Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study

The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients (from 90 enrolled) underwent tumour resection after three 3-week cycles of docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2). Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no grade 4 nonhaematological toxicity was reported), with no observed late toxicities. Median overall survival (OS) and event-free survival (EFS) times were 35 and 15 months, respectively, in the 75 patients who underwent surgery; corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3 years after initiating trial therapy, 27 out of 75 patients (36%) were alive and tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and distant metastases, respectively. The most common sites of distant metastases were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of local relapse and distant metastases were complete tumour resection and chemotherapy activity (clinical response, pathologic response, mediastinal downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

MRI follow-up of TNF-dependent differential progression of atherosclerotic wall-thickening in mouse aortic arch from early to advanced stages

OBJECTIVES: An optimized, longitudinal in vivo magnetic resonance vessel wall-imaging protocol was evaluated regarding its capability of detecting differences in the time-dependent atherosclerotic lesion progression in the aortic arch between ApoE(-/-) and double-deficient ApoE(-/-)/TNF(-/-) mice at comparatively early plaque development stages. MATERIALS AND METHODS: Seven ApoE(-/-) and seven ApoE(-/-)/TNF(-/-) female mice underwent MRI at 11.75 teslas at four stages up to 26 weeks of age. A double-gated spin-echo MRI sequence was used with careful perpendicular slice positioning to visualize the vessel wall of the ascending aortic arch. RESULTS: Wall-thickness progression measured with MRI was significant at 11 weeks of age in ApoE(-/-) mice, but only at 26 weeks in ApoE(-/-)/TNF(-/-) mice. A significant correlation was found between MRI wall-thickness and lesion area determined on histology. CONCLUSION: MRI was shown to be sensitive enough to reveal subtle genetically-induced differences in lesion progression at ages earlier than 25 weeks.

Six-year follow-up of azathioprine and mycophenolate mofetil use during the first 6 months of renal transplantation

Long-term follow-up examination to test whether therapy with mycophenolate mofetil (MMF) or azathioprine (AZA) during the first year translates into different graft or patient survival and graft function is important. Therefore, 6-year follow-up data of a group of 80 consecutive renal transplant recipients were analyzed. The first group of 40 patients was treated with AZA, cyclosporine and prednisone and the second group with MMF, cyclosporine and prednisone for the first 6 months. Graft failure rates were compared during follow-up. Creatinine, inverse slope of creatinine (delta/creatinine) and 24-hour proteinuria at 6 years post transplantation were compared. The Kaplan-Meier analyses for death-censored and non-censored graft failure showed no difference between the groups. Creatinine values at 6 years for the AZA Group were 139 +/- 36 micromol/l (95% CI 125.9-151.2 micromol/l) and for the MMF Group 149 +/- 52 micromol/l (95% CI 133.9-164.9 micromol/l). Delta/creatinine and 24-hour proteinuria at 6 years did not differ between the two groups. We conclude that an initial 6-month treatment with MMF as opposed to AZA reduced the early rejection rate, but did not result in superior long-term graft function or survival after 6 years of follow-up observation.

The effect of matrix bound parathyroid hormone on bone regeneration

INTRODUCTION: Autogenous bone is the most successful bone-grafting material; however, multiple disadvantages continue to drive developments of improved methods for bone regeneration. AIM: The aim of the present study was to test the hypothesis that an arginine-glycine-aspartic acid (RGD) modified polyethylene glycol-based matrix (PEG) containing covalently bound peptides of the parathyroid hormone (PTH(1-34)) enhances bone regeneration to a degree similar to autogenous bone. MATERIAL AND METHODS: Six American foxhounds received a total of 48 cylindrical titanium implants placed in the mandible between the first premolar and the second molar. Five, respectively, 7 months following tooth extraction, implants were placed into the center of surgically created defects. This resulted in a circumferential bone defect simulating an alveolar defect with a circular gap of 1.5 mm. Four treatment modalities were randomly allocated to the four defects per side: (1) PEG-matrix containing 20 microg/ml of PTH(1-34), and 350 microg/ml cys-RGD peptide, (2) PEG alone, (3) autogenous bone and (4) empty defects. Histomorphometric analysis was performed 4 and 12 weeks after implantation. The area fraction of newly formed bone was determined within the former defect and the degree of bone-to-implant contact (BIC) was evaluated both in the defect region and in the apical region of the implant. For statistical analysis ANOVA and subsequent pairwise Student's t-test were applied. RESULTS: Healing was uneventful and all implants were histologically integrated. Histomorphometric analysis after 4 weeks showed an average area fraction of newly formed bone of 41.7+/-1.8% for matrix-PTH, 26.6+/-4.1% for PEG alone, 43.9+/-4.5% for autogenous bone, and 28.9+/-1.5% for empty defects. After 12 weeks, the respective values were 49.4+/-7.0% for matrix-PTH, 39.3+/-5.7% for PEG alone, 50.5+/-3.4% for autogenous bone and 38.7+/-1.9% for empty defects. Statistical analysis after 4 and 12 weeks revealed significantly more newly formed bone in the PTH(1-34) group compared with PEG alone or empty defects, whereas no difference could be detected against autogenous bone. Regarding BIC no significant difference was observed between the four treatment groups neither at 4 nor at 12 weeks. CONCLUSION: It is concluded that an RGD-modified PEG hydrogel containing PTH(1-34) is an effective matrix system to obtain bone regeneration.

Inappropriate interventions during the long-term follow-up of patients with an implantable defibrillator

QUESTIONS UNDER STUDY: In patients with an implantable defibrillator (ICD), inappropriate ICD interventions alter the quality of life, may cause hospitalisations and limit cost-effectiveness. The aim of the study was to determine the incidence and causes of inappropriate ICD interventions, and to identify patients at risk. METHODS: For this observational longitudinal study, consecutive patients undergoing ICD implantation at the University Hospital of Berne were included in a registry. All stored electrograms of episodes triggering ICD interventions were systematically reviewed and analysed to determine whether ICD interventions were appropriate or inappropriate. Inappropriate ICD interventions were classified according to their cause, and risk factors were sought. RESULTS: 214 consecutive patients were followed during a median time of 2.7 years (3.7 years IQR, 698 patient years). 81 inappropriate ICD interventions occurred in 58 patients (27%). Factors triggering inappropriate ICD interventions included atrial fibrillation and flutter (n = 35, 44%), sinus tachycardia (n = 26, 32%), lead fracture (n = 12), recurrent self-terminating ventricular tachycardia (n = 5), double-counting due to T-wave oversensing (n = 3). The only identifiable risk factor for inappropriate ICD interventions was sustained ventricular tachycardia as index arrhythmia. CONCLUSIONS: An important proportion of ICD patients suffer inappropriate ICD interventions that are most commonly due to supraventricular arrhythmias. Patients with ventricular tachycardia prior to ICD implantation are at higher risk of inappropriate ICD interventions. Interventions aiming at decreasing the risk of inappropriate ICD interventions should be considered in these patients.

Time-related, cross-sectional and prospective follow-up of pancreatic endocrine function after pancreas allograft transplantation in type 1 (insulin-dependent) diabetic patients

It has been established that successful pancreas transplantation in Type 1 (insulin-dependent) diabetic patients results in normal but exaggerated phasic glucose-induced insulin secretion, normal intravenous glucose disappearance rates, improved glucose recovery from insulin-induced hypoglycaemia, improved glucagon secretion during insulin-induced hypoglycaemia, but no alterations in pancreatic polypeptide responses to hypoglycaemia. However, previous reports have not segregated the data in terms of the length of time following successful transplantation and very little prospective data collected over time in individual patients has been published. This article reports that in general there are no significant differences in the level of improvement when comparing responses as early as three months post-operatively up to as long as two years post-operatively when examining the data cross-sectionally in patients who have successfully maintained their allografts. Moreover, this remarkable constancy in pancreatic islet function is also seen in a smaller group of patients who have been examined prospectively at various intervals post-operatively. It is concluded that successful pancreas transplantation results in remarkable improvements in Alpha and Beta cell but not PP cell function that are maintained for at least one to two years.

10-year follow-up of a prospective randomized trial comparing bare-metal stenting with internal mammary artery grafting for proximal, isolated de novo left anterior coronary artery stenosis the SIMA (Stenting versus Internal Mammary Artery grafting) trial

OBJECTIVES: This study was designed to compare the long-term clinical outcome of coronary artery bypass grafting (CABG) with intracoronary stenting of patients with isolated proximal left anterior descending coronary artery. BACKGROUND: Although numerous trials have compared coronary angioplasty with bypass surgery, none assessed the clinical evaluation in the long term. METHODS: We evaluated the 10-year clinical outcome in the SIMA (Stent versus Internal Mammary Artery grafting) trial. Patients were randomly assigned to stent implantation versus CABG. RESULTS: Of 123 randomized patients, 59 underwent CABG and 62 received a stent (2 patients were excluded). Follow-up after 10 years was obtained for 98% of the randomized patients. Twenty-six patients (42%) in the percutaneous coronary intervention group and 10 patients (17%) in the CABG group reached an end point (p < 0.001). This difference was due to a higher need for additional revascularization. The incidences of death and myocardial infarction were identical at 10%. Progression of the disease requiring additional revascularization was rare (5%) and was similar for the 2 groups. Stent thrombosis occurred in 2 patients (3%). Angina functional class showed no significant differences between the 2 groups. CONCLUSIONS: Both stent implantation and CABG are safe and highly effective in relieving symptoms in patients with isolated, proximal left anterior descending coronary artery stenosis. Stenting with bare-metal stents is associated with a higher need for repeat interventions. The long-term prognosis for these patients is excellent with either mode of revascularization.

