Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET.

PET using 18F-FDG is a promising technique to monitor response in oncology. Unfortunately, a multitude of analytic methods is in use. To date, it is not clear whether simplified methods could replace complex quantitative methods in routine clinical practice. The aim of this study was to select those methods that would qualify for further assessment in a future prospective response-monitoring study by comparing results with patient outcome. METHODS: Dynamic 18F-FDG PET scans were obtained on 2 groups of patients. First, 10 patients with advanced non-small cell lung cancer (NSCLC) were scanned on consecutive days before treatment to assess test-retest variability. Second, 30 scans were obtained on 19 patients with locally advanced NSCLC as part of an ongoing response-monitoring study. These scans were analyzed by 2 observers to assess observer variability. In addition, these studies were used to compare various methods with the gold standard, full kinetic analysis (nonlinear regression [NLR]). RESULTS: Using an image-derived input function, NLR showed excellent test-retest and observer agreement confirming that it could be used as a gold standard method. From a total of 34 analytic methods, 10 showed good correlation with NLR. Taking into account the degree of complexity of the methods, 4 remain for further evaluation. CONCLUSION: The optimal method for analysis of 18F-FDG PET data was determined for several levels of complexity. Four methods need to be evaluated further to determine the optimal trade-off between simplicity and accuracy for routine clinical practice.     

Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure

BACKGROUND: While the antihypertensive and renoprotective potency of angiotensin-converting enzyme (ACE) inhibitors is well-established in adults with hypertension and/or chronic renal failure, little experience exists in pediatric chronic kidney disease. METHODS: As part of a prospective assessment of the renoprotective efficacy of ACE inhibition and intensified blood pressure (BP) control, 397 children (ages 3 to 18 years) with chronic renal failure [CRF; glomerular filtration rate (GFR) 11 to 80 mL/min/1.73 m2] and elevated or high-normal BP received ramipril (6 mg/m2) following a 6-month run-in period including a two-month washout of any previous ACE inhibitors. Drug efficacy was assessed by two monthly office BP and proteinuria assessments, and by ambulatory BP monitoring at start and after 6 months of treatment. RESULTS: In the 352 patients completing six months of treatment, 24-hour mean arterial pressure (MAP) had decreased by a mean of 11.5 mm Hg (-2.2 SDS) in initially hypertensive subjects, but only by 4.4 mm Hg (-0.8 SDS) in patients with initially normal BP. A linear correlation was found between MAP at baseline and the change of MAP during treatment (r= 0.51; P < 0.0001). The antihypertensive response was independent of changes in concomitant antihypertensive medication or underlying renal disease. BP was reduced with equal efficacy during day- and nighttime. Urinary protein excretion was reduced by 50% on average, with similar relative efficacy in patients with hypo/dysplastic nephropathies and glomerulopathies. The magnitude of proteinuria reduction depended on baseline proteinuria (r= 0.32, P < 0.0001), and was correlated with the antihypertensive efficacy of the drug (r= 0.22, P < 0.001). The incidence of rapid rises in serum creatinine and progression to end-stage CRF during treatment did not differ from the pretreatment observation period. Mean serum potassium increased by 0.3 mmol/L. Ramipril was discontinued in three patients due to symptomatic hypotension or hyperkalemia. Hemoglobin levels decreased by 0.6 g/dL in the first two treatment months and remained stable thereafter. CONCLUSION: Ramipril appears to be an effective and safe antihypertensive and antiproteinuric agent in children with CRF-associated hypertension. The BP lowering and antiproteinuric effects are greatest in severely hypertensive and proteinuric children.     

Effects of xenon anaesthesia on intestinal oxygenation in acutely instrumented pigs

Background. Xenon is a narcotic gas that might be able to replacevolatile anaesthetics or nitrous oxide due to its favourablepharmacological properties, such as providing haemodynamic stability.Intestinal oxygenation is affected by most volatile anaestheticsas a result of cardiodepressive effects. Reducing oxygenationof the gut might be a factor leading to perioperative organdysfunction. This animal study was designed to assess the effectsof xenon on intestinal oxygenation. Methods. After ethical approval, 24 anaesthetized, acutely instrumentedpigs were randomly assigned to three groups: nine animals receivedxenon anaesthesia with inspiratory concentrations of 0, 20,50 and 65% in addition to their basic i.v. anaesthesia, nineanimals served as a study control group, and five animals wereused to assess model stability. Measurement of systemic andregional haemodynamic and oxygenation parameters was made 30min after changing the xenon concentration. Results. Xenon elicited dose-dependent systemic haemodynamicchanges: heart rate and cardiac output decreased by 30%, whilemean arterial pressure was stable. Superior mesenteric arteryblood flow was lower in the xenon group. Vascular resistanceof the superior mesenteric artery increased. The small intestinaloxygen supply decreased with increasing xenon concentration;the mucosal tissue oxygen partial pressure decreased but didnot reach hypoxic (<5 mm Hg) values. Serosal tissue oxygenpartial pressure was maintained. Conclusions. Xenon, in addition to basic i.v. anaesthesia, eliciteda decrease in cardiac output and maintained mean arterial pressure.Intestinal oxygenation was maintained, although regional macrohaemodynamicperfusion decreased. Xenon does not impair intestinal oxygenationunder physiological conditions.      

Psychosocial rehabilitation and satisfaction with life in adults with childhood-onset of end-stage renal disease

Little information is available on vocational rehabilitation and satisfaction with the quality of life in adult patients with early onset of end-stage renal disease (ESRD). A sample of 39 patients (mean age =26.7±6, range, 18 to 43 years, n =13 on dialysis, n =26 transplanted successfully) were required to report data on their vocational qualification and employment, and their degree of general and health-related satisfaction with life was surveyed. Data on psychosocial rehabilitation were collected by a structured questionnaire, whereas satisfaction with the quality of life was assessed with the standardized Questionnaire on Satisfaction in Life (FLZ). Fifty-eight percent of the patients had left school with certificates equivalent to high school graduation, 87% had completed vocational training and 67% were in paid employment. Forty-nine percent lived on their own or with a partner and 72% fully or partly earned their own living. The mean general and health-related satisfaction with life is significantly reduced compared to the general population. The patients were least satisfied in the areas partnership/sexuality and family life/offspring in general, as well as physical condition and ability to relax within health-orientated satisfaction. Final mean body height was 167.6±11.9 (SDS –1.54±1.59) for male and 153.77±8.29 for female patients (SDS –1.58±1.54). Thirty-six percent reported to be dissatisfied with their present body height compared to 4% of age-matched healthy controls. Positive perception of quality of life was significantly correlated to satisfaction with adult height ( r =0.41, P =0.008). Vocational rehabilitation of adult patients with early onset of ESRD achieves lower values than among the general population, however, more favorable percentages than among young adult patients or patients with adult onset of ESRD. The patients self-evaluation of both their general and health-related quality of life proves to be clearly muted, which is a clear indication of the physical and psychological strain of living with a chronic disease.     

Percutaneous Balloon Dilatation and Long-Term Drainage as Treatment of Anastomotic and Nonanastomotic Benign Biliary Strictures

Purpose

This study was designed to determine the effectiveness of percutaneous balloon dilation and long-term drainage of postoperative benign biliary strictures.

Methods

Medical records of patients with postoperative benign biliary strictures, in whom percutaneous transhepatic biliary drainage (PTBD) and balloon dilation was performed between January 1999 and December 2011, were retrospectively reviewed. PTBD and balloon dilation (4–10 mm) were followed by placement of internal-external biliary drainage catheters (8.5–12 F). Patients were scheduled for elective tube changes, if necessary combined with repeated balloon dilation of the stenosis, at 3-week intervals up to a minimum of 3 months.

Results

Ninety-eight patients received a total of 134 treatments. The treatment was considered technically successful in 98.5 %. Drainage catheters were left in with a median duration of 14 weeks. Complications occurred in 11 patients. In 13 patients, percutaneous treatment was converted to surgical intervention. Of 85 patients in whom percutaneous treatment was completed, 11.8 % developed clinically relevant restenosis. Median follow-up was 35 months. Probability of patency at 1, 2, 5, and 10 years was 0.95, 0.92, 0.88, and 0.72, respectively. Overall, 76.5 % had successful management with PTBD. Restenosis and treatment failure occurred more often in patients who underwent multiple treatments. Treatments failed more often in patients with multiple strictures. All blood markers of liver function significantly decreased to normal values.

Conclusions

Percutaneous balloon dilation and long-term drainage demonstrate good short- and long-term effectiveness as treatment for postoperative benign biliary strictures with an acceptably low complication rate and therefore are indicated as treatment of choice.     

Secondary effects of femoral instrumentation on pulmonary physiology in a standardised sheep model: what is the effect of lung contusion and reaming?

Intramedullary nailing is the treatment of choice for patients with femoral shaft fractures. However, there is an ongoing debate in multiple trauma patients with associated lung contusion when primary or secondary definitive stabilisation of the long bone fracture should be performed, as nailing is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS). In a standardised sheep model, this study aimed to quantify the development of acute pulmonary endothelial changes, to assess the activation of polymorphonuclear leucocytes (PMNL) and to observe the effects on the coagulation system associated with the reamed nailing procedure. Furthermore, the effect of coexisting lung contusion in an experimental model was evaluated. The animals were randomly assigned to one of four different groups (6 animals/group). In control groups, only a sham operation (thoracotomy) was performed, whereas in study groups, lung contusion was induced prior to femoral stabilisation either by external fixation or reamed femoral nailing. Using bronchoalveolar lavage (BAL) pulmonary permeability changes were quantified and PMNL activation was assessed by chemiluminescence. Additionally PMNL diapedesis and interstitial lung oedema were determined by histological analysis. All animals were sacrificed 4 h after the start of the femoral instrumentation. Without an associated lung injury, instrumentation of the femoral canal with the reamed nailing technique induced a transient increase in pulmonary permeability. In the face of an induced lung contusion, reamed femoral nailing resulted in significant increases in PMNL activation, pulmonary permeability and interstitial lung oedema, compared with external fixation. Without pulmonary contusion, reaming of the femoral canal was associated with a transient increase in pulmonary permeability. This was exacerbated in the presence of lung contusion along with increased PMNL activation. External fixation did not provoke similar changes. The findings of this study support the view that reaming of the femoral canal should be avoided in polytrauma patients with severe chest trauma as it could act as an additional stimulus for adverse outcome. Temporary external fixation appears to be a safe method for fracture stabilisation until inflammatory and coagulatory disturbances after trauma have been normalized.     

Epithelial–mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma

Purpose

To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.

Methods

We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan–Meier analysis and uni- and multivariate Cox regression analysis.

Results

Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan–Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.

Conclusion

Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.