PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.

A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine phosphatase receptor-type C, also known as CD45) was recently reported to be genetically associated with the development of multiple sclerosis (MS). We performed an extensive evaluation of this polymorphism using large family-based and case-control comparisons. Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course.

[Personal factors of the ICF]. / Personbezogene Faktoren der ICF.

PURPOSE: The presentation aims at illustrating the draft proposal of personal factors of the ICF for German-speaking regions which has been published in 2010 by the working group ICF of Faculty II "Social Medicine and Rehabilitation" of the German Society for Social Medicine and Prevention, DGSMP. For this reason, each personal factor is illustrated by two examples. Thus, the benefit is intended to be convincing. METHODS: Applying a qualitative approach, the working group ICF consisting of members of various professions and institutions including a patients' representative selected for each item one example the factor serving as a facilitator and a second the factor serving as a barrier. RESULTS: The components of the personal factors, as proposed, are presented, each factor is accompanied by two examples. CONCLUSION: The presentation demonstrates the various possibilities of applying personal factors and intends to prove that the selection of items chosen makes sense. The process of a comprehensive discussion about the possible format of the component of personal factors in the ICF should lead to a further optimization of the proposal and the preparation of a discussion at an international level.

Cholecystectomy through single access endoscopic surgery: where do we stand?

Single access endoscopic surgery, also called laparoendoscopic single site surgery, single port access or single incision laparoscopic surgery has rapidly emerged in clinical practice for some specific indications. Among them single access cholecystectomy is rapidly diffusing in an attempt to improve cosmetic results, reduce parietal trauma, fasten recovery and answer patient's demand of this frequent surgery. While this approach is diffusing some limitations still persist in its feasibility, which have to be overcome by new development in instrumentations and refinement in techniques. And, on the other hand safety principle of minimally invasive cholecystectomy should be strictly respected to ensure our patients safe surgeries. Recent experiences and reports have shown that all these points can be respected, at least by experienced teams, while offering patients the first steps towards routine clinical scarless surgery. In this paper we will review the current status of cholecystectomy through single access endoscopic surgery regarding techniques, indications and results.

Randomized clinical trial of laparoendoscopic single-site versus conventional laparoscopic cholecystectomy.

BACKGROUND: Conventional laparoscopy with three or more ports remains the 'gold standard' for cholecystectomy, but a laparoendoscopic single-site (LESS) approach is emerging, designed to decrease parietal trauma and improve cosmesis. This study compared conventional laparoscopic (CL) with LESS cholecystectomy, with short-term clinical results as the main outcomes. METHODS: A randomized trial of CL and LESS cholecystectomies involving 150 patients was undertaken. Follow-up was for 1 month after surgery. The primary endpoint was body image results evaluated by means of validated scales. Secondary endpoints were: postoperative pain measured on a visual analogue scale, analgesia requirement, morbidity, quality of life (QoL) measured with Short Form 12, duration of operation, hospital stay, time to return to work and cost analysis. RESULTS: Operating times and complications were similar in the two groups. Two LESS procedures (3 per cent) were converted to two-port laparoscopy owing to difficulties with exposure, and one CL operation was achieved through a single port because extensive fibrous peritoneal adhesions prevented placement of other ports. There were three and four port-site seroma/haematomas in the LESS and CL groups respectively. Better pain profiles and lower analgesia requirements were recorded in the LESS group (P < 0·001). QoL, body image and scar scale results were also better (P < 0·001). Operative costs were higher for LESS procedures (P < 0·001), although median time to return to work was shorter (P = 0·003). CONCLUSION: LESS is an alternative to CL cholecystectomy associated with better cosmesis, body image, QoL and an improved postoperative pain profile.

Robot-assisted gastrectomy for cancer.

Minimally invasive approach for gastric cancer has gained increasing acceptance. Introduction of the da Vinci robotic system has allowed overcoming the technical limitations of standard laparoscopy. To date, several studies have been published reporting the feasibility of robot-assisted gastrectomy (RAG). The aim of this study is to extensively review all the published literature concerning RAG and to assess its value. Since 2003, this systematic review of the literature shows that 10 original studies reporting 199 RAG for cancer have been published worldwide. The authors analyzed operative time, blood loss, conversion rate, lymph nodes retrieval, complications, mortality, length of hospital stay and follow-up through a systematic review. Mean age was 63 years (range: 25-96). Mean operative times were 265 minutes and 334 minutes for total and subtotal gastrectomy respectively. Mean blood loss reported was 113 mL (range: 12-1400). Conversion rate was 2.5%. Average lymph nodes retrieval was 32 (range: 11-83). Twenty-nine complications were reported (14.6%). Mortality rate was 1.5%. Mean length of stay was 10 days (range: 3-175).This review demonstrates that RAG for cancer is not only feasible but also seems to be safe, with low mortality and acceptable morbidity. However, due to the lack of long-term follow-up and the limited number of published studies, it is relatively too early to draw definitive conclusions and/or to recommend the use of RAG for oncologic gastrectomy. Randomized controlled trials with long-term follow up are needed before this promising approach can eventually be generalized.

Robotic pancreatic resection: how far can we go?

Minimally invasive pancreatic resection remains one of the most challenging abdominal procedures. A wide diffusion of the laparoscopic approach for pancreatic resection is still waited. However, interest is growing since the introduction of robotics in this field and many reports have been published so far. Distal pancreatectomy with or without spleen-preservation, pancreaticoduodenectomy, total and middle pancreatectomy and even extended resections or reconstructions have been reported with good outcomes. This review reports and evaluates the robotic approach for such advanced pancreatic resections. While complex pancreatic resections are feasible and safe by a robotic approach, it is still very early to draw definitive conclusions. Further randomized and controlled studies are required to support a routine use of the robotic technology for pancreatic resection.

Transumbilical single incision laparoscopic sigmoidectomy for benign disease.

BACKGROUND: Transumbilical single incision laparoscopic surgery (SILS) has made its initial forays into clinical minimally invasive surgery. SILS combines in part the cosmetic advantage and decrease parietal trauma of natural orifice surgery, but allow operative realization with standard and validated laparoscopic instruments. We report here the first clinical transumbilical SILS sigmoidectomy for benign disease. METHOD: Preliminary experience with transumbilical single incision laparoscopic surgery (or embryonic natural orifice transluminal endoscopic surgery) sigmoidectomy in a female patient (34 years, BMI 22 kg/m(2)) with sigmoid stenosis caused by nodular endometriosis was reported. Transumbilical SILS treatment of pelvic endometriosis was performed during the same operation through cauterization. RESULTS: Transumbilical single incision laparoscopic sigmoidectomy was feasible with conventional laparoscopic instruments. The combined uses of straight and articulated laparoscopic instruments allow the avoidance of transparietal sling suture for exposition. Operative time for sigmoidectomy and endometriosis therapy was 125 min. No intra-operative or postoperative complications were recorded. SILS achieved excellent cosmetic results and may be associated with accelerated recovery. CONCLUSION: Transumbilical single incision laparoscopic sigmoidectomy is feasible by experienced laparoscopic surgeons using conventional laparoscopic instruments and staplers. The combined uses of strait and articulated instruments allow transumbilical SILS sigmoidectomy without the need for additional incision or transparietal sling suture. SILS sigmoidectomy may have the clinical advantage over NOTES of offering the safety of laparoscopic colectomy and the avoidance of vaginal access. It has to be determined if SILS offers benefit to the patient, except in cosmesis, compared with standard laparoscopic sigmoidectomy.

[Personal contextual factors of the ICF draft from the Working Group "ICF" of Specialty Group II of the Geman Society for Social Medicine and Prevention]. / Personbezogene Faktoren der ICF - Entwurf der AG "ICF" des Fachbereichs II der Deutschen Gesellschaft für Sozialmedizin und Prävention (DGSMP).

Personal contextual factors play an essential part in the ICF model in relation to patient-centred care. It is generally assumed that their classification must refer to the country-specific social and cultural setting and its particular linguistic terms. Therefore personal factors are not classified as yet by the WHO for general use. In Germany in 2006 a group of experts working on the medical advisory board of statutory health insurance published a proposal for a systematic classification of relevant personal factors to describe the background of an individual's life and living. This classification was now further analysed and thoroughly revised by a more comprehensive group of German specialists working in different health care insurances and institutions, authorised by the German Society for Social Medicine and Prevention (DGSMP), supported by German-speaking Swiss ICF specialists. This classification is published as work in progress intending to broaden and prepare the process of discussion for a consensus conference to be held in Germany in 2011.

[Patient's point of view on surgical innovations: for less traumatic surgery and enhanced recovery]. / Innovations chirurgicales et point de vue du patient: vers une chirurgie moins traumatisante et une réhabilitation accélérée.

Surgical innovations (associating LESS, NOTES, robotics, images software and Fast-track surgery) will allow a less and less invasive surgery. While these advances could be view as surgical or industrial marketing, or compared to the laparoscopic revolution, they simply answer patients' demand in a society changing its standard regarding: medical care, body image, recovery and rehabilitation. We will in this paper, according to results of a Google Survey analyzing population expectations of surgery, evaluate the interest of these surgical innovations. While, these innovations at least in part answers patients expectation, their therapeutic validity will have to be proved. It is our job, to foresee the future of surgery in accordance with health care system needs and patients expectation for adequate implementation of these innovations.

[Scarless surgery: reality through umbilical laparoendoscopic single site surgery (LESS)?]. / Une chirurgie sans trace: réalité grâce à la chirurgie par abord ombilical unique (LESS)?

Laparoendoscopic Single-Site Surgery (LESS) has made its fore ways into clinical practice, and allows foreseeing a less traumatic surgery without visible scar. Its development reminds the revolution associated with apparition of laparoscopy. Actual clinical experience gained showed that LESS is valid, seems as safe as conventional laparoscopy, while offering patients a surgery without trace. LESS development, which requires advanced laparoscopy training, has made surgeons and industry rethink surgical ergonomic thus allowing rapid technical innovations. These innovations will change minimally invasive surgery in a near future, if they did not already. We, now, have to control its evolution to build a safe and reasonable future for minimally invasive surgery combining patients' desire and safety, populations needs.

[Really so far from fast-track colorectal surgery in senior patients?]. / Vraiment si loin d'une approche fast-track chez les seniors après chirurgie colorectale?

Senior population (> or = 70 y) represents approximately 17% of Western population and account for 2/3 of all solids cancers of which > 50% are colorectal. Their treatment would request major abdominal surgery, often not offered because of senior age or fear of prohibitive morbidity. Fast-track programs reduce postoperative morbidity and hospital stay after elective colorectal surgery. According to few studies, this approach seems to be safe and feasible in senior patients. In our institution, mortality/morbidity rates were 0% and 37% after elective colorectal surgery in senior patients with standard care, with a median hospital stay of 13 days. Elective colorectal surgery should be offered to senior patients. However the relative high morbidity rate with standard care prompts us to initiate a specifically designed fast-track protocol in senior patients.

Chromatin three-dimensional interactions mediate genetic effects on gene expression.

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.

Trans-sacral (Kraske) approach for gastrointestinal stromal tumour of the lower rectum: old procedure for a new disease.

Gastrointestinal stromal tumours (GISTs) of the lower rectum are rare cancers from mesenchymatous origin, which are characterized by; 1) the absence of metastases in loco-regional lymph nodes; and 2) a tendency to grow opposite to the intestinal lumen. Thus, the two preferred surgical approaches for rectal adenocarcinomas (i.e. abdominal and transanal) are inappropriate for GISTs, due to: 1) the uselessness of total mesorectal excision; and 2) to the difficulty to locate the tumour with a transanal approach. We report here a case of a large GIST of the lower rectum which was successfully treated with a posterior trans-sacral approach. Lower rectum GISTs are good indications for the Kraske procedure, and this relatively new disease entity may contribute to the reintroduction of an old procedure into the armamentarium of 21(st) century colorectal surgeons.

