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Background: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. Discussion: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5

Background: Lymphatic insufficiency might play a significant role in the pathophysiology of lipoedema. Liposuction is up to now the best treatment. As liposuction is invasive, the technique could destruct parts of the lymphatic system and by this aggravate the lymphatic component and/or induce lymphoedema. We investigated the function of the lymphatic system in lipoedema patients before and after tumescent liposuction and thus whether tumescent liposuction can be regarded as a safe treatment. Methods: Lymphoscintigraphy was performed to quantify the lymph outflow of 117 lipoedema patients. Mean clearance percentages of radioactive protein loaded after 1 min with respect to the total injected dose and corrected for decay of the radiopharmaceutical in the subcutaneous lymphatics were used as functional quantitative parameters as well as the clearance percentages and inguinal uptake 2 h post injection. The results of lymphatic function in lipoedema patients were compared with values obtained from normal healthy volunteers. We also compared 50 lymphoscintigraphies out of the previous 117 lipoedema patients before and six months after tumescent liposuction. Results: In 117 lipoedema patients clearance 2 h post injection in the right and left foot was disturbed in 79.5 and 87.2% respectively. The inguinal uptake 2 h post injection in the right and left groin was disturbed in 60.3 and 64.7% respectively. In 50 lipoedema patients mean clearance and inguinal uptake after tumescent liposuction were slightly improved, 0.01 (p = 0.37) versus 0.02 (p = 0.02), respectively. This is statistically not relevant in clearance. Conclusion: Lipoedema legs have a delayed lymph transport. Tumescent liposuction does not diminish the lymphatic function in lipoedema patients, thus tumescent liposuction can be regarded as a safe treatment.

Background: Both dobutamine stress echocardiography (DSE) and myocardial perfusion imaging (MPI) using single-photon emission computed tomography (SPECT) are frequently used for cardiac risk stratification. The long-term relative prognostic v

Background: Active surveillance after neoadjuvant therapies has emerged among several malignancies. During active surveillance, frequent assessments are performed to detect residual disease and surgery is only reserved for those patients in whom residual disease is proven or highly suspected without distant metastases. After neoadjuvant chemoradiotherapy (nCRT), nearly one-third of esophageal cancer patients achieve a pathologically complete response (pCR). Both patients that achieve a pCR and patients that harbor subclinical disseminated disease after nCRT could benefit from an active surveillance strategy. Summary: Esophagectomy is still the cornerstone of treatment in patients with esophageal cancer. Non-surgical treatment via definitive chemoradiotherapy (dCRT) is currently reserved only for patients not eligible for esophagectomy. Since salvage esophagectomy after dCRT (50-60 Gy) results in increased complications, morbidity and mortality compared to surgery after nCRT (41.4 Gy), the latter seems preferable in the setting of active surveillance. Clinical response evaluations can detect substantial (i.e., tumor regression grade [TRG] 3-4) tumors after nCRT with a sensitivity of 90%, minimizing the risk of development of non-resectable recurrences. Cu

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is standard of care for locally advanced esophageal cancer in many countries. After nCRT up to one third of all patients have a pathologically complete response in the resection specimen, posing an ethical impe

Background: It is not entirely clear whether ischemia burden on stress single-photon emission computed tomography (SPECT) effectively identifies patients who have a long-term benefit from coronary revascularization. Methods: The study population consisted of 719 patients with ischemia on stress SPECT. Early coronary revascularization was defined as percutaneous coronary intervention or coronary artery bypass grafting ≤90 days after SPECT. Patients who underwent late revascularization (>90 days after SPECT) were excluded (n = 164). Results: Of the 538 patients (73% men, mean age 59.8 ± 11 years), 348 patients had low ischemia burden (<3 ischemic segments) and 190 patients had moderate to high ischemia burden (≥3 ischemic segments). A total of 76 patients underwent early revascularization. During a median follow-up of 12 years (range 4-17), 283 patients died of whom 125 due to cardiac causes. Early revascularization was beneficial on all-cause mortality (HR 0.46, 95% CI 0.30-0.46) and cardiac mortality (HR 0.54, 95% CI 0.29-0.99). Conclusions: Patients with myocardial ischemia on stress SPECT who underwent early revascularization had a lower all-cause mortality and cardiac mortality during long-term follow-up as compared to patients who received pharmacological therapy alone. This difference in long-term outcomes was mainly influenced by the survival benefit of early revascularization in the patients with moderate to high ischemia burden.

