Metastatic tumors to the colon and rectum: a multi-institutional study.

Context.-Unlike the small bowel, the colorectal mucosa is seldom the site of metastatic disease. Objective.-To determine the incidence of truly colorectal metastases, and subsequent clinicopathologic findings, in a substantial colorectal cancer population collected from 7 European centers. Design.-During the last decade, 10 365 patients were identified as having colorectal malignant tumors, other than systemic diseases. Data collected included patient demographics, clinical symptoms, treatment, the presence of metastases in other sites, disease-free interval, follow-up, and overall survival. All secondary tumors resulting from direct invasion from malignant tumors of the contiguous organs were excluded, as well as those resulting from lymph node metastases or peritoneal seeding. Results.-Only 35 patients were included (10 men) with a median age of 59 years. They presented with obstruction, bleeding, abdominal pain, or perforation. The leading source of metastases was the breast, followed by melanoma. Metastases were synchronous in 3 cases. The mean disease-free interval for the remaining cases was 6.61 years. Surgical resection was performed in 28 cases. Follow-up was available for 26 patients; all had died, with a mean survival time of 10.67 months (range, 1-41 months). Conclusions.-Colorectal metastases are exceptional (0.338%) with the breast as a leading source of metastases; they still represent a late stage of disease and reflect a poor prognosis. Therefore, the pathologist should be alert for the possibility of secondary tumors when studying large bowel biopsies. Any therapy is usually palliative, but our results suggest that prolonged survival after surgery and complementary therapy can be obtained in some patients.

Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study.

BACKGROUND: To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). METHODS: A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5-54). Median follow-up was 12.0 months. RESULTS: During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (< or = 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA > or = 2.5 (p = 0.01), KPS > or = 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. CONCLUSIONS: The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.

Intraoperative adverse events during laparoscopic colorectal resection-better laparoscopic treatment but unchanged incidence. Lessons learnt from a Swiss multi-institutional analysis of 3,928 patients.

PURPOSE: Intraoperative adverse events significantly influence morbidity and mortality of laparoscopic colorectal resections. Over an 11-year period, the changes of occurrence of such intraoperative adverse events were assessed in this study. METHODS: Analysis of 3,928 patients undergoing elective laparoscopic colorectal resection based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery was performed. RESULTS: Overall, 377 intraoperative adverse events occurred in 329 patients (overall incidence of 8.4 %). Of 377 events, 163 (43 %) were surgical complications and 214 (57 %) were nonsurgical adverse events. Surgical complications were iatrogenic injury to solid organs (n = 63; incidence of 1.6 %), bleeding (n = 62; 1.6 %), lesion by puncture (n = 25; 0.6 %), and intraoperative anastomotic leakage (n = 13; 0.3 %). Of note, 11 % of intraoperative organ/puncture lesions requiring re-intervention were missed intraoperatively. Nonsurgical adverse events were problems with equipment (n = 127; 3.2 %), anesthetic problems (n = 30; 0.8 %), and various (n = 57; 1.5 %). Over time, the rate of intraoperative adverse events decreased, but not significantly. Bleeding complications significantly decreased (p = 0.015), and equipment problems increased (p = 0.036). However, the rate of adverse events requiring conversion significantly decreased with time (p < 0.001). Patients with an intraoperative adverse event had a significantly higher rate of postoperative local and general morbidity (41.2 and 32.9 % vs. 18.0 and 17.2 %, p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Intraoperative surgical complications and adverse events in laparoscopic colorectal resections did not change significantly over time and are associated with an increased postoperative morbidity.

Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS: Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION: These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.

Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy.

OBJECTIVE: Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP). METHODS: Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR. RESULTS: Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047). CONCLUSION: We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.

Three essays in Swiss corporate governance

This dissertation is a combination of three relatively independent chapters on the subject of corporate governance. Corporate governance is presently at the epicenter of the global financial crisis. The lack of regulation and the misalignment of objectives have greatly contributed to the major crisis we are now in. Most governance research has been conducted in the United States in a context of widely held corporations and great executive power. It does not reflect the variety of situations around the world and we question the validity of this model in other contexts. The aim of this dissertation is to look at other governance models, in particular the Swiss corporate governance not only from a practical point of view, but also from a multi-theoretical approach. Traditional corporate governance literature has focused on the Anglo-American model that mainly follows the agency theory (Jensen and Meckling, 1976) in a shareholder-manager context, and overlooked other approaches. We focus on three different aspects of corporate governance using three different theories. First, we look at the ownership type of various corporations, using the agency theory in a context where issues between shareholders predominate over the typical shareholder-manager relationship. Second, we explore the adoption process of several governance mechanisms that, due to changes in legislation, has taken place in Switzerland since 2002. We use the institutional theory (DiMaggio and Powell, 1983), in a context where the environmental pressures are particularly high. Finally, we spotlight the board of directors as a key element of the governance of publicly listed corporations. Particularly, we focus on the independence of the board of directors, using a combination of the agency and resource dependence theories (Pfeffer, 1972; Pfeffer and Salancik, 1978).

