The Tilburg double blind randomised controlled trial comparing inguinal hernia repair according to Lichtenstein and the transinguinal preperitoneal technique

<p>Abstract</p> <p>Background</p> <p>Anterior open treatment of the inguinal hernia with a tension free mesh has reduced the incidence of recurrence and direct postoperative pain. The Lichtenstein procedure rules nowadays as reference technique for hernia treatment. Not recurrences but chronic pain is the main postoperative complication in inguinal hernia repair after Lichtenstein's technique. Preliminary experiences with a soft mesh placed in the preperitoneal space showed good results and less chronic pain.</p> <p>Methods</p> <p>The TULIP is a double-blind randomised controlled trial in which 300 patients will be randomly allocated to anterior inguinal hernia repair according to Lichtenstein or the transinguinal preperitoneal technique with soft mesh. All unilateral primary inguinal hernia patients eligible for operation who meet inclusion criteria will be invited to participate in this trial. The primary endpoint will be direct postoperative- and chronic pain. Secondary endpoints are operation time, postoperative complications, hospital stay, costs, return to daily activities (e.g. work) and recurrence. Both groups will be evaluated.</p> <p>Success rate of hernia repair and complications will be measured as safeguard for quality.</p> <p>To demonstrate that inguinal hernia repair according to the transinguinal preperitoneal (TIPP) technique reduces postoperative pain to <10%, with α = 0,05 and power 80%, a total sample size of 300 patients was calculated.</p> <p>Discussion</p> <p>The TULIP trial is aimed to show a reduction in postoperative chronic pain after anterior hernia repair according to the transinguinal preperitoneal (TIPP) technique, compared to Lichtenstein.</p> <p>In our hypothesis the TIPP technique reduces chronic pain compared to Lichtenstein.</p> <p>Trial registration</p> <p>ISRCTN 93798494</p

Surrogate endpoints for overall survival in digestive oncology trials: which candidates? A questionnaires survey among clinicians and methodologists

<p>Abstract</p> <p>Background</p> <p>Overall survival (OS) is the gold standard for the demonstration of a clinical benefit in cancer trials. Replacement of OS by a surrogate endpoint allows to reduce trial duration. To date, few surrogate endpoints have been validated in digestive oncology. The aim of this study was to draw up an ordered list of potential surrogate endpoints for OS in digestive cancer trials, by way of a survey among clinicians and methodologists. Secondary objective was to obtain their opinion on surrogacy and quality of life (QoL).</p> <p>Methods</p> <p>In 2007 and 2008, self administered sequential questionnaires were sent to a panel of French clinicians and methodologists involved in the conduct of cancer clinical trials. In the first questionnaire, panellists were asked to choose the most important characteristics defining a surrogate among six proposals, to give advantages and drawbacks of the surrogates, and to answer questions about their validation and use. Then they had to suggest potential surrogate endpoints for OS in each of the following tumour sites: oesophagus, stomach, liver, pancreas, biliary tract, lymphoma, colon, rectum, and anus. They finally gave their opinion on QoL as surrogate endpoint. In the second questionnaire, they had to classify the previously proposed candidate surrogates from the most (position #1) to the least relevant in their opinion.</p> <p>Frequency at which the endpoints were chosen as first, second or third most relevant surrogates was calculated and served as final ranking.</p> <p>Results</p> <p>Response rate was 30% (24/80) in the first round and 20% (16/80) in the second one. Participants highlighted key points concerning surrogacy. In particular, they reminded that a surrogate endpoint is expected to predict clinical benefit in a well-defined therapeutic situation. Half of them thought it was not relevant to study QoL as surrogate for OS.</p> <p>DFS, in the neoadjuvant settings or early stages, and PFS, in the non operable or metastatic settings, were ranked first, with a frequency of more than 69% in 20 out of 22 settings. PFS was proposed in association with QoL in metastatic primary liver and stomach cancers (both 81%). This composite endpoint was ranked second in metastatic oesophageal (69%), colorectal (56%) and anal (56%) cancers, whereas QoL alone was also suggested in most metastatic situations.</p> <p>Other endpoints frequently suggested were R0 resection in the neoadjuvant settings (oesophagus (69%), stomach (56%), pancreas (75%) and biliary tract (63%)) and response. An unexpected endpoint was metastatic PFS in non operable oesophageal (31%) and pancreatic (44%) cancers. Quality and results of surgical procedures like sphincter preservation were also cited as eligible surrogate endpoints in rectal (19%) and anal (50% in case of localized disease) cancers. Except for alpha-FP kinetic in hepatocellular carcinoma (13%) and CA19-9 decline (6%) in pancreas, few endpoints based on biological or tumour markers were proposed.</p> <p>Conclusion</p> <p>The overall results should help prioritise the endpoints to be statistically evaluated as surrogate for OS, so that trialists and clinicians can rely on endpoints that ensure relevant clinical benefit to the patient.</p

Variables with time-varying effects and the Cox model: Some statistical concepts illustrated with a prognostic factor study in breast cancer

International audienceBACKGROUND: The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups. METHODS: We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered. RESULTS: Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups. CONCLUSIONS: Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise

Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration

The REMARK “elaboration and explanation” guideline, by Doug Altman and colleagues, provides a detailed reference for authors on important issues to consider when designing, conducting, and analyzing tumor marker prognostic studies

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe