Transvaginal specimen extraction in colorectal surgery: current state of the art.

Aim  Background The expected benefit of transvaginal specimen extraction is reduced incision-related morbidity. Objectives A systematic review of transvaginal specimen extraction in colorectal surgery was carried out to assess this expectation. Method  Search strategy The following keywords, in various combinations, were searched: NOSE (natural orifices specimen extraction), colorectal, colon surgery, transvaginal, right hemicolectomy, left hemicolectomy, low anterior resection, sigmoidectomy, ileocaecal resection, proctocolectomy, colon cancer, sigmoid diverticulitis and inflammatory bowel diseases. Selection criteria Selection criteria included large bowel resection with transvaginal specimen extraction, laparoscopic approach, human studies and English language. Exclusion criteria were experimental studies and laparotomic approach or local excision. All articles published up to February 2011 were included. Results  Twenty-three articles (including a total of 130 patients) fulfilled the search criteria. The primary diagnosis was colorectal cancer in 51% (67) of patients, endometriosis in 46% (60) of patients and other conditions in the remaining patients. A concurrent gynaecological procedure was performed in 17% (22) of patients. One case of conversion to laparotomy was reported. In two patients, transvaginal extraction failed. In left- and right-sided resections, the rate of severe complications was 3.7% and 2%, respectively. Two significant complications, one of pelvic seroma and one of rectovaginal fistula, were likely to have been related to transvaginal extraction. The degree of follow up was specified in only one study. Harvested nodes and negative margins were adequate and reported in 70% of oncological cases. Conclusion  Vaginal extraction of a colorectal surgery specimen shows potential benefit, particularly when associated with a gynaecological procedure. Data from prospective randomized trials are needed to support the routine use of this technique.

Performance of a chromatographic procedure used in the certification of reference material for polycyclic aromatic hydrocarbons in sewage sludge

Semi-automatic capillary gas chromatographic method with classical flame ionization detection, which satisfies the conditions for required performance and gave acceptable results within the framework of an interlaboratory certification programme for PAHs in sewage sludge, is described. The interesting feature of the procedure is that it incorporates automatic operations such as sample fractionation by semi-preparative HPLC, fraction collection at signal level recognition and evaporation under nitrogen flow. Multiple injections in the GC capillary column are performed in the on-column mode via an autosampler with temperature-programmable injector. Automatic data acquisition and chromatogram treatment are made via computer software. This partially automatic procedure releases personnel from tedious and time-consuming tasks and its robust character was validated through the certification of reference material for PAHs in sewage sludge, demonstrating its reliable performance.

Current state of vaccine therapies in non-small-cell lung cancer.

A large variety of cancer vaccines have undergone extensive testing in early-phase clinical trials. A limited number have also been tested in randomized phase II clinical trials. Encouraging trends toward increased survival in the vaccine arms have been recently observed for 2 vaccine candidates in patients with non-small-cell lung cancer. These have provided the impetus for the initiation of phase III trials in large groups of patients with lung cancer. These vaccines target 2 antigens widely expressed in lung carcinomas: melanoma-associated antigen 3, a cancer testis antigen; and mucin 1, an antigen overexpressed in a largely deglycosylated form in advanced tumors. Therapeutic cancer vaccines aim at inducing strong CD8 and CD4 T-cell responses. The majority of vaccines recently tested in phase I clinical trials show efficacy in terms of induction of specific tumor antigen immunity. However, clinical efficacy remains to be determined but appears limited. Efforts are thus aimed at understanding the basis for this apparent lack of effect on tumors. Two major factors are involved. On one hand, current vaccines are suboptimal. Strong adjuvant agents and appropriate tumor antigens are needed. Moreover, dose, route, and schedule also need optimization. On the other hand, it is now clear that large tumors often present a tolerogenic microenvironment that hampers effective antitumor immunity. The partial understanding of the molecular pathways leading to functional inactivation of T cells at tumor sites has provided new targets for intervention. In this regard, blockade of cytotoxic T-lymphocyte antigen-4 and programmed death-1 with humanized monoclonal antibodies has reached the clinical testing stage. In the future, more potent cancer vaccines will benefit from intense research in antigen discovery and adjuvant agents. Furthermore, it is likely that vaccines need to be combined with compounds that reverse major tolerogenic pathways that are constitutively active at the tumor site. Developing these combined approaches to vaccination in cancer promises new, exciting findings and, at the same time, poses important challenges to academic research institutions and the pharmaceutical industry.