Neither Bad Apple nor Bad Barrel: How the Societal Context Impacts Unethical Behavior in Organizations

Every time another corporate scandal captures media headlines, the 'bad apple vs. bad barrel' discussion starts anew. Yet this debate overlooks the influence of the broader societal context on organizational behavior. In this article, we argue that misbehaviors of organizations (the 'barrels') and their members (the 'apples') cannot be addressed properly without a clear understanding of their broader context (the 'larder'). Whereas previously, a strong societal framework dampened the practical application of the Homo economicus concept (business actors as perfectly rational and egocentric utility-maximizing agents without any moral concern), specialization, individualization and globalization led to a business world disembedded from broader societal norms. This emancipated business world promotes a literal interpretation of Homo economicus among business organizations and their members. Consequently, we argue that the first step toward 'healthier' apples and barrels is to sanitize the larder, that is, adapt the framework in which organizations and their members evolve.Chaque fois qu'un nouveau scandale fait la une des médias, la question de savoir si le problème se situe au niveau des individus (des 'pommes isolées') ou au niveau des organisations (les 'caisses de pommes') refait surface. Ce débat tend néanmoins à sous-estimer l'influence du contexte sociétal plus large sur le comportement dans les organisations. Dans cet article, nous soutenons l'idée que les scandales éthiques dans les organisations ou parmi leurs membres ne peuvent être compris correctement sans une vision plus précise de leur contexte plus large (la 'cave à pommes'). Si dans le passé un contexte sociétal fort permettait d'adoucir les applications pratiques de l'Homo economicus (qui considère l'acteur économique comme un agent parfaitement rationnel et égocentrique cherchant à maximiser son utilité sans réflexion morale), l'individualisation et la globalisation ont conduit à un monde économique désencastré et déconnecté des normes sociales plus larges. Ce monde économique autonome promouvoit une interprétation littérale de l'Homo economicus parmi les entreprises et leurs employés. Il en résulte que le premier pas vers des pommes moins pourries passe par un assainissement de la cave, c'est-à-dire l'adoption d'un cadre socio-normatif qui permet un recadrage du contexte dans lequel les organisations économiques et leurs acteurs agissent.

Perioperative in-stent thrombosis after lung resection performed within 3 months of coronary stenting

BACKGROUND: Incidence of perioperative in-stent thrombosis associated with myocardial infarction in patients undergoing major lung resection within 3 months of coronary stenting. METHODS: Retrospective multi-institutional trial including all patients undergoing major lung resection (lobectomy or pneumonectomy) within 3 months of coronary stenting with non-drug-eluting stents between 1999 and 2004. RESULTS: There were 32 patients (29 men and 3 women), with age ranging from 46 to 82 years. One, two or four coronary stents were deployed in 72%, 22% and 6% of the patients, respectively. The time intervals between stenting and lung surgery were <30 days, 30-60 days and 61-90 days in 22%, 53% and 25% of the patients, respectively. All patients had dual antiplatelet therapy after stenting. Perioperative medication consisted of heparin alone or heparin plus aspirin in 34% and 66% of the patients, respectively. Perioperative in-stent thrombosis with myocardial infarction occurred in three patients (9%) with fatal outcome in one (3%). Twenty patients underwent lung resection after 4 weeks of dual antiplatelet therapy as recommended by the ACC/AHA Guideline Update; however, two out of three perioperative in-stent thrombosis occurred in this group of patients. CONCLUSIONS: Major lung resection performed within 3 months of coronary stenting may be complicated by perioperative in-stent thrombosis despite 4 weeks of dual antiplatelet therapy after stenting as recommended by the ACC/AHA Guideline Update.

Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND: Application of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for perioperative care for gastrectomy. METHODS: An international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated 'high', 'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or 'weak'. RESULTS: The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSION: The present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.

Les limites de la performativité des énoncés économiques: les apports de John Searle

The problematic of performativity has recently produced several criticisms and debates about the status of the economic discourse. Indeed the affirmation that economist shapes the world by describing it could leads to the subjectivist idea that each theory can in fine be 'true' and each theory can perform the social world in his specific way. This work clarifies this problematic in connecting it with the institutional theory of John Searle. We define performativity as a particular type of assignment of function. Finally, this enables us to show that performativity is limited by two kinds of factors : brut facts and social facts.

Managing Social-Business Tensions: A Review and Research Agenda for Social Enterprise

In a world filled with poverty, environmental degradation, and moral injustice, social enterprises offer a ray of hope. These organizations seek to achieve social missions through business ventures. Yet social missions and business ventures are associated with divergent goals, values, norms, and identities. Attending to them simultaneously creates tensions, competing demands, and ethical dilemmas. Effectively understanding social enterprises therefore depends on insight into the nature and management of these tensions. While existing research recognizes tensions between social missions and business ventures, we lack any systematic analysis. Our paper addresses this issue. We first categorize the types of tensions that arise between social missions and business ventures, emphasizing their prevalence and variety. We then explore how four different organizational theories offer insight into these tensions, and we develop an agenda for future research. We end by arguing that a focus on social-business tensions not only expands insight into social enterprises, but also provides an opportunity for research on social enterprises to inform traditional organizational theories. Taken together, our analysis of tensions in social enterprises integrates and seeks to energize research on this expanding phenomenon.

Guidelines for perioperative care for pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND & AIMS: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS®) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.

Guidelines for Perioperative Care for Pancreaticoduodenectomy: Enhanced Recovery After Surgery (ERAS(®)) Society Recommendations.

BACKGROUND: Protocols for enhanced recovery provide comprehensive and evidence-based guidelines for best perioperative care. Protocol implementation may reduce complication rates and enhance functional recovery and, as a result of this, also reduce length-of-stay in hospital. There is no comprehensive framework available for pancreaticoduodenectomy. METHODS: An international working group constructed within the Enhanced Recovery After Surgery (ERAS(®)) Society constructed a comprehensive and evidence-based framework for best perioperative care for pancreaticoduodenectomy patients. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the GRADE system and reached through consensus in the group. The quality of evidence was rated "high", "moderate", "low" or "very low". Recommendations were graded as "strong" or "weak". RESULTS: Comprehensive guidelines are presented. Available evidence is summarised and recommendations given for 27 care items. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSIONS: The present evidence-based guidelines provide the necessary platform upon which to base a unified protocol for perioperative care for pancreaticoduodenectomy. A unified protocol allows for comparison between centres and across national borders. It facilitates multi-institutional prospective cohort registries and adequately powered randomised trials.

What treatment for periprosthetic shoulder infection? Results from a multicentre retrospective series.

PURPOSE: Controversy still exists as to the best surgical treatment for periprosthetic shoulder infections. The aim of this multi-institutional study was to review a continuous retrospective series of patients treated in four European centres and to assess the respective eradication rate of various treatment approaches. METHODS: Forty-four patients were available for this retrospective follow-up evaluation. Functional and clinical evaluation of treatment for infection was performed using the Constant-Murley score, visual analogue scale and patient satisfaction Neer score. Erythrocyte sedimentation rate, serum leucocyte count and C-reactive protein were measured and shoulder X-ray examination performed prior to surgery and at the latest follow-up. RESULTS: At a mean follow-up of 41 months (range 24-98), 42 of 44 patients (95.5%) showed no signs of infection recurrence/persistence. Comparable eradication rates were observed after resection arthroplasty (100%; 6/6), two-stage revision (17/17) or permanent antibiotic-loaded spacer implant (93.3%; 14/15). No patient was treated by one-stage revision. On average, both functional and pain scores improved significantly; the worst joint function was observed after resection arthroplasty. CONCLUSIONS: This retrospective analysis conducted on the largest published series of patients to date shows comparable infection eradication rates after two-stage revision, resection arthroplasty or permanent spacer implant for the treatment of septic shoulder prosthesis.

Instruments for investigating fitness to drive - needs and expectations in primary care: a qualitative study

Background: Primary care physicians are often requested to assess their patients' fitness to drive. Little is however known on their needs to help them in this task. Aims: The aim of this study is to develop theories on needs, expectations, and barriers for clinical instruments helping physicians assess fitness to drive in primary care. Methods: This qualitative study used semi-structured interviews to investigate needs and expectations for instruments used to assess fitness to drive. From August 2011 to April 2013, we recorded opinions from five experts in traffic medicine, five primary care physicians, and five senior drivers. All interviews were integrally transcribed. Two independent researchers extracted, coded, and stratified categories relying on multi-grounded theory. All participants validated the final scheme. Results: Our theory suggests that for an instruments assessing fitness to drive to be implemented in primary care, it need to contribute to the decisional process. This requires at least five conditions: 1) it needs to reduce the range of uncertainty, 2) it needs to be adapted to local resources and possibilities, 3) it needs to be accepted by patients, 4) choices of tasks need to adaptable to clinical conditions, 5) and interpretation of results need to remain dependant of each patient's context. Discussion and conclusions: Most existing instruments assessing fitness to drive are not designed for primary care settings. Future instruments should also aim to support patient-centred dialogue, help anticipate driving cessation, and offer patients the opportunity to freely take their own decision on driving cessation as often as possible.