Multimodality Preoperative Planning and Postoperative Follow-up of a Hybrid Cardiac Intervention

We describe the case of a 59-year-old man who had aortic regurgitation and a hypoplastic aortic valve and for whom an echocardiography evaluation revealed a vascular tumor in the roof of the left atrium, which was suspected to be a hemangioma. After undergoing preoperative invasive catheter coronary angiography, echocardiography, and multislice computed tomography examinations, the patient underwent an aortic miniroot replacement. Intraoperative findings confirmed the findings of the preoperative evaluations. The tumor, although macroscopically verified as a hemangioma, was not resected because of the tumor's position and size, and the threat of uncontrollable bleeding. After an uneventful postoperative clinical course, a subsequent successful transcatheter coil occlusion of the coronary fistula from the left circumflex coronary artery was performed as an alternative to surgical resection of the tumor. This case emphasizes the future role of a multimodality hybrid approach for diagnosis, planning (different 2- and 3-dimensional imaging modalities), and treatment in the form of combining interventional (transcatheter) and surgical (open heart) techniques, which could optimize different treatment strategies. This approach could be further improved by increasing the installations of hybrid operating rooms.

[Diagnosis, treatment and follow up of prostata cancer]

Prostate cancer is the most frequent diagnosed malignancy in men with an increasing incidence. In well informed men between the age of 50 and 70 years screening should be offered when requested. Not every newly diagnosed prostate cancer requires immediate treatment. Curative treatment should be offered to men with a minimal life expectancy of 10 years. In men older than 50-75 years, therefore further screening is not necessary due to a lack of a therapeutic consequence. Curative treatment options enclose as the gold standard surgical removal, i.e. open radical prostatectomy with pelvic lymph node dissection, and radio-oncologic treatments, be it percutaneous radiation therapy, brachytherapies or a combination thereof. Palliative treatment options are mainly hormonal treatment (medical or surgical androgen deprivation), local radiation, treatment with bisphosphonates, chemotherapy and surgical desobstruction of the prostate. Regular follow up allows for early detection of recurrences and an active treatment concept.

Long-term follow-up of metabolic activity in human alveolar echinococcosis using FDG-PET

AIM: [(18)F]fluoro-deoxyglucose positron-emission-tomography (FDG-PET) detects metabolic activity in alveolar echinococcosis (AE). The slow changes in metabolic and morphological characteristics require long-term follow-up of patients. This is the first study to evaluate metabolic activity over may years, hereby assessing the utility of FDG-PET for the evaluation of disease progression and response to treatment. PATIENTS, METHODS: 15 patients received a follow-up FDG-PET combined with computed tomography (integrated PET/CT) with a median of 6.5 years after the first PET in 1999. Number and location of enhanced metabolic activity in the area of AE lesions was determined. Quantification of intensity of metabolic activity was assessed by calculation of mean standardized uptake values. RESULTS: AE lesions in 11/15 patients had been metabolically inactive initially, but only two showed permanent inactivity over the course of 81 months. Interestingly, in two patients metabolic activity was newly detected after 80 and 82 months. Benzimidazole treatment was intermittently discontinued in seven cases. Persisting activity at FDG-PET demanded continued benzimidazole treatment in four patients. Neither treatment duration, lesional size, calcifications nor regressive changes correlated with metabolic activity. CONCLUSION: Treatment responses are heterogeneous and vary from progressive disease despite treatment to long-term inactive disease with discontinued treatment. Lack of metabolic activity indicates suppressed parasite activity and is not equivalent to parasite death. However, metabolic activity may remain suppressed for years, allowing for temporary treatment discontinuation. Relapses are reliably detected with PET and restarting benzimidazole treatment prevents parasite expansion.

Six-month angiographic follow-up of the PAS-Port II clinical trial

BACKGROUND: The PAS-Port device (Cardica, Redwood City, CA) allows the rapid deployment of a clampless proximal anastomosis between a vein graft and the aorta. METHODS: Fifty-four patients awaiting elective coronary artery bypass graft surgery were enrolled. Outcome variables were intraoperative device performance, early and 6- month angiographic graft patency, and 12-month clinical follow-up. RESULTS: Sixty-three PAS-Port devices were deployed in 54 patients. Two deployments were unsuccessful. There were no reoperations for bleeding. Two patients died of causes unrelated to the device. Patency evaluation at discharge was performed by angiogram on 49 implants and computed tomography in 2 implants (86% follow-up). At discharge, all evaluated grafts were patent (100%) and rated Fitzgibbon A. At 6-month follow-up, there was no additional mortality; 47 implants (88% follow-up) were evaluated by angiography (Fitzgibbon O [n = 1], Fitzgibbon B [n = 1], and Fitzgibbon A [n = 45]) and 5 by computed tomography. All grafts but 1 were patent (98.1%). At 12 months, 2 additional patients died of causes unrelated to the PAS-Port implant. Forty-six of 50 alive patients (95.8%) were followed up without any reports of device-related major adverse cardiac events. CONCLUSIONS: Discharge (100%) and 6-month patency (98%) are excellent; patency and 12 months' clinical follow-up compares favorably with data from historical hand-sewn controls. The PAS-Port system safely allows the clampless creation of a proximal anastomosis.

The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy

Molecular markers reliably predicting failure or success of Bacillus Calmette-Guérin (BCG) in the treatment of nonmuscle-invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty-eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow-up. Twenty-six of 68 (38%) NMIBC failed to BCG. Both positive post-BCG cytology and positive post-BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post-BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology.