Risk of anti-TNF therapy on pregnancy, breastfeeding, live vaccines and related information in patients with inflammatory bowel disease: Real-world data from a nationwide study.

BACKGROUND: Anti-TNF are usually maintained during pregnancy in patients with inflammatory bowel disease (IBD) but safety is still a concern for them. AIMS: To provide data on management of anti-TNF agents during pregnancy, safety of live vaccines (BCG-MMR-rotavirus) and breastfeeding in newborns and dedicated information delivered to IBD women. METHODS: We performed an observational study in 25 centers from 2016 to 2018. We administered questionnaires to women with IBD receiving anti-TNF during pregnancy with newborn follow-up ≥ one year. RESULTS: Of 153 patients, 52 % maintained anti-TNF during the third trimester. Anti-TNF was shortly resumed in 79 % (58/73) after delivery. The rate of breastfeeding was 44 % (68/153) without any complication; 38 % of the mothers denied to breastfeed based on physician's advice. 26 % (34/129) of the newborns received live vaccines before 6 months-old (BCG:30 %; MMR:63 %; Rotavirus:8 %) and only 3 complications occurred (local BCGitis=1, fever=2). Information concerning anti-TNF during pregnancy/post-partum was delivered to 92 % of the patients, mainly by a gastroenterologist (97 %) who discussed with the obstetrician or the paediatrician in only 48 % and 25 %. CONCLUSION: In IBD patients, maintaining anti-TNF during pregnancy and breastfeeding is safe. Accidental live vaccines before 6 months did not lead to significant adverse events. The communication about these questions remains to improve.

Triplet chemotherapy with or without bevacizumab as first line treatment for metastatic colorectal cancer: An AGEO multicenter real-world study.

BACKGROUND: Prior trials validated triplet chemotherapy (Tri-CT) with bevacizumab as first line treatment for metastatic colorectal cancer (mCRC) but real-world data are scarce and practices remain heterogeneous. AIMS: To evaluate Tri-CT +/- bevacizumab efficacy and safety, and to identify factors influencing treatment decisions. METHODS: The COLOTRIP retrospective study enrolled mCRC patients treated from 2014 to 2019 in 14 French centers. RESULTS: Of 299 patients (81% PS 0-1, 58% RAS-mutated and 19% BRAF-mutated), 51% received Tri-CT and 49% Tri-CT + bevacizumab. Metastatic disease was classified as resectable (6.5%), potentially resectable (40%), and unresectable (54%). Bevacizumab use was associated with primary tumor location, mutational status and number of metastases. Median overall survival was 33.5 months in the Tri-CT group and 23.9 months in the Tri-CT + bevacizumab group, with median progression-free survival being 14.5 and 11.4 months. After adjusting for initial characteristics, no difference in survival was noted. Around 30% of patients experienced grade ≥3 adverse events. CONCLUSIONS: This study highlights several factors influencing Tri-CT use +/- bevacizumab decision and confirms the real-world good oncological outcomes and tolerability of these regimens in mCRC patients. Our results suggest that Tri-CT alone may by an appropriate option for specific subgroups of patients.

If only they knew! A non-inferiority randomized controlled trial comparing deceptive and open-label placebo in healthy individuals.

BACKGROUND: Placebo use is widespread in clinical practice. However, they are most often administered deceptively rather than openly. It is often suggested that open-label placebos (OLP) are less effective than deceptive placebos (DP). This study aimed to compare the use of DP and OLP treatments to reduce pain in healthy volunteers. METHODS: We conducted a non-inferiority, parallel, randomized, controlled trial, which also included a nested cross-over no-treatment condition. This study was conducted at a university clinic in France. RESULTS: We included 60 subjects and the main result shows that the OLP was not inferior to the DP by a margin of 10 mm. The mean difference between both groups regarding intensity of pain was 0.7 mm with a 95% compatibility interval (95% CI) of ]-∞; 5.4], and 97.5% CI of ]-∞; 6.3]. Secondary outcomes require cautious interpretation of the effect of placebo versus no treatment due to a time-treatment interaction. CONCLUSION: The study indicates that OLP may perform just as well as DP and could provide support for the use of OLP as an ethical alternative to DP when they are to be used in a clinical setting. If only patients knew about the placebo nature of some treatments they are receiving, unnecessary lies could be avoided while maintaining similar placebo effects. SIGNIFICANCE: This study is the first to show non-inferiority of placebos administered honestly, also called OLP, compared to DP in reducing pain. This suggests that OLP could be as effective as their deceptive counterparts while having the ethical advantage of not being required to lie. If deception is not a necessary condition for efficacy, OLP should be preferred over DP.

