Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?

OBJECTIVE: To assess the therapeutic effect of the extent of lymph node dissection performed in patients with a stage pI non-small-cell lung cancer (NSCLC). METHODS: We analysed data on 465 patients with stage I NSCLC who were treated with surgical resection and some form of lymph node sampling. The median number of lymph node sampled was 10 and the median number of ipsilateral mediastinal lymph node stations sampled was two. We chose to define a procedure that harvested 10 or more lymph nodes and sampled two or more ipsilateral mediastinal stations as a lymphadenectomy, by contrast with sampling when one or both criteria were not satisfied. The effect of the surgical techniques: lymph node sampling (LS; n=207) vs. lymphadenectomy (LA; n=258) on 30-day mortality and overall survival were investigated. RESULTS: A total of 6244 lymph nodes was examined, including 4306 mediastinal lymph nodes. The mean (+/-SD) numbers of removed lymph nodes were 7+/-6.1 per patient following LS vs.18.6+/-9.3 following LA (P=0.001). An average mean of 1+/-0.90 mediastinal lymph node station per patient was sampled following LS vs. 2.7+/-0.8 following LA (P<10(-6)). Overall 30-day mortality rates were 2.4 and 3.1%, respectively. LA was disclosed as a favourable prognosticator at multivariate analysis (Hazard Risk: 1.43; 95% Confidence Interval: 1.00-2.04; P=0.048), together with younger patient age, absence of blood vessels invasion, and smaller tumour size. CONCLUSIONS: Importance of lymph node dissection affects patients outcome, while it does not enhance the operative mortality. A minimum of 10 lymph nodes assessed, and two mediastinal stations sampled are suggested as possible pragmatic markers of the quality of lymphadenectomy.     

Traumatic hip dislocation in childhood

Traumatic dislocation of the hip in childhood is uncommon and can be a consequence of minor trauma. The authors report a series of 35 dislocations in skeletally immature patients. Most were isolated posterior dislocations without acetabular lesions. In 75% of cases, reduction of the dislocation was easy. Nine children required surgery to remove interposed joint capsule and/or osteochondral fragments to achieve anatomic reduction. Outcomes were generally good, except in one patient in whom a displaced fracture of the femoral physis was followed by total head avascular necrosis. One case of partial necrosis had a satisfactory outcome. Epiphyseal necrosis, though uncommon, appeared to be inconsistent to prevent and hard to predict. Bone scan seems to be more effective than MRI for the detection of necrosis.     

Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule

OBJECTIVE: To assess oncologic outcome of patients treated by conservative radical surgery for tumors below 5 cm from the anal verge. SUMMARY BACKGROUND DATA: Standard surgical treatment of low rectal cancer below 5 cm from the anal verge is abdominoperineal resection. METHODS: From 1990 to 2003, patients with a nonfixed rectal carcinoma at 4.5 cm or less from the anal verge and without external sphincter infiltration underwent conservative surgery. Surgery included total mesorectal excision with intersphincteric resection, that is, removal of the internal sphincter, to achieve adequate distal margin. Patients with T3 disease or internal sphincter infiltration received preoperative radiotherapy. RESULTS: Ninety-two patients with a tumor at 3 (range 1.5-4.5) cm from the anal verge underwent conservative surgery. There was no mortality and morbidity was 27%. The rate of complete microscopic resection (R0) was 89%, with 98% negative distal margin and 89% negative circumferential margin. In 58 patients with a follow-up of more than 24 months, the rate of local recurrence was 2% and the 5-year overall and disease-free survival were 81% and 70%, respectively. CONCLUSIONS: The technique of intersphincteric resection permits us to achieve conservative surgery in patients with a tumor close to or in the anal canal without compromising local control and survival. Tumor distance from the anal verge is no longer a limit for sphincter-saving resection.     

Dobutamine improves thoracic aortic blood flow during off-pump coronary artery bypass surgery: results of a prospective randomised controlled trial.

OBJECTIVE: Dobutamine is commonly used to improve ventricular performance in cardiac surgery. The aim of this prospective randomised controlled study was to assess the effectiveness of using low doses of dobutamine during off-pump coronary artery bypass (OPCAB) surgery in order to reduce haemodynamic compromise due to heart displacement. METHODS: Thirty-two patients undergoing elective coronary artery bypass grafting (CABG) surgery using OPCAB technique for more than two vessels were approached and recruited. We analysed the changes in the thoracic aortic blood flow (TABF) during OPCAB using transoesophageal Doppler and by other conventional monitoring methods as cardiac output, invasive pulmonary and radial pressures and mixed venous oxygen saturation. RESULTS: The two groups were similar in preoperative characteristics. No postoperative complications were observed in the study patients. The heart rate, right atrial pressure, cardiac output measured by thermodilution and TABF changed significantly during the procedure. Also significant changes in descending thoracic aortic diameter were observed. The postoperative creatinine was significantly lower in the dobutamine group (P=0.04). Dobutamine was found responsible for the improvement in the descending TABF (P=0.006). CONCLUSIONS: This study showed that intra-operative intravenous infusion of dobutamine at 5 microg/kg per min in routine OPCAB patients safely increased cardiac output even without such changes been detected by conventional monitoring methods.     

