Nouveautés dans la stratégie thérapeutique de la diverticulite sigmoïdienne [Current treatment strategies for sigmoid diverticulitis]

Treatment of colonic diverticular disease has evolved over the past years. Most episodes are simple and can be successfully treated with antibiotics alone. For complicated diverticulitis, a strong trend is developing towards less invasive therapies including interventional radiology and laparoscopic lavage in an effort to avoid the morbidity and discomfort of a diverting colostomy. Based on a better understanding of the natural history of the disease, the indication to prophylactic colectomy after a few episodes of simple diverticulitis has been seriously challenged. For those patients who need a colectomy, single port laparoscopy, NOTES and transanal specimen extraction are being proposed. However larger studies are needed to confirm the hypothetical advantages of these evolving techniques.

Tissue distribution of the Ankara strain of vaccinia virus (MVA) after mucosal or systemic administration.

MVA is a candidate vector for vaccination against pathogens and tumors. Little is known about its behaviour in mucosal tissues. We have investigated the fate and biosafety of MVA, when inoculated by different routes in C57BL/6 mice. Intranasal inoculation targeted the virus to the nasal associated lymphoid tissue and the lungs, whereas systemic inoculation led to distribution of MVA in almost all lymphoid organs, lungs and ovaries. Intravaginal, intrarectal and intragastric inoculations failed to induce efficient infection. After 48 h no virus was detectable any more in the organs analyzed. Upon intranasal inoculation, no inflammatory reactions were detected in the central nervous system as well as the upper and lower airways. These results show the tropism of MVA and indicate that high doses of recombinant MVA are safe when nasally administered, a vaccination route known to elicit strong cellular and humoral immune responses in the female genital tract.

Laparoscopie abdominale: possibilités et limites [Abdominal laparoscopy: an update]

Laparoscopic surgery has become a standard approach for many interventions, including oncologic surgery. Laparoscopic instruments have been developed to allow advanced surgical procedure. Imaging and computer assistance in virtual reality or robotic procedure will certainly improve access to this surgery.

Maternal age-specific risk of non-chromosomal anomalies.

OBJECTIVES: To determine the excess risk of non-chromosomal congenital anomaly (NCA) among teenage mothers and older mothers. DESIGN AND SETTING: Population-based prevalence study using data from EUROCAT congenital anomaly registers in 23 regions of Europe in 15 countries, covering a total of 1.75 million births from 2000 to 2004. PARTICIPANTS: A total of 38,958 cases of NCA that were live births, fetal deaths with gestational age > or = 20 weeks or terminations of pregnancy following prenatal diagnosis of a congenital anomaly. MAIN OUTCOME MEASURES: Prevalence of NCA according to maternal age, and relative risk (RR) of NCA and 84 standard NCA subgroups compared with mothers aged 25-29. RESULTS: The crude prevalence of all NCA was 26.5 per 1000 births in teenage mothers (<20 years), 23.8 for mothers 20-24 years, 22.5 for mothers 25-29 years, 21.5 for mothers 30-34 years, 21.4 for mothers 35-39 years and 22.6 for mothers 40-44 years. The RR adjusted for country for teenage mothers was 1.11 (95% CI 1.06-1.17); 0.99 (95% CI 0.96-1.02) for mothers 35-39; and 1.01 (95% CI 0.95-1.07) for mothers 40-44. The pattern of maternal age-related risk varied significantly between countries: France, Ireland and Portugal had higher RR for teenage mothers, Germany and Poland had higher RR for older mothers. The maternal age-specific RR varied for different NCAs. Teenage mothers were at a significantly greater risk (P < 0.01) of gastroschisis, maternal infection syndromes, tricuspid atresia, anencephalus, nervous system and digestive system anomalies while older mothers were at a significantly greater risk (P < 0.01) of fetal alcohol syndrome, encephalocele, oesophageal atresia and thanatophoric dwarfism. CONCLUSIONS: Clinical and public health interventions are needed to reduce environmental risk factors for NCA, giving special attention to young mothers among whom some risk factors are more prevalent. Reassurance can be given to older mothers that their age in itself does not confer extra risk for NCA.