The quest for blood pressure reference values in children

Do we need country-specific blood pressure reference values for children? This question will sound weird for clinicians caring for adult hypertensive patients or researchers working in the domain of adult hypertension. Indeed, there are no country-specific reference values for adults. This contrasts with hypertension in children, for whom there is an increasing number of published sets of country-specific reference values [1-5].

How important are interview methods and questionnaire designs in research on self-reported juvenile delinquency? An experimental comparison of internet vs. paper-and-pencil questionnaires and different definitions of the reference period

There has been relatively little change over recent decades in the methods used in research on self-reported delinquency. Face-to-face interviews and selfadministered interviews in the classroom are still the predominant alternatives envisaged. New methods have been brought into the picture by recent computer technology, the Internet, and an increasing availability of computer equipment and Internet access in schools. In the autumn of 2004, a controlled experiment was conducted with 1,203 students in Lausanne (Switzerland), where "paper-and-pencil" questionnaires were compared with computer-assisted interviews through the Internet. The experiment included a test of two different definitions of the (same) reference period. After the introductory question ("Did you ever..."), students were asked how many times they had done it (or experienced it), if ever, "over the last 12 months" or "since the October 2003 vacation". Few significant differences were found between the results obtained by the two methods and for the two definitions of the reference period, in the answers concerning victimisation, self-reported delinquency, drug use, failure to respond (missing data). Students were found to be more motivated to respond through the Internet, take less time for filling out the questionnaire, and were apparently more confident of privacy, while the school principals were less reluctant to allow classes to be interviewed through the Internet. The Internet method also involves considerable cost reductions, which is a critical advantage if self-reported delinquency surveys are to become a routinely applied method of evaluation, particularly so in countries with limited resources. On balance, the Internet may be instrumental in making research on self-reported delinquency far more feasible in situations where limited resources so far have prevented its implementation.

Current features of infective endocarditis in elderly patients: results of the International Collaboration on Endocarditis Prospective Cohort Study.

BACKGROUND: Elderly patients are emerging as a population at high risk for infective endocarditis (IE). However, adequately sized prospective studies on the features of IE in elderly patients are lacking. METHODS: In this multinational, prospective, observational cohort study within the International Collaboration on Endocarditis, 2759 consecutive patients were enrolled from June 15, 2000, to December 1, 2005; 1056 patients with IE 65 years or older were compared with 1703 patients younger than 65 years. Risk factors, predisposing conditions, origin, clinical features, course, and outcome of IE were comprehensively analyzed. RESULTS: Elderly patients reported more frequently a hospitalization or an invasive procedure before IE onset. Diabetes mellitus and genitourinary and gastrointestinal cancer were the major predisposing conditions. Blood culture yield was higher among elderly patients with IE. The leading causative organism was Staphylococcus aureus, with a higher rate of methicillin resistance. Streptococcus bovis and enterococci were also significantly more prevalent. The clinical presentation of elderly patients with IE was remarkable for lower rates of embolism, immune-mediated phenomena, or septic complications. At both echocardiography and surgery, fewer vegetations and more abscesses were found, and the gain in the diagnostic yield of transesophageal echocardiography was significantly larger. Significantly fewer elderly patients underwent cardiac surgery (38.9% vs 53.5%; P < .001). Elderly patients with IE showed a higher rate of in-hospital death (24.9% vs 12.8%; P < .001), and age older than 65 years was an independent predictor of mortality. CONCLUSIONS: In this large prospective study, increasing age emerges as a major determinant of the clinical characteristics of IE. Lower rates of surgical treatment and high mortality are the most prominent features of elderly patients with IE. Efforts should be made to prevent health care-associated acquisition and improve outcomes in this major subgroup of patients with IE.

