Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Background: Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. Objective: To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. Design: A prospective multicentre observational cohort study (the 'SONAR' study). Setting: Seventeen haemodialysis centres in the UK. Participants: Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Intervention: Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Main outcome measures: Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. Results: A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Conclusions: Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. Trial Registration: This trial is registered as ISRCTN36033877 and ISRCTN17399438. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

For people with advanced kidney disease, haemodialysis is best provided by an 'arteriovenous fistula', which is created surgically by joining a vein onto an artery at the wrist or elbow. However, these take about 2 months to develop fully ('mature'), and as many as 3 out of 10 fail to do so. We asked whether we could use early ultrasound scanning of the fistula to identify those that are unlikely to mature. This would allow us to decide whether it would be practical to run a large, randomised trial to find out if using early ultrasound allows us to 'rescue' fistulas that would otherwise fail. We invited adults to undergo serial ultrasound scanning of their fistula in the first few weeks after it was created. We then analysed whether we could use the data from the early scans to identify those fistulas that were not going to mature by week 10. Of the 333 fistulas that were created, about two-thirds reached maturity by week 10. We found that an ultrasound scan 4 weeks after fistula creation could reliably identify those fistulas that were going to mature. However, of those fistulas predicted to fail, about one-third did eventually mature without further intervention, and even without knowing what the early scans showed, another third were successfully rescued by surgery or X-ray-guided treatment at a later stage. Performing an early ultrasound scan on a fistula can provide reassurance that it will mature and deliver trouble-free dialysis. However, because scans are poor at identifying fistulas that are unlikely to mature, we would not recommend their use to justify early surgery or X-ray-guided treatment in the expectation that this will improve outcomes.

Anaesthetic and perioperative considerations for extrapleural pneumonectomy and extended pleurectomy/decortication: a scoping review protocol.

INTRODUCTION: Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps. METHODS AND ANALYSIS: This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care. ETHICS AND DISSEMINATION: Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.

The Value of Systematic Reviews and Meta-Analyses in Surgery.

BACKGROUND: Systematic reviews and meta-analyses are generally regarded as sitting atop the hierarchy of clinical evidence. The unbiased summary of current evidence that a systematic review provides, along with the increased statistical power from larger numbers of patients, is invaluable in guiding clinical decision-making and development of practice guidelines. Surgical specialties have historically lagged behind other areas of medicine in the application of evidence-based medicine, perhaps due to the unique challenges faced in the conduct of surgical clinical trials. These challenges extend to the conduct of systematic reviews, due to issues with the quality and heterogeneity of the underlying literature. SUMMARY: Recent years have seen an improvement in the quality of randomized controlled trials in surgical topics and an explosion in the publication of systematic reviews. This review explores recent trends in systematic reviews in surgery and discussed some of the aspects in conducting and interpreting reviews that are unique to surgical topics, including blinding, surgical heterogeneity and learning curves, patient and clinician preference, and industry involvement. Key Messages: Clinical trials, and therefore systematic reviews, of surgical interventions pose unique challenges which are important to consider when conducting them or applying the findings to clinical practice. Despite the challenges, systematic reviews still represent the best level of evidence for development of surgical practice guidelines.

Noninvasive biomarkers in monitoring kidney allograft health.

PURPOSE OF REVIEW: A key aspect of posttransplant management is to identify and treat graft injury before it becomes irreversible. The gold-standard for detection is histology, but biopsy is uncomfortable for the patient and carries a risk of complications. Detection of changes at a molecular level may preempt histological injury, and thereby identify injury earlier. RECENT FINDINGS: Indicators of immune system activation, such as candidate chemokines CXCL9 and CXCL10, and by-products of neutrophil activity, have been related to acute rejection and early allograft function. Transcriptomic studies of multiple-gene panels have identified candidate combinations that have proven very promising in risk-stratification and prediction of acute rejection, as well as diagnosis of both T-cell-mediated and antibody-mediated rejection. Serum and urine cell-free DNA is also a promising area of investigation, particularly in antibody-mediated rejection. SUMMARY: Noninvasive, rapid, and accurate tests for risk-prediction and diagnosis in renal transplant allografts are urgently required. The ideal candidate is one that can be measured in either urine or blood, is cheap, and is both sensitive and specific for the condition of interest. Numerous strategies have been proposed, with varying degrees of clinical and preclinical success. A few that meet the essential criteria have been evaluated; a few have made it as far as clinical testing.