Nutrition préopératoire en chirurgie viscérale: recommandations et réalité [Preoperative nutrition in abdominal surgery: recommendations and reality].

Malnutrition concerns up to 50% at in-hospital admission. Its diagnosis and treatment are fundamental parts of the surgical approach because nutritional status directly influences the clinical outcome. The Nutritional Risk Score (NRS-2002) represents the recommended screening tool by the European Society of Parenteral and Enteral Nutrition (ESPEN). Patients with a score > or = 3 and aged > 70 years old, should receive a nutritional support during 7-14 day before surgery. Depending on patient's clinical conditions, the enteral route of administration should be preferred. Despite strong evidence in favor of nutritional supplementation, much effort must be done to implement these supportive strategies in the everyday clinical practice.

Distribution of neuropeptide Y Y1 receptors in rodent peripheral tissues.

Using a sensitive immunohistochemical technique, the localization of neuropeptide Y (NPY) Y1-receptor (Y1R)-like immunoreactivity (LI) was studied in various peripheral tissues of rat. Wild-type (WT) and Y1R-knockout (KO) mice were also analyzed. Y1R-LI was found in small arteries and arterioles in many tissues, with particularly high levels in the thyroid and parathyroid glands. In the thyroid gland, Y1R-LI was seen in blood vessel walls lacking alpha-smooth muscle actin, i.e., perhaps in endothelial cells of capillaries. Larger arteries lacked detectable Y1R-LI. A distinct Y1R-immunoreactive (IR) reticulum was seen in the WT mouse spleen, but not in Y1R-KO mouse or rat. In the gastrointestinal tract, Y1R-positive neurons were observed in the myenteric plexus, and a few enteroendocrine cells were Y1R-IR. Some cells in islets of Langerhans in the pancreas were Y1R-positive, and double immunostaining showed coexistence with somatostatin in D-cells. In the urogenital tract, Y1R-LI was observed in the collecting tubule cells of the renal papillae and in some epithelial cells of the seminal vesicle. Some chromaffin cells of adrenal medulla were positive for Y1R. The problem of the specificity of the Y1R-LI is evaluated using adsorption tests as well as comparisons among rat, WT mouse, and mouse with deleted Y1R. Our findings support many earlier studies based on other methodologies, showing that Y1Rs on smooth muscle cells of blood vessels mediate NPY-induced vasoconstriction in various organs. In addition, Y1Rs in other cells in parenchymal tissues of several organs suggest nonvascular effects of NPY via the Y1R.

Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

Laparoscopy in the era of enhanced recovery.

Laparoscopy is one of the cornerstones in the surgical revolution and transformed outcome and recovery for various surgical procedures. Even if these changes were widely accepted for basic interventions, like appendectomies and cholecystectomies, laparoscopy still remains challenged for more advanced operations in many aspects. Despite these discussion, there is an overwhelming acceptance in the surgical community that laparoscopy did transform the recovery for several abdominal procedures. The importance of improved peri-operative patient management and its influence on outcome started to become a focus of attention 20 years ago and is now increasingly spreading, as shown by the incoming volume of data on this topic. The enhanced recovery after surgery (ERAS) concept incorporates simple measures of general management, and requires multidisciplinary collaboration from hospital staff as well as the patient and the relatives. Several studies have demonstrated a significant decrease in postoperative complication rate, length of hospital stay and reduced overall cost. The key elements of success are fluid restriction, a functioning epidural and preoperative carbohydrate intake. With the expansion of laparoscopic techniques, ERAS increasingly incorporates laparoscopic patients, especially in colorectal surgery. However, the precise impact of laparoscopy on ERAS is still not clearly defined. Increasing evidence suggests that laparoscopy itself is an additional ERAS item that should be considered as routine where feasible in order to obtain the best surgical outcomes.

Fistulizing Crohn's disease.

