatocellular carcinoma - morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and /or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality - oesogastric, hepatic or pancreatic - is most often best deferred.

Strategy for the practice of digestive and oncological surgery during the Covid-19 epidemic.

The Covid-19 pandemic is changing the organization of healthcare and has a direct impact on digestive surgery. Healthcare priorities and circuits are being modified. Emergency surgery is still a priority. Functional surgery is to be deferred. Laparoscopic surgery must follow strict rules so as not to expose healthcare professionals (HCPs) to added risk. The question looms large in cancer surgery-go ahead or defer? There is probably an added risk due to the pandemic that must be balanced against the risk incurred by deferring surgery. For each type of cancer-colon, pancreas, oesogastric, hepatocellular carcinoma-morbidity and mortality rates are stated and compared with the oncological risk incurred by deferring surgery and/or the tumour doubling time. Strategies can be proposed based on this comparison. For colonic cancers T1-2, N0, it is advisable to defer surgery. For advanced colonic lesions, it seems judicious to undertake neoadjuvant chemotherapy and then wait. For rectal cancers T3-4 and/or N+, chemoradiotherapy is indicated, short radiotherapy must be discussed (followed by a waiting period) to reduce time of exposure in the hospital and to prevent infections. Most complex surgery with high morbidity and mortality-oesogastric, hepatic or pancreatic-is most often best deferred.

Impact of locoregional irradiation in patients with upfront metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded. RESULTS: 65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p < 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37). CONCLUSION: LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

FOLFIRINOX as induction treatment in rectal cancer patients with synchronous metastases: Results of the FFCD 1102 phase II trial.

AIM OF THE STUDY: The optimal therapeutic strategy in patients with rectal cancer and synchronous unresectable metastases remains unknown. We evaluated the efficacy of FOLFIRINOX induction therapy in this setting. PATIENTS AND METHODS: Chemotherapy-naïve patients received at least 8 cycles of FOLFIRINOX. The primary end-point was the 4-month disease control (4 m DC) rate. Tumour responses were centrally reviewed and assessed by computed tomography scan for metastases (Response Evaluation Criteria in Solid Tumours criteria) and magnetic resonance imaging for rectal tumorus. With a Simon 2-stage design and a targeted (H1) 4 m DC > 75%, 65 patients were enrolled from July 2012 to February 2015: male, 78%; median age, 61 years; performance status, 0-1, 98%; liver metastases, 92%; ≥2 metastatic sites, 63%. RESULTS: Fifty-six (85%) of the 65 patients received the 8 planned FOLFIRINOX cycles. The primary objective was achieved (4 m DC rate: 94%; 95% confidence interval [CI], 86.3-97.8). Primary tumour symptoms decreased from 72% at baseline to 10% at 4 months. Response rate was 86%, and a >70% primary tumour volume decrease was seen in 63% of patients. Forty-four patients (68%) had at least one grade 3 side-effect; no toxic deaths occurred. Median follow-up was 35.0 months (95% CI, 31.3-43.7). Median progression-free survival and overall survival were 10.9 m (95% CI, 8.8-12.9) and 33.4 m (95% CI, 22.6-38.2), respectively. CONCLUSION: Upfront FOLFIRINOX is feasible and allows good local and distant control. It therefore offers the opportunity to choose the best therapeutic strategy for each patient and to personalise treatment according to the local and distant efficacy results of this induction step. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01674309.

Observations of the missing baryons in the warm-hot intergalactic medium.

It has been known for decades that the observed number of baryons in the local Universe falls about 30-40 per cent short1,2 of the total number of baryons predicted 3 by Big Bang nucleosynthesis, as inferred4,5 from density fluctuations of the cosmic microwave background and seen during the first 2-3 billion years of the Universe in the so-called 'Lyman α forest'6,7 (a dense series of intervening H I Lyman α absorption lines in the optical spectra of background quasars). A theoretical solution to this paradox locates the missing baryons in the hot and tenuous filamentary gas between galaxies, known as the warm-hot intergalactic medium. However, it is difficult to detect them there because the largest by far constituent of this gas-hydrogen-is mostly ionized and therefore almost invisible in far-ultraviolet spectra with typical signal-to-noise ratios8,9. Indeed, despite large observational efforts, only a few marginal claims of detection have been made so far2,10. Here we report observations of two absorbers of highly ionized oxygen (O VII) in the high-signal-to-noise-ratio X-ray spectrum of a quasar at a redshift higher than 0.4. These absorbers show no variability over a two-year timescale and have no associated cold absorption, making the assumption that they originate from the quasar's intrinsic outflow or the host galaxy's interstellar medium implausible. The O VII systems lie in regions characterized by large (four times larger than average 11 ) galaxy overdensities and their number (down to the sensitivity threshold of our data) agrees well with numerical simulation predictions for the long-sought warm-hot intergalactic medium. We conclude that the missing baryons have been found.

Effects in dogs with behavioural disorders of a commercial nutraceutical diet on stress and neuroendocrine parameters.