Development of a Clinical Decision Support System for Living Kidney Donor Assessment Based on National Guidelines.

BACKGROUND: Live donor nephrectomy is an operation that places the donor at risk of complications without the possibility of medical benefit. Rigorous donor selection and assessment is therefore essential to ensure minimization of risk and for this reason robust national guidelines exist. Previous studies have demonstrated poor adherence to donor guidelines. METHODS: We developed a clinical decision support system (CDSS), based on national living donor guidelines, to facilitate the identification of contraindications, additional investigations, special considerations, and the decision as to nephrectomy side in potential living donors. The CDSS was then tested with patient data from 45 potential kidney donors. RESULTS: The CDSS comprises 17 core tasks completed by either patient or nurse, and 17 optional tasks that are triggered by certain patient demographics or conditions. Decision rules were able to identify contraindications, additional investigations, special considerations, and predicted operation side in our patient cohort. Seventeen of 45 patients went on to donate a kidney, of whom 7 had major contraindications defined in the national guidelines, many of which were not identified by the clinical team. Only 43% of additional investigations recommended by national guidelines were completed, with the most frequently missed investigations being oral glucose tolerance testing and routine cancer screening. CONCLUSIONS: We have demonstrated the feasibility of turning a complex set of national guidelines into an easy-to-use machine-readable CDSS. Comparison with real-world decisions suggests that use of this CDSS may improve compliance with guidelines and informed consent tailored to individual patient risks.

A systematic review of the use of rituximab for the treatment of antibody-mediated renal transplant rejection.

Rituximab is a B-lymphocyte depleting agent that is used to treat hematological malignancies and autoimmune diseases. Recently, it has gained interest as an immunomodulatory agent in renal transplantation. This systematic review evaluates the evidence for its use in the treatment of acute and chronic antibody-mediated renal transplant rejection (AAMR; CAMR). A systematic search of four databases and three trial registries was conducted. The small number and heterogeneous nature of included studies precluded meta-analysis and thus a narrative review was conducted. A total of 28 records met the inclusion criteria (AAMR, 18 records relating to 9 studies; CAMR, 10 records relating to 7 studies). Two systematic reviews were identified that had differing inclusion criteria to this current review. Of seven primary studies in the setting of AAMR, four reported increased graft survival and one reported improved graft function with rituximab. This contrasts with CAMR in which only one of seven studies reported improved graft outcomes with a rituximab-based regimen; three studies reported inferior outcomes and three reported no difference. Only one study reported that rituximab was associated with an increase in adverse effects. The included studies suggest that rituximab may be of some benefit in the setting of AAMR but a lack of high quality evidence precludes firm conclusions from being drawn. Rituximab does not appear to reliably improve outcomes in CAMR. Further well-conducted studies are required to better define the effects and long-term safety profile of rituximab in the treatment of antibody-mediated renal transplant rejection.

A National Registry Analysis of Kidney Allografts Preserved With Marshall's Solution in the United Kingdom.

BACKGROUND: The preservation fluids most commonly used for renal allograft preservation in the UK are University of Wisconsin Solution (UW, £120 per liter) and Marshall's Solution (hyperosmolar citrate, £10 per liter). The aim of this study was to compare the outcomes of deceased donor renal allografts preserved with these fluids using data from the UK national transplant registry. METHODS: Data regarding transplants performed between January 1, 2005, and December 31, 2008, was analyzed (n = 5027 kidneys). Kidneys from Donation after Brain Death (DBD) and Donation after Circulatory Death (DCD) were included. After univariate analysis, multivariate logistic and linear regression models were fitted for adult recipients of first grafts (n = 3703 kidneys). RESULTS: Marshall's solution was associated with longer cold ischemic time, older donors, kidney-only donors, donors with hypertension, and DBD (all P < 0.01). After adjusting for confounding, the choice of preservation fluid was not associated with the risk of PNF (OR, 0.82; 95% CI, 0.46-1.46; P = 0.50), DGF (OR, 1.22; 95% CI, 0.96-1.56; P = 0.11), acute rejection (OR, 0.95; 95% CI, 0.76-1.19; P = 0.63), renal function at 1 year (coefficient, 0.97; 95% CI, 0.91-1.04; P = 0.41), or graft survival (DBD HR, 0.71; 95% CI, 0.46-1.10; P = 12; DCD HR, 0.99; 95% CI, 0.58-1.73; P = 1.00). CONCLUSIONS: Marshall's solution has been used for the preservation of large numbers of kidneys in the UK. It is associated with transplant outcomes that are equivalent to those with UW solution. Thus, on the basis of this analysis and cost, a strong case can be made for the continued use of Marshall's solution as a preferred fluid for renal allograft preservation.