Fistulas are common in Crohn's disease. A population-based study has shown a cumulative risk of 33% after 10 years and 50% after 20 years. Perianal fistulas were the most common (54%). Medical therapy is the main option for perianal fistula once abscesses, if present, have been drained, and should include antibiotics (both ciprofloxacin and metronidazole) and immunomodulators. Infliximab should be reserved for refractory patients. Surgery is often necessary for internal fistulas.

Eosinophilic oesophagitis: relationship of quality of life with clinical, endoscopic and histological activity.

BACKGROUND: Knowledge about determinants of quality of life (QoL) in eosinophilic oesophagitis (EoO) patients helps to identify patients at risk of experiencing poor QoL and to tailor therapeutic interventions accordingly. AIM: To evaluate the impact of symptom severity, endoscopic and histological activity on EoE-specific QoL in adult EoE patients. METHODS: Ninety-eight adult EoE patients were prospectively included (64% male, median age 39 years). Patients completed two validated instruments to assess EoE-specific QoL (EoO-QoL-A) and symptom severity (adult EoE activity index patient-reported outcome) and then underwent esophagogastroduodenoscopy with biopsy sampling. Physicians reported standardised information on EoE-associated endoscopic and histological alterations. The Spearman's rank correlation coefficient was calculated to determine the relationship between QoL and symptom severity. Linear regression and analysis of variance was used to quantify the extent to which variations in severity of EoE symptoms, endoscopic and histological findings explain variations in QoL. RESULTS: Quality of life strongly correlated with symptom severity (r = 0.610, P < 0.001). While the variation in severity of symptoms, endoscopic and histological findings alone explained 38%, 35% and 22% of the variability in EoE-related QoL, respectively, these together explained 60% of variation. Symptom severity explained 18-35% of the variation in each of the five QoL subscale scores. CONCLUSIONS: Eosinophilic oesophagitis symptom severity and biological disease activity determine QoL in adult patients with eosinophilic oesophagitis. Therefore, reduction in both eosinophilic oesophagitis symptoms as well as biological disease activity is essential for improvement of QoL in adult patients. Clinicaltrials.gov number, NCT00939263.

Traitements chirurgicaux des maladies fonctionnelles oesogastriques [Surgical treatment of gastroesophageal diseases].

Les pathologies fonctionnelles oesogastriques regroupent plusieurs maladies touchant la fonction digestive haute : la maladie de reflux, les hernies hiatales, l'oesophage court et l'achalasie. Leur mode de présentation est parfois similaire, mais leur traitement diffère sur de nombreux points. L'approche initiale passe souvent par une modification de l'hygiène de vie et une prise en charge médicale. Mais une prise en charge chirurgicale est parfois nécessaire. Une sélection très stricte des patients permet de garantir un bon résultat à long terme, tout en limitant le risque de complications. Elle repose sur un bilan fonctionnel précis et une prise en charge dans le cadre de discussions multidisciplinaires. Cette revue fait un point actuel sur la prise en charge générale, les bilans nécessaires et les traitements chirurgicaux disponibles. Gastroesophageal functional diseases comprise several pathologies impending upper gastrointestinal function: reflux disease, hiatal hernias, short esophagus and achalasia. Their presentation may be similar, but their treatment differs on many points. The initial approach consists of lifestyle changes and medical management. However, surgical treatment is sometimes necessary. Strict patient selection ensures good long-term results, while limiting the risk of complications. This selection is based on precise functional assessment and management in the context of multidisciplinary discussions. This article aims to discuss current aspects on general management, functional investigations and surgical treatments available.

Peroxisome proliferator-activated receptor gamma and regulations by the ubiquitin-proteasome system in pancreatic cancer.

Pancreatic cancer is one of the most lethal forms of human cancer. Although progress in oncology has improved outcomes in many forms of cancer, little progress has been made in pancreatic carcinoma and the prognosis of this malignancy remains grim. Several molecular abnormalities often present in pancreatic cancer have been defined and include mutations in K-ras, p53, p16, and DPC4 genes. Nuclear receptor Peroxisome Proliferator-Activated Receptor gamma (PPARγ) has a role in many carcinomas and has been found to be overexpressed in pancreatic cancer. It plays generally a tumor suppressor role antagonizing proteins promoting carcinogenesis such as NF-κB and TGFβ. Regulation of pathways involved in pancreatic carcinogenesis is effectuated by the Ubiquitin Proteasome System (UPS). This paper will examine PPARγ in pancreatic cancer, the regulation of this nuclear receptor by the UPS, and their relationship to other pathways important in pancreatic carcinogenesis.