Artificial intelligence and the future of psychiatry: Qualitative findings from a global physician survey.

BACKGROUND: The potential for machine learning to disrupt the medical profession is the subject of ongoing debate within biomedical informatics. OBJECTIVE: This study aimed to explore psychiatrists' opinions about the potential impact innovations in artificial intelligence and machine learning on psychiatric practice. METHODS: In Spring 2019, we conducted a web-based survey of 791 psychiatrists from 22 countries worldwide. The survey measured opinions about the likelihood future technology would fully replace physicians in performing ten key psychiatric tasks. This study involved qualitative descriptive analysis of written responses ("comments") to three open-ended questions in the survey. RESULTS: Comments were classified into four major categories in relation to the impact of future technology on: (1) patient-psychiatrist interactions; (2) the quality of patient medical care; (3) the profession of psychiatry; and (4) health systems. Overwhelmingly, psychiatrists were skeptical that technology could replace human empathy. Many predicted that 'man and machine' would increasingly collaborate in undertaking clinical decisions, with mixed opinions about the benefits and harms of such an arrangement. Participants were optimistic that technology might improve efficiencies and access to care, and reduce costs. Ethical and regulatory considerations received limited attention. CONCLUSIONS: This study presents timely information on psychiatrists' views about the scope of artificial intelligence and machine learning on psychiatric practice. Psychiatrists expressed divergent views about the value and impact of future technology with worrying omissions about practice guidelines, and ethical and regulatory issues.

[Second- or third-line treatment with erlotinib in EGFR wild-type non-small cell lung cancer: Real-life data]. / Erlotinib en 2e ou 3e ligne pour les cancers bronchiques non à petites cellules sans mutation de l'EGFR : données en vie réelle.

INTRODUCTION: The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. METHODS: The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. RESULTS: Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). CONCLUSION: Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.

Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer.

BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). RESULTS: 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75-91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. CONCLUSION: Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results.

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.

[First treatment strategies in the 2 years following lung cancer diagnosis. ESCAP-2011-CPHG, a real-life study carried out in French general hospitals]. / Stratégies thérapeutiques les 2 premières années après un diagnostic de cancer du poumon. ESCAP-2011-CPHG, étude en situation réelle réalisée dans les hôpitaux généraux français.

INTRODUCTION: The objective of the ESCAP-2011-CPHG cohort study was to perform a real-life analysis of therapeutic strategies used during the first 2years of follow-up after a diagnosis of primary lung cancer. This paper presents the study and its first results in non-small-cell lung cancer (NSCLC). METHODS: Pulmonologists in the respiratory disease departments of 53 general hospitals consecutively included all patients aged 18years and over with lung cancer newly diagnosed in 2010. RESULTS: Of the 3943 patients included, 3418 (mean age: 65.4 years; male: 76%; never smokers: 12%) had NSCLC (adenocarcinoma: 53%; stages 0-II, IIIA, IIIB and IV: 18, 14, 9 and 59%, respectively). Mean follow-up was 13.2 (SD: 10.1) months; mean number of strategies implemented was 2 (SD: 1.3). Overall, 62% of patients had chemotherapy in the first strategy (74% in the second strategy); the rate of chemotherapy alone increased from 6 to 56% with cancer stage. CONCLUSIONS: ESCAP-2011-CPHG opens the way to many possible analyses of the therapeutic strategies currently implemented in French hospitals, comparing strategies, survival or patient characteristics.

Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02).