Allergen-specific immunotherapy of allergy and asthma: current and future trends.

Allergen-specific immunotherapy is the only immunomodulatory and etiological therapy of allergy and asthma. Conventional specific immunotherapy (SIT) with whole-allergen extract is antigen specific, effective on multiple organs, efficient on asthma in defined conditions, provides long-lasting protection and is cost effective. Moreover, SIT is able to prevent the course of rhinitis to asthma. SIT has its drawbacks: the long duration of treatment, the unsatisfactory standardization of allergen extracts and a questionable safety level. Novel approaches are aimed at drastically reducing adverse anaphylactic events, shortening the duration of therapy and improving its efficacy. Novel promising approaches have based their formulation on a limited set of recombinant allergens or chimeric molecules as well as on hypoallergenic allergen fragments or peptides. The simultaneous use of adjuvants with immunomodulatory properties may contribute to improve both the safety and efficacy of allergen-SIT of allergy and asthma.

Predicting current and future spatial community patterns of plant functional traits

Community-level patterns of functional traits relate to community assembly and ecosystem functioning. By modelling the changes of different indices describing such patterns - trait means, extremes and diversity in communities - as a function of abiotic gradients, we could understand their drivers and build projections of the impact of global change on the functional components of biodiversity. We used five plant functional traits (vegetative height, specific leaf area, leaf dry matter content, leaf nitrogen content and seed mass) and non-woody vegetation plots to model several indices depicting community-level patterns of functional traits from a set of abiotic environmental variables (topographic, climatic and edaphic) over contrasting environmental conditions in a mountainous landscape. We performed a variation partitioning analysis to assess the relative importance of these variables for predicting patterns of functional traits in communities, and projected the best models under several climate change scenarios to examine future potential changes in vegetation functional properties. Not all indices of trait patterns within communities could be modelled with the same level of accuracy: the models for mean and extreme values of functional traits provided substantially better predictive accuracy than the models calibrated for diversity indices. Topographic and climatic factors were more important predictors of functional trait patterns within communities than edaphic predictors. Overall, model projections forecast an increase in mean vegetation height and in mean specific leaf area following climate warming. This trend was important at mid elevation particularly between 1000 and 2000 m asl. With this study we showed that topographic, climatic and edaphic variables can successfully model descriptors of community-level patterns of plant functional traits such as mean and extreme trait values. However, which factors determine the diversity of functional traits in plant communities remains unclear and requires more investigations.

Discordances in the application of different criteria for quantification of paediatric abdominal obesity: an analysis of two Swiss studies.

Several definitions of paediatric abdominal obesity have been proposed but it is unclear whether they lead to similar results. We assessed the prevalence of abdominal obesity using five different waist circumference-based definitions and their agreement with total body fat (TBF) and abdominal fat (AF). Data from 190 girls and 162 boys (Ballabeina), and from 134 girls and 113 boys (Kinder-Sportstudie, KISS) aged 5-11 years were used. TBF was assessed by bioimpedance (Ballabeina) or dual energy X-ray absorption (KISS). On the basis of the definition used, the prevalence of abdominal obesity varied between 3.1 and 49.4% in boys, and 4.7 and 55.5% in girls (Ballabeina), and between 1.8 and 36.3% in boys and 4.5 and 37.3% in girls (KISS). Among children considered as abdominally obese by at least one definition, 32.0 (Ballabeina) and 44.7% (KISS) were considered as such by at least two (out of five possible) definitions. Using excess TBF or AF as reference, the areas under the receiver operating curve varied between 0.577 and 0.762 (Ballabeina), and 0.583 and 0.818 (KISS). We conclude that current definitions of abdominal obesity in children lead to wide prevalence estimates and should not be used until a standard definition can be proposed.