The ubiquitin-proteasome system in prostate cancer and its transition to castration resistance.

Prostate cancer is the most common carcinoma in the male population. In its initial stage, the disease is androgen-dependent and responds therapeutically to androgen deprivation treatment but it usually progresses after a few years to an androgen-independent phase that is refractory to hormonal manipulations. The proteasome is a multi-unit protease system that regulates the abundance and function of a significant number of cell proteins, and its inhibition results in cancer cell growth inhibition and apoptosis and is already exploited in the clinic with the use of proteasome inhibitor bortezomib in multiple myeloma. In order to be recognized by the proteasome, a target protein needs to be linked to a chain of the small protein ubiquitin. In this paper, we review the role of ubiquitin-proteasome system (UPS) in androgen receptor-dependent transcription as well as in the castration resistant stage of the disease, and we discuss therapeutic opportunities that UPS inhibition offers in prostate cancer.

The role of chemokines in cancer immune surveillance by the adaptive immune system.

Chemokines are key molecules involved in the migration and homeostasis of immune cells. However, also tumor cells use chemokine signals for different processes such as tumor progression and metastasis. It is thus unclear whether chemokines, through their immunostimulatory roles, contribute to the repression of tumor cells by tumor immunosurveillance or whether chemokines act primarily as growth factors and chemoattractants for primary and metastatizing tumors, respectively. Research of recent years, using gene knockout mice, recombinant chemokines, and agents able to block chemokine actions, has provided further insight into the diverse functions of chemokines. Here, we review the current knowledge on the complex actions of chemokines at the interface of the immune system and the tumor.

Oral cancer treatments and adherence: medication event monitoring system assessment for capecitabine

Background: Oncological treatments are traditionally administered via intravenous injection by qualified personnel. Oral formulas which are developing rapidly are preferred by patients and facilitate administration however they may increase non-adherence. In this study 4 common oral chemotherapeutics are given to 50 patients, who are still in the process of inclusion, divided into 4 groups. The aim is to evaluate adherence and offer these patients interdisciplinary support with the joint help of doctors and pharmacists. We present here the results for capecitabine. Materials and Methods: The final goal is to evaluate adhesion in 50 patients split into 4 groups according to oral treatments (letrozole/exemestane, imatinib/sunitinib, capecitabine and temozolomide) using persistence and quality of execution as parameters. These parameters are evaluated using a medication event monitoring system (MEMS®) in addition to routine oncological visits and semi-structured interviews. Patients were monitored for the entire duration of treatment up to a maximum of 1 year. Patient satisfaction was assessed at the end of the monitoring period using a standardized questionary. Results: Capecitabine group included 2 women and 8 men with a median age of 55 years (range: 36−77 years) monitored for an average duration of 100 days (range: 5-210 days). Persistence was 98% and quality of execution 95%. 5 patients underwent cyclic treatment (2 out of 3 weeks) and 5 patients continuous treatment. Toxicities higher than grade 1 were grade 2−3 hand-foot syndrome in 1 patient and grade 3 acute coronary syndrome in 1 patient both without impact on adherence. Patients were satisfied with the interviews undergone during the study (57% useful, 28% very useful, 15% useless) and successfully integrated the MEMS® in their daily lives (57% very easily, 43% easily) according to the results obtained by questionary at the end of the monitoring period. Conclusion: Persistence and quality of execution observed in our Capecitabine group of patients were excellent and better than expected compared to previously published studies. The interdisciplinary approach allowed us to better identify and help patients with toxicities to maintain adherence. Overall patients were satisfied with the global interdisciplinary follow-up. With longer follow up better evaluation of our method and its impact will be possible. Interpretation of the results of patients in the other groups of this ongoing trial will provide us information for a more detailed analysis.