The well-being of dogs can be affected by changes in human lifestyle, eating habits and increased stressors that lead to behavioural disorders including fear, hyperactivity and anxiety, followed by negative affective moods and poor welfare. This randomised, controlled clinical evaluation involved 69 dogs, 38 males and 31 females, of different breeds, with behavioural disorders related to anxiety and chronic stress. They were fed a control diet or a nutraceutical diet (ND group) for 45 days. Neuroendocrine (serotonin, dopamine, ß-endorphins, noradrenaline and cortisol) and stress (derivatives of reactive oxygen metabolites (dROMs) and biological antioxidant potential (BAP)) parameters related to behavioural disorders were evaluated at the beginning and end of the study period. Results showed a significant increase in serotonin, dopamine and ß-endorphins plasma concentrations (*P<0.05, *P<0.05 and **P<0.01, respectively) and a significant decrease in noradrenaline and cortisol plasma concentrations in the ND group (*P<0.05). dROMs significantly decreased in the ND group (*P<0.05) while BAP was not affected. This study demonstrated for the first time that a specific diet significantly and positively affected neuroendocrine parameters and dROMs. These results open significant perspectives concerning the use of diet and nutraceuticals in the treatment of behavioural disorders.

Port catheter versus peripherally inserted central catheter for postoperative chemotherapy in early breast cancer: a retrospective analysis of 448 patients.

PURPOSE: We aimed to compare the complication rate between port catheters (PC) and peripherally inserted central catheters (PICC) for the administration of postoperative chemotherapy for breast cancer. METHODS: All patients treated from January 2010 to August 2012 at the Centre Henri Becquerel for early breast cancer requiring postoperative chemotherapy were retrospectively screened. The primary endpoint was the occurrence of a major complication related to the central venous catheter. Major complications were defined as any grade 3 event according to CTCAE 4.0, delay in chemotherapy >7 days, change of the device, life-threatening event, event requiring a hospitalization, or a prolongation of hospitalization. RESULTS: A total of 448 patients were included; 290 had a PC and 158 a PICC. Overall, 31 major complications related to the central venous catheter were observed: 13 for patients with a PC (4.5%) and 18 for patients with a PICC (11.4%). In univariate analysis, having a PICC was the only factor significantly associated with a higher risk of major complications (HR = 2.83, p = 0.0027). We observed a trend for a higher risk of major complications for patients older than 60 years or with BMI >25 (p = 0.06). In multivariate analysis, having a PICC was the only predictive factor of major complications (HR = 2.89, p = 0.004). CONCLUSIONS: In univariate and multivariate analysis, having a PICC instead of a PC was the only predictive factor of device-related major complication. If confirmed prospectively by the NCT02095743 ongoing trial, this result might modify the management of adjuvant chemotherapy administration.

[Prognostic factors for metastatic renal cell carcinoma treated with second-line targeted therapies]. / Étude des facteurs pronostiques pour le carcinome rénal métastatique traité par une deuxième ligne de thérapies ciblées.

OBJECTIVE: To assess the prognostic value of clinical and biological features in patients treated with second-line targeted therapies (TT) for a metastatic renal cell carcinoma (mRCC). MATERIAL AND METHODS: A retrospective study was performed including 60 patients treated with second-line TT from 2006 to 2013. Clinical and biological features were collected, including TT-induced toxicities, Heng and MSKCC prognostic scores, and renal function. Overall survival (OS) and progression-free survival (PFS) were assessed using univariate and multivariate analysis. RESULTS: The median age was 61 years [39-81]. MSKCC and Heng scores were significantly prognostic for OS and PFS (P<0.05). Hypo-albuminemia, anemia and brain metastasis were associated with poorer OS and PFS (P<0.05). Severe induced toxicities had a prognostic impact with higher OS (26 months vs 10 months, P=0.003) and PFS (5 months vs 4 months, P=0.047). Renal function impairment at the initiation of the second line was also associated with higher survival (OS=24 months vs 9 months, P=0.035 and PFS=7 months vs 4 months, P=0.043). On multivariate analysis, induced toxicity was found as an independent factor of good prognosis for OS (HR=0.36; P=0.01). CONCLUSION: Our results suggested that renal function impairment and TT-induced toxicities in the second line of treatment for mRCC have a potential prognostic interest as it had previously been reported for the first line of TT. LEVEL OF EVIDENCE: 5.

[Prognostic value of toxicities induced by targeted therapies in patients treated for a metastatic renal cell carcinoma]. / Valeur pronostique de la toxicité induite par les thérapies ciblées dans le carcinome rénal métastatique.

OBJECTIVE: To assess the prognostic value of clinical and biological variables in the era of targeted therapies, especially induced toxicity in patients treated for metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: A retrospective single-center study was performed in patients treated in our center from 2006 to 2012. The clinical and biological variables and toxicity data were retrospectively collected. Survival rates were calculated using the Kaplan-Meier method and compared by the Log-Rank test. Multivariate analysis was also performed using the Cox model. RESULTS: One hundred and two patients were included, with a median follow-up of 20 months. The median overall survival (OS) was 21 months, and 6 months for the progression free survival (PFS). As expected, the variables included in the Mozter prognostic score had a significant impact on OS (P < 0.0001) and PFS (P < 0.0001). However, hypoalbuminemia (P < 0.0001), brain metastasis (P = 0.003) and the absence of nephrectomy (P < 0.0001) were found as poor prognosis factors for OS. In addition, severe toxicity (grade 3-4) was significantly associated with higher OS (P < 0.0001) and PFS (P = 0.0003) and appeared as an independent factor in multivariate analysis for OS (P = 0.02) and PFS (P = 0.01). CONCLUSION: Severe toxicity induced by targeted therapies was found as a prognostic factor increasing significantly the survival. Further studies are needed to assess the real value of this factor in the development of sequential therapies for the treatment of RCC.

Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study.

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. METHODS: Expression of HER2, ß-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. RESULTS: We obtained samples from 63 SBA patients (tumour stages: I-II: 30%; III: 35%; IV: 32%; locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of ß-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9-72.2). For all patients, in univariate analysis, stages I-II (P<0.001), WHO PS 0-1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0-1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0-1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. CONCLUSION: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR.

Definitive chemoradiotherapy in patients with esophageal adenocarcinoma: an alternative to surgery?

BACKGROUND AND OBJECTIVES: Definitive chemoradiotherapy (CRT) is considered curative intent treatment for locally advanced esophageal squamous cell carcinoma. Data concerning the usefulness of definitive CRT in patients with esophageal adenocarcinoma (ADC) are lacking. The aim of the study was to compare the results of definitive CRT versus surgery in patients with an ADC. METHODS: All consecutive patients with a non-metastatic ADC treated between 1994 and 2008 were retrospectively assessed. Patients were divided into two groups: surgery group (±pre-operative treatment) versus definitive CRT group. RESULTS: In surgery and definitive CRT groups, 67 and 79 patients were evaluated, respectively. A complete resection was achieved in 92.5% of patients in surgery group and a clinical complete response was observed in 49.4% of patients in definitive CRT group. Overall survival was 36.2 ± 2.0 months in surgery group versus 16.5 ± 0.8 months in definitive CRT group (P = 0.02). The predictive factors of survival were age (P < 0.01), stage (P = 0.04), WHO performance status (P < 0.01), initial weight loss (P < 0.01), and the treatment group (P < 0.01). CONCLUSIONS: The results of the study do not support definitive CRT as an alternative to surgery in esophageal ADC treatment. Definitive CRT should be reserved for patients with a major operative risk.

Severe clinical toxicities are correlated with survival in patients with advanced renal cell carcinoma treated with sunitinib and sorafenib.

BACKGROUND: In advanced renal cell carcinoma (RCC), sunitinib and sorafenib tyrosine kinase inhibitors (TKI) are associated with several clinical side effects, with no definitive established data concerning their clinical impact. METHODS: From June 2006 to June 2008, main clinical TKI-induced toxicities, including digestive, cardiac, dermatologic and asthenia were retrospectively collected using the NCI-CTC version 3.0 in patients treated with TKI for an RCC. RESULTS: The median overall survival was significantly improved in patients with grade 3-4 clinical toxicities (36 vs 12 months, P=0.009). In multivariate analysis, the Memorial Sloan-Kettering Cancer Center risk groups (good vs intermediate or poor) and clinical toxicities (grade 3-4 vs 1-2) were identified as independent prognostic factors of better survival (P=0.002 and P=0.02, respectively). The Charlson comorbidity index score (>7 vs <7) was identified as independent predictive factor of severe clinical TKI-induced toxicities (P=0.02). CONCLUSION: In this unselected patients of RCC, clinical TKI-related severe toxicities were more frequent in patients with comorbidities and were associated with better survival.

[Chemotherapy and rectal cancer]. / Chimiothérapie du cancer du rectum.

Chemotherapy does not increase the survival time of patients treated for rectal cancer. Chemotherapy given concomitantly to radiotherapy and combined before or after radiation significantly reduces the risk of local recurrence. The sterilization of the tumour (complete pathological response) by chemotherapy is a favourable prognostic factor. New trials on optimisation of pathological complete response rates are based on using drugs effective on metastatic colorectal cancer, given prior to chemoradiotherapy and followed by a resection at least 8 weeks after the end of the radiotherapy. The level of evidence for postoperative chemotherapy is low due to lack of specific study. The indication of postoperative chemotherapy depends on the disease extent after preoperative treatment.

Perfectionism as a mediator between perceived criticism and eating disorders.

OBJECTIVE: In this work we aimed to test the hypothesis that perfectionism plays a third variable role in the psychological process leading from perceived criticism to eating disorders (ED). METHOD: Forty-nine individuals with ED and 49 controls completed the Concern over Mistakes subscale of the Multidimensional Perfectionism Scale, the Perceived Criticism Inventory, and the Drive for Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorders Inventory. Mediational and moderational models were tested. RESULTS: Analyses revealed that perfectionism mediates between perceived criticism and drive for thinness. Results for bulimia and body dissatisfaction were controversial. Moderational models were rejected. DISCUSSION: Results suggest that restrictive dieting is related to a process in which perceived criticism is the initial factor and perfectionism is an intervening mediator.