A systematic review of the use of rituximab as induction therapy in renal transplantation.

Rituximab is a B-lymphocyte depleting agent used to treat lymphoma and autoimmune diseases. There has been recent interest in its use both for management of highly-sensitised and ABO-incompatible recipients but also for induction therapy before transplantation. This systematic review evaluates the evidence for its use as part of induction protocols in ABO-compatible, non-sensitised recipients. 4 databases and 3 trial registries were searched for studies of the use of rituximab as part of induction protocols. The small number of identified studies precluded meta-analysis and thus a narrative review was conducted. 12 manuscripts met the inclusion criteria, relating to 5 individual studies. No significant improvements in patient and graft survival or acute rejection rates were identified with rituximab induction. A single small study reported a trend towards improved graft function with the addition of rituximab induction to a standard immunosuppressive regimen. Rituximab was not found to be associated with increased infectious complications in any study but concerns were raised over possible associations with leukopaenia and cardiovascular mortality. Overall, no convincing benefit of rituximab induction was found and some safety concerns were identified. The results of on-going trials are awaited but further studies may be required before we can draw firm conclusions regarding the efficacy and safety of rituximab in this setting.

A systematic review of the use of rituximab for desensitization in renal transplantation.

BACKGROUND: Rituximab is a B lymphocyte-depleting agent used to treat lymphoma and autoimmune diseases. Recently, it has been used for desensitization therapy in ABO-incompatible and highly sensitized recipients undergoing renal transplantation. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four databases and three trial registries were searched for studies comparing rituximab with non-rituximab desensitization protocols. A lack of randomized evidence precluded meta-analysis, and thus a narrative review was conducted. RESULTS: Forty-five records met the inclusion criteria, relating to 21 individual studies (two randomized controlled trials and 19 retrospective cohort studies). Ten studies investigated the use of rituximab in ABO-incompatible patients; most found no significant differences in patient and graft outcomes when compared most frequently to splenectomy-based protocols. Nine studies of limited quality focused on highly sensitized recipients (positive cross-match, donor-specific antibody, and elevated panel reactive antibody) and demonstrated some benefits in graft survival, acute and chronic rejection, and sensitization levels with rituximab. The remaining two studies combined ABO-incompatible and highly sensitized recipients and found no statistically significant increase in infectious complications with rituximab. CONCLUSION: Evidence of limited quality was identified to support the use of rituximab desensitization in highly sensitized recipients. Among ABO-incompatible recipients, rituximab was found to be equivalent to splenectomy, indicating that this invasive surgical procedure is not necessary. Further randomized controlled trials are required to better define the efficacy, long-term safety, and optimal dosing regimen of rituximab in this setting.

Graft vessel disease following heart transplantation: a systematic review of the role of statin therapy.

BACKGROUND: Graft vessel disease (GVD) is a significant cause of morbidity and mortality in cardiac allograft recipients. Hyperlipidemia is a risk factor for GVD, and the majority of patients will display abnormal lipid profiles in the years following transplant. OBJECTIVE: This systematic review aims to establish the clinical impact of statins in cardiac allograft recipients, critically appraising the literature on this subject. METHODS: A literature search for randomized studies assessing statin use in cardiac allograft recipients was undertaken. The Cochrane Central Registry of Controlled Trials, MEDLINE, EMBASE, clinicaltrials.gov, and the Transplant Library from the Centre for Evidence in Transplantation were searched. The primary outcome was presence of GVD. Secondary outcomes included graft and patient survival, acute rejection, and adverse events. Meta-analysis was precluded by heterogeneity in outcome reporting and therefore narrative synthesis was undertaken. RESULTS: Seven randomized controlled trials (RCTs) were identified. The majority of RCTs demonstrated some risk of bias, and methods of outcome measurement were variable. Studies reporting incidence or severity of GVD suggest that statins do confer benefit. Survival benefit from statin use is modest. There is a low incidence of adverse events attributable to statins. There was no difference in the overall number of episodes of rejection. CONCLUSION: Whilst the methodological quality of evidence describing the use of statins in cardiac allograft recipients is limited, the available evidence suggests benefit from their use. This is compatible with the effects of statins in non-transplant patients with cardiovascular disease. Furthermore, the rate of adverse events in the trials is low.