[Splenic trauma: predictive factors for failure of non-operative management]. / Traumatisme de la rate: facteurs prédictifs d'échec du traitement non-opératoire.

INTRODUCTION: Non-operative management of blunt splenic injury in adults has been applied with increasing frequency. However, predictive criteria for successful non-operative management are still a matter of debate. METHODS: we retrospectively reviewed all cases of blunt splenic injury in adult patients from 1997 to 2006. RESULTS: Of 190 patients with blunt splenic trauma (median age: 33 years, range 16-98), 43.7% (n=83) underwent emergency surgical intervention (Group I), and 56.3% (n=105) of patients were admitted for conservative treatment of splenic trauma. Conservative treatment was successful in 76.6% (n=82) (Group II), while 23.4% (n=25) of patients required a laparotomy (Group III). Ultimately, 43.2% of patients were successfully managed non-operatively, and 56.9% underwent laparotomy. Mechanism of injury was not significantly different among three groups. Group I patients presented significantly more frequently with hypovolemic shock (p<0.01), associated injuries (p<0.01), and high grade of splenic injury (p<0.01). All patients with active bleeding as evidenced by extravasation on CT scan, underwent exploratory laparotomy. Failure of non-operative management increased significantly with splenic trauma grade (grade I (0%), grade II (22.6%), grade III (27.6%) and grade IV (40%), (p<0.01) and with quantity of hemoperitoneum (10.4% of patients with small, 22.2% of patient with moderate, and 47.8% with large hemoperitoneum). The median interval for conservative treatment failure was 3 days (range: 1-15). Splenic injuries were operatively controlled by splenectomy (91.6%) and splenorrhaphy (8.4%). CONCLUSION: Suitability of adult patients with blunt splenic injury for non-operative management may be predicted at initial presentation, based on hemodynamic status and associated injuries. The quantity of hemoperitoneum and magnitude of splenic injury are predictive factors for failure of conservative treatment. Early definition of these factors may help identify those patients likely to be successfully treated without laparotomy.

[Gastrointestinal stromal tumors (GIST)]. / Tumeurs stromales gastro-intestinales.

Gastrointestinal stromal tumors (GIST) are the most common digestive mesenchymal tumors. GIST characterized by over-expression of the tyrosine kinase receptor KIT. GIST span a wide clinical spectrum from benign to highly malignant. Surgery is the only curative treatment for GIST. Low malignant GIST have an excellent prognosis after surgical treatment (5 years survival rate > 90%). Highly malignant GIST have an extremely poor prognosis even after surgical resection (median survival < 12 months). The development of tyrosine kinase inhibitors has changed the management of unresectable GIST. One of them, imatinib mesylate, has been proved to improve survival of metastatic GIST. This paper reviews literature data on GIST.

[Scarless surgery: myth or reality through NOTES?]. / Chirurgie sans cicatrice: mythe ou réalité grâce a la chirurgie par les orifices naturels?

Natural orifice translumenal endoscopic surgery (NOTES) is an exciting concept bringing scarless surgery a reality consisting in body cavity and organs approach through natural orifices (digestive, female genital, urinary tracts). While new instrumentation necessitated by NOTES is still developing, multiple surgical procedures have been performed with success in human. Whenever this approach combining surgical and endoscopic expertise needs technical improvement and clinical validation, it will have a large impact on the future of surgery related to population demand for scarless surgery. The next decade, will show us if surgery will be performed through NOTES or if minimally invasive surgery will be positively influenced by the technical progress of NOTES to be the most minimally traumatic.

A consensus motif in the RFX DNA binding domain and binding domain mutants with altered specificity.

The RFX DNA binding domain is a novel motif that has been conserved in a growing number of dimeric DNA-binding proteins, having diverse regulatory functions, in eukaryotic organisms ranging from yeasts to humans. To characterize this novel motif, we have performed a detailed dissection of the site-specific DNA binding activity of RFX1, a prototypical member of the RFX family. First, we have performed a site selection procedure to define the consensus binding site of RFX1. Second, we have developed a new mutagenesis-selection procedure to derive a precise consensus motif, and to test the accuracy of a secondary structure prediction, for the RFX domain. Third, a modification of this procedure has allowed us to isolate altered-specificity RFX1 mutants. These results should facilitate the identification both of additional candidate genes controlled by RFX1 and of new members of the RFX family. Moreover, the altered-specificity RFX1 mutants represent valuable tools that will permit the function of RFX1 to be analyzed in vivo without interference from the ubiquitously expressed endogenous protein. Finally, the simplicity, efficiency, and versatility of the selection procedure we have developed make it of general value for the determination of consensus motifs, and for the isolation of mutants exhibiting altered functional properties, for large protein domains involved in protein-DNA as well as protein-protein interactions.

Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene.

The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is a key regulator of lymphocyte proliferation. IL-2R alpha is rapidly and potently induced in T cells in response to mitogenic stimuli. Interleukin 2 (IL-2) stimulates IL-2R alpha. transcription, thereby amplifying expression of its own high-affinity receptor. IL-2R alpha transcription is at least in part controlled by two positive regulatory regions, PRRI and PRRII. PRRI is an inducible proximal enhancer, located between nucleotides -276 and -244, which contains NF-kappaB and SRE/CArG motifs. PRRII is a T-cell-specific enhancer, located between nucleotides -137 and -64, which binds the T-cell-specific Ets protein Elf-1 and HMG-I(Y) proteins. However, none of these proximal regions account for the induction of IL-2R alpha transcription by IL-2. To find new regulatory regions of the IL-2R alpha gene, 8.5 kb of the 5' end noncoding sequence of the IL-2R alpha gene have been sequenced. We identified an 86-nucleotide fragment that is 90% identical to the recently characterized murine IL-2-responsive element (mIL-2rE). This putative human IL-2rE, designated PRRIII, confers IL-2 responsiveness on a heterologous promoter. PRRIII contains a Stat protein binding site that overlaps with an EBS motif (GASd/EBSd). These are essential for IL-2 inducibility of PRRIII/CAT reporter constructs. IL-2 induced the binding of Stat5a and b proteins to the human GASd element. To confirm the physiological relevance of these findings, we carried out in vivo footprinting experiments which showed that stimulation of IL-2R alpha expression correlated with occupancy of the GASd element. Our data demonstrate a major role of the GASd/EBSd element in IL-2R alpha regulation and suggest that the T-cell-specific Elf-1 factor can serve as a transcriptional repressor.

Characterization of a new tissue-specific transcription factor binding to the simian virus 40 enhancer TC-II (NF-kappa B) element.

We have biochemically and functionally characterized a new transcription factor, NP-TCII, which is present in nuclei from unstimulated T and B lymphocytes but is not found in nonhematopoietic cells. This factor has a DNA-binding specificity similar to that of NF-kappa B but is unrelated to this or other Rel proteins by functional and biochemical criteria. It can also be distinguished from other previously described lymphocyte-specific DNA-binding proteins.

Regulatory elements and expression profiles.

There has been steady progress in the computational analysis of transcription control regions, but current methods of predicting the gene regulatory features of noncoding sequences are still not accurate enough to be useful in automatic genome annotation. Therefore, detailed information on the expression patterns of newly sequenced genes is more likely to come from microarray-based high-throughput mRNA quantitation technologies, which have made revolutionary progress over the past few years and are now ready for genome-wide application. Future solutions to the regulatory element prediction problem may be found by the combined analysis of genome sequence and expression data.