Molecular investigation of lymph nodes in patients with colon cancer: a new road to better staging

Objective: Small nodal tumor infiltrates are identified by applying multilevel sectioning and immunohistochemistry (IHC) in addition to H&E (hematoxylin and eosin) stains of resected lymph nodes. However, the use of multilevel sectioning and IHC is very time-consuming and costly. The current standard analysis of lymph nodes in colon cancer patients is based on one slide per lymph node stained by H&E. A new molecular diagnostic system called ''One tep Nucleic Acid Amplification'' (OSNA) was designed for a more accurate detection of lymph node metastases. The objective of the present investigation was to compare the performance ofOSNAto current standard histology (H&E). We hypothesize that OSNA provides a better staging than the routine use of one slide H&E per lymph node.Methods: From 22 colon cancer patients 307 frozen lymph nodes were used to compare OSNA with H&E. The lymph nodes were cut into halves. One half of the lymph node was analyzed by OSNA. The semi-automated OSNA uses amplification of reverse-transcribed cytokeratin19 (CK19) mRNA directly from the homogenate. The remaining tissue was dedicated to histology, with 5 levels of H&E and IHC staining (CK19).Results: On routine evaluation of oneH&Eslide 7 patients were nodal positive (macro-metastases). All these patients were recognized by OSNA analysis as being positive (sensitivity 100%). Two of the remaining 15 patients had lymph node micro-metastases and 9 isolated tumor cells. For the patients with micrometastases both H&E and OSNA were positive in 1 of the 2 patients. For patients with isolated tumor cells, H&E was positive in 1/9 cases whereas OSNA was positive in 3/9 patients (IHC as a reference). There was only one case to be described as IHC negative/OSNA positive. On the basis of single lymph nodes the sensitivity of OSNA and the 5 levels of H&E and IHC was 94・5%.Conclusion: OSNA is a novel molecular tool for the detection of lymph node metastases in colon cancer patients which provides better staging compared to the current standard evaluation of one slide H&E stain. Since the use of OSNA allows the analysis of the whole lymph node, sampling bias and undetected tumor deposits due to uninvestigated material will be overcome. OSNA improves staging in colon cancer patients and may replace the current standard of H&E staining in the future.

Transcranial direct current stimulation for the treatment of focal hand dystonia.

The treatment of writer's cramp, a task-specific focal hand dystonia, needs new approaches. A deficiency of inhibition in the motor cortex might cause writer's cramp. Transcranial direct current stimulation modulates cortical excitability and may provide a therapeutic alternative. In this randomized, double-blind, sham-controlled study, we investigated the efficacy of cathodal stimulation of the contralateral motor cortex in 3 sessions in 1 week. Assessment over a 2-week period included clinical scales, subjective ratings, kinematic handwriting analysis, and neurophysiological evaluation. Twelve patients with unilateral dystonic writer's cramp were investigated; 6 received transcranial direct current and 6 sham stimulation. Cathodal transcranial direct current stimulation had no favorable effects on clinical scales and failed to restore normal handwriting kinematics and cortical inhibition. Subjective worsening remained unexplained, leading to premature study termination. Repeated sessions of cathodal transcranial direct current stimulation of the motor cortex yielded no favorable results supporting a therapeutic potential in writer's cramp.

Pharmacotherapeutic management of locally advanced prostate cancer: current status.

Locally advanced prostate cancer (LAPC) is a heterogeneous entity usually embracing T3-4 and/or pelvic lymph-node-positive disease in the absence of established metastases. Outcomes for LAPC with single therapies have traditionally been poor, leading to the investigation of adjuvant therapies. Prostate cancer is a hormonally sensitive tumour, which usually responds to pharmacological manipulation of the androgen receptor or its testosterone-related ligands. As such, androgen deprivation therapy (ADT) has become an important adjuvant strategy for the treatment of LAPC, particularly for patients managed primarily with radiotherapy. Such results have generally not been replicated in surgical patients. With increased use of ADT has come improved awareness of the numerous toxicities associated with long-term use of these agents, as well as the development of strategies for minimizing ADT exposure and actively managing adverse effects. Several trials are exploring agents to enhance radiation cell sensitivity as well as the application of adjuvant docetaxel, an agent with proven efficacy in the metastatic, castrate-resistant setting. The recent work showing activity of cabazitaxel, sipuleucel-T and abiraterone for castrate-resistant disease in the post-docetaxel setting will see these agents investigated in conjunction with definitive surgery and radiotherapy.