Outcomes after pulmonary metastasectomy for colorectal cancer.

BACKGROUND: Surgical resection offers the greatest likelihood of cure for appropriately selected patients with pulmonary colorectal carcinoma metastases. We hereby report our experience over the last 19 years at the Austin Hospital, Thoracic Surgery Unit. METHODS: This is a retrospective study of a consecutive series of patients with pulmonary colorectal cancer metastases. From 1994 to 2012, 66 patients underwent 83 pulmonary metastasectomies for colorectal cancer at the Austin Hospital. RESULTS: Seventy per cent of patients were operated on for single pulmonary metastases. The most common procedure performed was a video-assisted thoracoscopic surgery wedge resection. Median follow-up duration was 25 months. Three-, five-, seven- and ten-year survival was 53.4, 39.6, 34.6 and 23.1%, respectively. CONCLUSION: Pulmonary metastasectomy for metastatic colorectal carcinoma continues to offer the greatest survival advantage for appropriately selected patients.

The effect of preservation solutions for storage of liver allografts on transplant outcomes: a systematic review and meta-analysis.

OBJECTIVE: The objective of this review was to systematically evaluate the evidence comparing preservation fluids for liver allografts on transplant outcomes. BACKGROUND: Adequate preservation of liver allografts for transplantation is essential for successful transplant outcomes. There are several preservation fluids available that have been specifically designed for the static cold storage of livers. These fluids differ in composition and cost. METHODS: literature search was performed using MEDLINE, EMBASE, Cochrane Library, Transplant Library, and the International Clinical Trials Registry Platform. Only randomized controlled trials were included. Studies were assessed for methodological quality. Primary outcomes were the risk of early dysfunction, primary nonfunction, retransplantation, patient survival, and graft survival. Secondary outcomes were serum biochemical parameters in the first week and biliary complications. Summary effects were calculated as relative risk and relative log survival with 95% confidence intervals (95% CIs). RESULTS: Sixteen randomized controlled trials met the full inclusion criteria (1619 livers). There is good evidence that the University of Wisconsin and Celsior solutions are associated with the same rates of early dysfunction (relative risk = 1.08, 95% CI = 0.63-1.86, P = 0.77), primary nonfunction (relative risk = 0.73, 95% CI = 0.22-2.40, P = 0.60), patient survival (relative log survival = 0.86, 95% CI = 0.58-1.28, P = 0.46), and graft survival (relative log survival = 0.85, 95% CI = 0.59-1.23, P = 0.39). There was no good evidence of any difference in outcomes when comparing histidine-tryptophan-ketoglutarate with either of the University of Wisconsin or Celsior solution, although data were limited. CONCLUSIONS: Data from included studies suggest that preservation of deceased donor livers with the University of Wisconsin or Celsior solution results in equivalent outcomes.

Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Alemtuzumab (MabCampath or Campath; Genzyme, Cambridge, MA) is a CD52-specific monoclonal antibody that causes profound and sustained lymphocyte depletion. Its use as an induction therapy in organ transplantation is increasing. Since our last systematic review in 2006, where we identified the need for good-quality randomized controlled trials (RCTs), several RCTs have been published that examine its efficacy and safety in kidney transplantation. The aim of this study was to evaluate the current evidence for alemtuzumab induction therapy in kidney transplantation. METHODS: We performed a systematic literature search using Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Transplant Library from the Centre for Evidence in Transplantation, and International Clinical Trials Registry Platform. Inclusion criteria specified all RCTs in which kidney transplant recipients receiving induction with alemtuzumab were compared with those receiving another induction agent or no induction. Studies were assessed for methodological quality. The primary outcome was the incidence of biopsy-proven acute rejection (BPAR) (Banff grade ≥1), and secondary outcomes included graft loss, renal function, delayed graft function (DGF), patient death, and the incidence of infection, autoimmunity, malignancy, and new-onset diabetes mellitus after transplantation. RESULTS: Ten RCTs, with a total of 1223 patients, were included. Studies were grouped according to induction regimens. Alemtuzumab induction has a lower risk of BPAR compared with induction with the interleukin-2 receptor antibodies (IL-2RAs): basiliximab (Simulect; Novartis, Basel, Switzerland) and daclizumab (Zenapax; Roche, Basel, Switzerland) combined (relative risk, 0.54; 95% confidence interval, 0.37-0.79; P<0.01). No significant difference was observed in the risk of BPAR when alemtuzumab induction was compared with rabbit antithymocyte globulin (rATG) (Thymoglobulin [Genzyme] or ATG-Fresenius S [Fresenius, Munich, Germany]) (relative risk, 0.79; 95% confidence interval, 0.52-1.21; P=0.28). There was no difference in graft loss, DGF, patient death, and new-onset diabetes mellitus after transplantation when alemtuzumab was compared with IL-2RAs or rATG induction. The effect of alemtuzumab induction on renal function and the incidence of infection, malignancy, and autoimmunity were limited by the data available. There were two trials comparing alemtuzumab with no induction, but neither trial reported a significant reduction in BPAR at 12 months. CONCLUSIONS: Alemtuzumab induction reduces the risk of BPAR compared with IL-2RAs but not rATG. Because the incidence of other efficacy outcomes (graft loss, DGF, and patient death) was similar, if it is felt that an induction agent is necessary, then our analysis suggests that it is more acceptable to base the choice of induction agent on safety outcomes and/or costs.

VATS thymectomy for nonthymomatous myasthenia gravis: standardized outcome assessment using the myasthenia gravis foundation of America clinical classification.

OBJECTIVE: : Video-assisted thoracoscopic (VATS) thymectomy has been practiced in Australia for nearly two decades. Our aim was to assess the complete stable remission and asymptomatic disease rates after VATS thymectomy in nonthymomatous myasthenia gravis. There remains doubt that minimally invasive techniques achieve equal remission rates to open maximal operations. Therefore, we report our outcomes using the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification and Kaplan-Meier analysis and compare the results to the literature. METHODS: : A retrospective analysis of 78 consecutive patients undergoing right VATS thymectomy between April 1994 and March 2007 at two Thoracic Surgery Units in Melbourne, Australia, was undertaken. Patients with thymoma were excluded. Therefore, 57 patients were followed-up for a minimum of 12 months to apply the MGFA Clinical Classification. VATS thymectomy was performed by a three-port right side technique. RESULTS: : The complete stable remission rate was 15% at 3 years and 28% at 5 years. The asymptomatic disease rate was 59% at 5 years. Median follow-up was 32 months. No prognostic factors for remission were identified. The overall morbidity rate was 14% (8/57). CONCLUSIONS: : Right VATS thymectomy achieves comparable remission and asymptomatic disease rates to other minimally invasive and open techniques when compared with studies using either MGFA or older criteria.

Mycophenolate mofetil decreases acute rejection and may improve graft survival in renal transplant recipients when compared with azathioprine: a systematic review.

BACKGROUND: Mycophenolate mofetil (MMF) has increasingly replaced azathioprine (AZA) as the antimetabolite of choice in immunosuppressive protocols. Initial trials comparing MMF with AZA in patients receiving cyclosporine A sandimmune showed a clinical benefit in reducing the incidence of acute rejections. It has been questioned whether this benefit remains significant when using newer formulations of cyclosporine A (neoral) and tacrolimus. METHODS: Literature searches were performed using the Transplant Library, Cochrane library, Medline, and Embase for all randomized controlled trials directly comparing MMF with AZA in renal transplant recipients. Trials were assessed for quality using the Jadad scoring system. Trials were pooled using meta-analysis software. Confidence intervals were set at 95%. RESULTS: Nineteen relevant studies were identified, including a total of 3143 patients. MMF significantly reduces the risk of acute rejection when used in combination with any calcineurin inhibitor (relative risk 0.62, 0.55-0.87, P<0.00001). The hazard for graft loss, including death with a functioning graft, is also significantly reduced in patients treated with MMF (hazard ratio 0.76, 0.59-0.98, P=0.037). There is no significant difference in patient survival or renal transplant function between groups. Risk of adverse events, including cytomegalovirus infection, anemia, leukopenia or rates of malignancy, does not differ significantly. A greater risk of diarrhea is seen in MMF-treated patients. CONCLUSIONS: We have shown that MMF used with a calcineurin inhibitor does indeed confer a clinical benefit over AZA by reducing the risk of acute rejection and also possibly reducing graft loss. This effect is independent of whether MMF is used in combination with sandimmune, neoral or tacrolimus.

Pancoast tumors.

Pancoast tumors (superior sulcus tumors or apical lung tumors) typically invade structures at the thoracic outlet, including the inferior elements of the brachial plexus (C8, T1 nerve roots and lower trunk). Historically, these tumors are rapidly fatal, but newer treatment with induction chemotherapy and radiotherapy, followed by surgical resection of the tumor has resulted in improved patient survival. To accomplish oncologic excision, resection of the involved brachial plexus elements is still standard practice in most centers, resulting in loss of hand function and/or development of neuropathic pain. We present a modification of this protocol that incorporates induction chemoradiation, surgical resection of the lung tumor by a thoracic surgeon, and neurolysis and preservation of the brachial plexus by a neurosurgeon. Improved survival outcome, especially in patients demonstrating a pathologic complete response, with preservation of hand function, supports our hypothesis that involved brachial plexus does not need resection in these patients.

Lack of correlation of hypoxic cell fraction and angiogenesis with glucose metabolic rate in non-small cell lung cancer assessed by 18F-Fluoromisonidazole and 18F-FDG PET.

UNLABELLED: PET offers a noninvasive means to assess neoplasms, in view of its sensitivity and accuracy in staging tumors and potentially in monitoring treatment response. The aim of this study was to evaluate newly diagnosed non-small cell lung cancer (NSCLC) for the presence of hypoxia, as indicated by the uptake of (18)F-Fluoromisonidazole ((18)F-FMISO), and to examine the relationship of hypoxia to the uptake of (18)F-FDG, microvessel density, and other molecular markers of hypoxia. METHODS: Twenty-one patients with suspected or biopsy-proven NSCLC were enrolled prospectively in this study. All patients had PET studies with (18)F-FMISO and (18)F-FDG. Seventeen patients subsequently underwent surgery, with analysis performed for tumor markers of angiogenesis and hypoxia. RESULTS: In the 17 patients with resectable NSCLC (13 men, 4 women; age range, 51-77 y), the mean (18)F-FMISO uptake in tumor was significantly lower than that of (18)F-FDG uptake (P < 0.0001) and showed no correlation with (18)F-FDG uptake (r = 0.26). The mean (95% confidence interval [CI]) (18)F-FMISO SUV(max) (maximum standardized uptake value) was 1.20 [0.95-1.45] compared with the mean [95% CI] (18)F-FDG SUV(max) of 5.99 [4.62-7.35]. The correlation between (18)F-FMISO uptake, (18)F-FDG uptake, and tumor markers of hypoxia and angiogenesis was poor. A weakly positive correlation between (18)F-FMISO and (18)F-FDG uptake and Ki67 was found. CONCLUSION: The hypoxic cell fraction of primary NSCLC is consistently low, and there is no significant correlation in NSCLC between hypoxia and glucose metabolism in NSCLC assessed by (18)F-FDG. These findings have direct implications in understanding the role of angiogenesis and hypoxia in NSCLC biology.

Management of malignant mesothelioma by decortication and adjunct phototherapy.

Malignant mesothelioma is a relatively rare tumor that originates in the pleural space and almost invariably results from exposure to asbestos. Between September 1989 and December 1999, 100 patients were managed with curative intent using a combination of full decortication, adjunct phototherapy after administration of hematoporphyrin derivative, and strip radiotherapy to any areas where adequate clearance was not obtained. The survival curve was compared to that of 17 matched patients treated by decortication alone. Median survival increased from 250 to 440 days in the combined treatment group.