BACKGROUND: Metastatic colorectal cancer (mCRC) frequently occurs in elderly patients. However, data from a geriatric tailored randomized trial about tolerance to and the efficacy of doublet chemotherapy (CT) with irinotecan in the elderly are lacking. The benefit of first-line CT intensification remains an issue in elderly patients. PATIENTS AND METHODS: Elderly patients (75+) with previously untreated mCRC were randomly assigned in a 2 × 2 factorial design (four arms) to receive 5-FU (5-fluorouracil)-based CT, either alone (FU: LV5FU2 or simplified LV5FU2) or in combination with irinotecan [IRI: LV5FU2-irinotecan or simplified LV5FU2-irinotecan (FOLFIRI)]. The CLASSIC arm was defined as LV5FU2 or LV5FU2-irinotecan and the SIMPLIFIED arm as simplified LV5FU2 or FOLFIRI. The primary end point was progression-free survival (PFS). Secondary end points were overall survival (OS), safety and objective response rate (ORR). RESULTS: From June 2003 to May 2010, 71 patients were randomly assigned to LV5FU2, 71 to simplified LV5FU2, 70 to LV5FU2-irinotecan and 70 to FOLFIRI. The median age was 80 years (range 75-92 years). No significant difference was observed for the median PFS: FU 5.2 months versus IRI 7.3 months, hazard ratio (HR) = 0.84 (0.66-1.07), P = 0.15 and CLASSIC 6.5 months versus SIMPLIFIED 6.0 months, HR = 0.85 (0.67-1.09), P = 0.19. The ORR was superior in IRI (P = 0.0003): FU 21.1% versus IRI 41.7% and in CLASSIC (P = 0.04): CLASSIC 37.1% versus SIMPLIFIED 25.6%. Median OS was 14.2 months in FU versus 13.3 months in IRI, HR = 0.96 (0.75-1.24) and 15.2 months in CLASSIC versus 11.4 months in SIMPLIFIED, HR = 0.71 (0.55-0.92). More patients presented grade 3-4 toxicities in IRI (52.2% versus 76.3%). CONCLUSION: In this elderly population, adding irinotecan to an infusional 5-FU-based CT did not significantly increase either PFS or OS. Classic LV5FU2 was associated with an improved OS compared with simplified LV5FU2. CLINICALTRIALSGOV: NCT00303771.

Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort.

BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.

[Ten-year evolution in non-small-cell lung cancer according to sex. Results of the KBP-2010-CPHG study by the College of General Hospital Respiratory Physicians]. / Évolution en 10ans du cancer bronchique non à petites cellules en fonction du sexe. Résultats de l'étude KBP-2010-CPHG du Collège des pneumologues des hôpitaux généraux.

INTRODUCTION: Comparison by sex and presenting features between 2000 and 2010 of the characteristics of new cases of non-small-cell lung cancer (NSCLC). METHODS: Observational KBP-2010-CPHG study similar to KBP-2000-CPHG. Both studies were promoted by the French College of General Hospital Respiratory Physicians (CPHG). KBP-2010-CPHG collected data for 6083 NSCLC diagnosed between January 1st and December 31st, 2010, and followed in the respiratory departments of 119 French general hospitals. RESULTS: In 2010, 24.4 % of the patients were women (16 % in 2000, p<0.0001). Compared to men, women were more commonly non-smokers (34.2 vs 4.7 %) or lighter consumers (37.2 vs 43.7 pack per years) (p<0.0001). Their tumours (mostly adenocarcinoma: 64.6 vs 48.7 %, p<0.0001) were more frequently diagnosed at stage IV (62.4 vs 56.9 %, p=0.0008). EGFR mutation research was more frequently performed (48.5 vs 31.0 %, p<0.0001) and positive (20.6 vs 5.2 %, p<0.0001) in women than men. Their treatment more frequently included targeted therapy (13.4 vs 5.7 %, p<0.0001). Compared to 2000, the percentage of non-smokers increased in men (4.7 vs 2.5 %, p<0.0001) while remaining stable in women (36.1 vs 34.2 %, p=0.32). The percentage of adenocarcinomas increased, particularly in men (48.7 vs 31.5 %, p<0.0001). CONCLUSIONS: The percentage of women with NSCLC has increased in 10years in France. In 2010, the main gender differences persist, but have decreased with the increasing proportion of non-smokers and adenocarcinomas in men. Various hypotheses to explain these changes are discussed.

Defective immunogenic cell death of HMGB1-deficient tumors: compensatory therapy with TLR4 agonists.

Immunogenic cell death induced by anticancer chemotherapy is characterized by a series of molecular hallmarks that include the exodus of high-mobility group box 1 protein (HMGB1) from dying cells. HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and engages Toll-like receptor4 (TLR4) on dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. Here, we show that transplantable tumors exhibiting weak expression of nuclear HMGB1 respond to chemotherapy more effectively if the treatment is combined with the local or systemic administration of a highly purified and physiochemically defined and standardized lipopolysaccharide solution, which acts as a high-potency and exclusive TLR4 agonist, called Dendrophilin (DEN). The synergistic antitumor effects mediated by the combination of chemotherapy and immunotherapy relied upon the presence of the MyD88 (myeloid differentiation primary response gene) adapter of TLR4 (but not that of the TIR-domain-containing adapter-inducing interferon-ß adapter), in line with the well-characterized action of DEN on the MyD88 signaling pathway. DEN and anthracyclines synergized to induce intratumoral accumulation of interferon-γ-producing CD4(+) and CD8(+) T lymphocytes. Moreover, DEN could restore the immunogenicity of dying tumor cells from which HMGB1 had been depleted by RNA interference. These findings underscore the potential clinical utility of combination regimens involving immunogenic chemotherapy and certain TLR4 agonists in advanced HMGB1-deficient cancers.

Contribution of humoral immune responses to the antitumor effects mediated by anthracyclines.

Immunogenic cell death induced by cytotoxic compounds contributes to the success of selected chemotherapies by eliciting a protective anticancer immune response, which is mediated by CD4(+) and CD8(+) T cells producing interferon-γ. In many instances, cancer progression is associated with high titers of tumor-specific antibodies, which become detectable in the serum, but whose functional relevance is elusive. Here, we explored the role of humoral immune responses in the anticancer efficacy of anthracyclines. Chemotherapy reduced the number of tumor-infiltrating B cells, and failed to promote humoral responses against immunodominant tumor antigens. Although anthracycline-based anticancer chemotherapies failed in T cell-deficient mice, they successfully reduced the growth of cancers developing in mice lacking B lymphocytes (due to the injection of a B-cell-depleting anti-CD20 antibody), immunoglobulins (Igs) or Ig receptors (Fc receptor) due to genetic manipulations. These results suggest that the humoral arm of antitumor immunity is dispensable for the immune-dependent therapeutic effect of anthracyclines against mouse sarcoma. In addition, we show here that the titers of IgA and IgG antibodies directed against an autoantigen appearing at the cell surface of tumor cells post chemotherapy (calreticulin, CRT) did not significantly increase in patients treated with anthracyclines, and that anti-CRT antibodies had no prognostic or predictive significance. Collectively, our data indicate that humoral anticancer immune responses differ from cellular responses in, thus far, that they do not contribute to the success of anthracycline-mediated anticancer therapies in human breast cancers and mouse sarcomas.

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.

Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II-III colorectal cancer.

BACKGROUND: The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II-III CRC patients. METHODS: We constructed a tissue microarray from 196 consecutive patients with stage II-III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models. RESULTS: Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs -, ≤2 cells per spot) and CD68 (+, >0 vs -, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57-), or high (CD68-/CD57-) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3-5.8) and 9.0 (3.2-25.4) for RFS, and 2.5 (1.2-5.1) and 10.6 (3.8-29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71-91), 65% (54-74), and 12% (2-47), respectively, for RFS, and 91% (80-96), 76% (66-84), and 25% (7-59), respectively, for OS. CONCLUSION: Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II-III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.

Chemical characteristics and antimicrobial effects of some Eucalyptus kinos.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus kinos are tannin-rich, mostly red-coloured wood exudates. They have played an important role in the traditional medicines of Australian Aboriginal people and were also a valued source of antibacterial and astringent agents for early European settlers. MATERIALS AND METHODS: Nineteen different Eucalyptus kinos were collected and analysed for their total phenolics and total tannin content as well as their relative amounts of hydrolysable and condensed tannins. They were also classified in accordance with Maiden's traditional kino categories. Well plate diffusion assays using three Gram positive and two Gram negative bacteria and a yeast species were carried out to assess antimicrobial properties. RESULTS: The investigated kino samples differ strongly in their total phenolics and overall tannin as well as their relative hydrolysable and condensed tannin contents. All but one could be assigned to one of the traditional Maiden kino classes. The samples, in particular those collected from Corymbia maculata and Eucalyptus ficifolia, demonstrated a strong antibacterial activity towards Gram positive bacteria but were inactive against the Gram negative strains and the yeast. No obvious correlation seems to exist between a particular Maiden class and antibacterial activity but there is a positive correlation between total phenolics/tannin content and antibacterial effect although two of the investigated kinos (Eucalyptus flocktoniae and Eucalyptus sargentii) deviated from this trend. The relative amounts of hydrolysable and condensed tannins in a kino sample do not seem to determine the antibacterial effect. CONCLUSION: Eucalpytus kinos present an interesting class of natural products which should be investigated further, not only to contribute to the growing field of tannin chemistry but to also learn more about the individual role played by the various hydrolysable and condensed tannins that determine a kino's antibacterial activity and to contribute to a better understanding of the use of some of these kinos in traditional systems of medicine. In particular samples like Eucalyptus flocktoniae kino, which recorded a higher antibacterial activity than predicted based on total tannin content, warrant more detailed chemical and antimicrobial analyses.

Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.

Although malnutrition is known to be frequent in cancer patients, it has not been described in a selected population of patients with gastrointestinal malignancies under chemotherapy only. Physician judgment about malnutrition and risk factors for malnutrition were also evaluated. All consecutive in- and outpatients of 11 centers were prospectively enrolled in a cross-sectional 14-day period study and classified according to the French health recommendations [Haute Autorité de Santé (HAS)]. Among 313 patients enrolled in 11 centers (mean age = 63 yr; range = 21-93; 67% male) mainly with colorectal (58%), pancreatic (15%), gastric (11%), and hepatobiliary (10%) primary tumors, the prevalence of malnutrition was 52%. Moderate and severe malnutrition was present in 27% and 25% of cases, respectively. Physicians considered it in 36% and 6% of cases, respectively, thereby misclassifying 134 patients (43%). The agreement between the HAS definition and the physicians' judgment was very low (κ = 0.30). Most of the patients who were identified as severely malnourished received no nutritional support. Performance status and pancreatic and gastric cancers were independently associated with malnutrition. Malnutrition levels are high, around 50%, unequally distributed according to the primitive tumor. It is still underestimated by physicians. Weight loss remains a clinically relevant, simple, and reliable marker of malnutrition.

Operating experiences with a molten carbonate fuel cell at Stuttgart-Möhringen wastewater treatment plant.

Fuel cells on wastewater treatment plants are a relatively new technology to convert biogas from anaerobic digestion into thermal and electrical energy. Since the end of 2007, a type of MCFC fuel cell (>250 kW(el), 180 kW(th)) has been installed at Stuttgart-Möhringen wastewater treatment plant. The goals of this research project are to raise the power self-sufficiency in Stuttgart-Möhringen, to further optimise high temperature fuel cells using biogas and to gain practical experience. After approximately 9,000 h of operation, a mean electrical 'gross'-efficiency of 44% was achieved. To fully exploit this high electrical efficiency, it is essential to keep the energy consumption of peripheral devices (gas pressure unit, gas cleaning unit, etc.) of the fuel cell as low as possible.

[A phase II study of weekly cisplatine plus oral vinorelbine with concomittant radiotherapy in non-dependent elderly patients with localized inoperable non small cell lung carcinoma (Essai GFPC 08-06, Raccosa)]. / Radio-chimiothérapie concomitante chez le sujet âgé indépendant (Essai GFPC 0806 RACCOSA).

UNLABELLED: A phase II study of weekly cisplatine plus oral vinorelbine with concomittant radiotherapy in non-dependent elderly patients with localized inoperable non small cell lung carcinoma (Essai GFPC 08-06, Raccosa). BACKGROUND: Non small cell lung cancer (NSCLC) in elderly patients is an important problem because of the increasing incidence of NSCLC and the aging of the population. Elderly patients constitute a heterogeneous population including a significant group of relatively fit patients who ought to benefit from the conventional treatment. The standard treatment for a locally advanced NSCLC (inoperable IIIA and IIIB) is concomitant radiochemotherapy, however studies evaluating this treatment to the old subject are few. METHODS: This phase II study aims to evaluate tolerance of concomitant radiochemotherapy in fit elderly patients (more than 70 years old) with locally advanced NSCLC (inoperable IIIAN2 or IIIB). The treatment is oral vinorelbine (30 mg/m(2) per week) and intravenous cisplatine (30 mg/m(2) per week) during 6 weeks in conjunction with radiotherapy (66 Gy, 33 fraction, six and a half weeks). The main criterion of evaluation is acute toxicity. Late toxicity, quality of life, global response, time to progression and overall survival will also be estimated. With a Simon's optimal plan in two steps, the total number of patients to be included is 59 with an intermediate analysis after the inclusion of 19 patients. EXPECTED RESULTS: Our study aims to demonstrate that fit elderly patients can benefit from concomitant radiochemotherapy. It will permit an improvement in the care available for fit elderly patients with locally advanced NSCLC by allowing them to benefit from the reference treatment.