Impact of colloid response on survival after preoperative radiotherapy in locally advanced rectal carcinoma

Neoadjuvant therapy for rectal carcinoma modifies morphology and natural history of the tumor. Colloid response defined by predominant colloid changes with or without residual tumor cells is a form of tumor response whose impact on survival is unknown. This study evaluated influence of tumor histologic response, especially of colloid response, on survival in patients treated by long-course preoperative radiotherapy for rectal cancer. In 200 patients with uT3-T4 or N1 rectal carcinomas, influence of type of surgery, dose of radiotherapy, residual tumor size, surface tumor aspect, tumor response (downstaging vs. colloid or no response), tumor grade, vascular and neural invasion, circumferential margin, and postoperative chemotherapy on 5-year overall and disease-free survival were studied by univariate and multivariate analyses. A colloid response was observed in 20% of the cases. Tumor response, circumferential margin, and vascular invasion were independently associated with the disease-free survival. Patients with downstaging had a better disease-free survival than patients without response (80% vs. 54%), whereas those with colloid response had an intermediate survival (64%). After colloid response, the rate of recurrence was similar to patients with downstaging for local recurrence (0%-3%) and to those with no response for distant recurrence (28%). After preoperative radiotherapy for rectal cancer, survival and type of recurrence are influenced by the tumor response. The intermediate natural history of patients with colloid response suggests taking colloid response into account in postoperative tumor staging to optimize adjuvant therapy.     

Relevance of Toll-like receptor-4 polymorphisms in renal transplantation

BACKGROUND: Polymorphisms in Toll-like receptor-4 (TLR4) have been reported to be associated with a blunted immune response to microbial pathogens, as well as a decreased risk of atherosclerosis in the general population. We assessed the impact of the two TLR4 variants on the risk of severe infection, the incidence of acute rejection, and the occurrence of atherosclerotic complications in renal transplant recipients (RTR). METHODS: TLR-4 polymorphisms were assessed in a cohort of 238 RTR. Post-transplant atherosclerotic events, acute rejection, severe bacterial infection, cytomegalovirus (CMV) disease, and opportunistic infections were evaluated as outcomes. RESULTS: The patients were followed for a mean duration of 95 +/- 29 months after transplant. TLR4 polymorphism was observed in 27 (11.3%) RTR. Subjects with TLR4 polymorphisms were less likely to experience post-transplant atherosclerotic events (RR 0.44; 95% CI 0.21 to 0.93; P= 0.02) and acute rejection (RR 0.41; 95% CI 0.30 to 0.83; P= 0.01), but presented severe bacterial infections (RR 1.33; 95% CI 1.12 to 1.67; P= 0.01) and opportunistic infections (RR 3.03; 95% CI 1.72 to 8.29; P= 0.008) more frequently. TLR4 polymorphism was marginally associated with CMV disease (RR 1.47; 95% CI 0.95 to 2.64; P= 0.08). CONCLUSION: RTR with TLR4 polymorphism present a lower risk of post-transplant atherosclerotic events and acute allograft rejection, but experience severe infectious episodes more frequently. This subset of RTR may benefit from a less potent immunosuppression regimen, along with increased preventive measures against infectious agents.     

Kidney Transplant in Black Recipients: Are African Europeans Different from African Americans?

Despite recent improvement, significant racial disparities in outcome still persist after renal transplantation among African American patients in the United States. This study evaluated the association of race and ethnicity with allograft outcomes in a French population of 952 Caucasian (Cauc) patients and 140 African European (AE) patients who underwent renal transplantation in our center between 1987 and 2003. Demographic characteristics were similar for the two cohorts other than cause of end-stage renal failure (more hypertension among AE and more polycystic kidney disease among Cauc) and cold ischemia time (significantly longer for AE). Immunosuppressive treatment was comparable between groups. There were no significant differences between AE and Cauc in the incidence of acute rejection (31% vs. 30%). At 5 years post-transplant, patient survival (93% vs. 92%), graft survival (83% in both groups) and graft function (creatinine clearance 48 mL/min vs. 45 mL/min) were also similar among the AE and Cauc patients. We demonstrate that ethnic origin does not affect outcome after renal transplantation in France. Therefore, differences observed in the United States cannot be only related to immunologic or pharmacologic factors. The results of renal transplantation in patients of African origin could be improved with universal immunosuppressive drug coverage.     

Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: the STRADIVARIUS randomized controlled trial

Context  Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease. Objective  To determine whether weight loss and metabolic effects of the selective cannabinoid type 1 receptor antagonist rimonabant reduces progression of coronary disease in patients with abdominal obesity and the metabolic syndrome. Design, Setting, and Patients  Randomized, double-blinded, placebo-controlled, 2-group, parallel-group trial (enrollment December 2004-December 2005) comparing rimonabant with placebo in 839 patients at 112 centers in North America, Europe, and Australia. Interventions  Patients received dietary counseling, were randomized to receive rimonabant (20 mg daily) or matching placebo, and underwent coronary intravascular ultrasonography at baseline (n = 839) and study completion (n = 676). Main Outcome Measures  The primary efficacy parameter was change in percent atheroma volume (PAV); the secondary efficacy parameter was change in normalized total atheroma volume (TAV). Results  In the rimonabant vs placebo groups, PAV (95% confidence interval [CI]) increased 0.25% (–0.04% to 0.54%) vs 0.51% (0.22% to 0.80%) (P = .22), respectively, and TAV decreased 2.2 mm³ (–4.09 to –0.24) vs an increase of 0.88 mm³ (–1.03 to 2.79) (P = .03). In the rimonabant vs placebo groups, imputing results based on baseline characteristics for patients not completing the trial, PAV increased 0.25% (–0.04% to 0.55%) vs 0.57% (0.29% to 0.84%) (P = .13), and TAV decreased 1.95 mm³ (–3.8 to –0.10) vs an increase of 1.19 mm³ (–0.73 to 3.12) (P = .02). Rimonabant-treated patients had a larger reduction in body weight (4.3 kg [–5.1 to –3.5] vs 0.5 kg [–1.3 to 0.3]) and greater decrease in waist circumference (4.5 cm [–5.4 to –3.7] vs 1.0 cm [–1.9 to –0.2]) (P < .001 for both comparisons). In the rimonabant vs placebo groups, high-density lipoprotein cholesterol levels increased 5.8 mg/dL (4.9 to 6.8) (22.4%) vs 1.8 mg/dL (0.9 to 2.7) (6.9%) (P < .001), and median triglyceride levels decreased 24.8 mg/dL (–35.4 to –17.3) (20.5%) vs 8.9 mg/dL (–14.2 to –1.8) (6.2%) (P < .001). Rimonabant-treated patients had greater decreases in high-sensitivity C-reactive protein (1.3 mg/dL [–1.7 to –1.2] [50.3%] vs 0.9 mg/dL [–1.4 to –0.5] [30.9%]) and less increase in glycated hemoglobin levels (0.11% [0.02% to 0.20%] vs 0.40% [0.31% to 0.49%]) (P < .001 for both comparisons). Psychiatric adverse effects were more common in the rimonabant group (43.4% vs 28.4%, P < .001). Conclusions  After 18 months of treatment, the study failed to show an effect for rimonabant on disease progression for the primary end point (PAV) but showed a favorable effect on the secondary end point (TAV). Determining whether rimonabant is useful in management of coronary disease will require additional imaging and outcomes trials, which are currently under way. Trial Registration  clinicaltrials.gov Identifier: NCT00124332      

Generalization of Frequency Discrimination Learning Across Frequencies and Ears: Implications for Underlying Neural Mechanisms in Humans

Frequency discrimination thresholds (FDTs) at 750, 1500, 3000, and 6000 Hz were measured in 32 normal-hearing listeners before and after each listener practiced the task for 12 h at one of the above frequencies using a single ear. Marked improvements in thresholds taking place over several hours were observed during the frequency- and ear-specific training period. Comparisons between pre- and posttraining thresholds showed large improvements at the trained frequency, but also at other frequencies. The improvements were initially slightly—but significantly—larger at the trained frequency than at untrained frequencies. However, this trained-frequency advantage disappeared rapidly during the course of the two-hour multifrequency posttraining session, suggesting rapid relearning or learning generalization across frequencies. In contrast, no significant ear specificity was found, not even at early stages of the posttraining session. These findings add to earlier results suggesting that, in humans, frequency discrimination learning is only weakly frequency-specific, and they reveal that a complete generalization across frequencies can occur rapidly with little retraining at the initially untrained frequencies. Implications regarding underlying mechanisms are discussed.     

Contact allergy in chronic leg ulcers: results of a multicentre study carried out in 423 patients and proposal for an updated series of patch tests

Background:  There is a lack of prospective studies investigating contact sensitization in patients with chronic leg ulcers.
Objectives:  To determine the frequency of contact sensitization in patients with chronic leg ulcers using a special series of patch tests and to determine whether the number of sensitizations was correlated with the duration of the chronic leg ulcers.
Patients/methods:  Multicentre study carried out in patients with chronic leg ulcers; patch tests with the European baseline series and with an additional 34 individual allergens or mixes and 3 commercial products.
Results:  Of the 423 patients (301 women, 122 men, mean age 68.5 years) with chronic leg ulcers, 308 (73%) had at least one positive patch test with 3.65 positive patch tests per patient. The main allergens were Myroxylon pereirae (41%), fragrance mix I (26.5%), antiseptics (20%), and corticosteroids (8%). The number of positive tests per patient was not correlated with the cause of ulcer but was increased with the duration of the ulcer with a statistical difference between the group of the <1 year compared with the group >10 years duration.
Conclusions:  From this large prospective multicentre study, polysensitization is frequent in patients with chronic leg ulcers, increasing with the duration of the ulcer. We propose avoidance of topical antiseptics and ointments containing perfumes in patients with chronic leg ulcers and an updated patch test series for investigating these patients.