Background. Exercise 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) is a useful tool for short- and medium-term risk stratifications. Curr

Objective. The goal of this study was to evaluate the very long-term outcome after normal exercise 99mTc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). Exercise 99mTc-sestamibi SPECT is widely used for risk stratification, but data on very long-term outcome after a normal test are scarce. Methods. A consecutive group of 233 patients (122 men, mean age 54 ± 12 years) with known or suspected coronary artery disease (CAD) underwent exercise 99mTc-sestamibi SPECT and had normal myocardial perfusion at exercise and at rest. Follow-up endpoints were allcause mortality, cardiac mortality, nonfatal myocardial infarction, and coronary revascularization. Predictors of outcome were identified by Cox proportional hazard regression models using clinical and exercise testing variables. Results. During amean follow-up of 15.5 ± 4.9 years, 41 (18%) patients died, of which 13were cardiac deaths. A total of 18 (8%) pa

Background Progressive supranuclear palsy (PSP) patients often exhibit cognitive decline and behavioural changes during the disease course. In a subset, these symptoms may be the presenting manifestation and can be similar to those in frontotemporal dementia (FTD). However, correlation studies between quantitative imaging measures and detailed neuropsychological assessment are scarce. The aim of this study was to investigate the functional role of affected brain regions in cognition in PSP compared with controls and subsequently examine these regions in FTD patients with known tau pathology (FTD tau). Methods 21 PSP patients, 27 healthy controls and 11 FTD tau patients were enrolled. All participants underwent neuropsychological testing and technetium99m-hexamethyl-propylenamine-oxime single photon emission CT. Regression slope analyses were performed in statistical parametric mapping to find significant associations between neuropsychological test results and brain perfusion. Results PSP patients showed hypoperfusion in the midcingulate cortex (MCC) of which the posterior part correlated with Stroop III and Weigl. In FTD tau patients, MCC involvement was located more anterior and correlated with Stroop III and Wisconsin Card Sorting Test concepts. The degree of hypoperfusion in the anterior cortex and MCC in the disorders differed in the subgenual anterior cingulate cortex only. Conclusions Th

Megalin-mediated renal retention of radiolabeled somatostatin analogs may lead to nephrotoxicity during peptide receptor radionuclide therapy (PRRT). The cytoprotective agent amifostine protected rats from long-term nephrotoxicity after PRRT with 177Lu-DOTA,Tyr3-octreotate. This study describes the direct effect of amifostine on kidney and tumor uptake of 111In- DOTA,Tyr3-octreotate. Methods: In vivo biodistribution studies were performed using CA20948 tumor-bearing rats, with or without amifostine coadministration, via several routes. In vitro uptake was studied in somatostatin receptor-expressing CA20948 and megalin or cubilin receptor-expressing BN-16 cells, in the absence or presence of amifostine or its active metabolite WR-1065. Results: Coadministration of amifostine decreased renal uptake of radiolabeled octreotate in vivo, whereas tumor uptake was not affected. In agreement, amifostine and WR-1065 coincubation reduced uptake in BN-16 but not in CA20948 cells. Conclusion: Amifostine may provide renal protection during PRRT using somatostatin analogs, both by mitigation of radiation damage and the currently observed reduction of absorbed kidney radiation dose. Copyright

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed.

Background: The aim of this study was to assess the accuracy of stress 99m technetium tetrofosmin myocardial perfusion imaging for the diagnosis of in stent stenosis (ISS). Methods: We studied 72 patients who underwent exercise or dobutamine stress 99m technetium tetrofosmin imaging, 0.9-0.5 years after percutaneous coronary interventions in which stents were deployed. Coronary angiography was performed within 3 months of the stress test. ISS was defined as ≥50% stenosis in a coronary segment with previous stenting. Significant coronary artery disease (CAD) was defined as ≥50% stenosis within or outside the stented coronary segment. Results: The stent was deployed in 1 coronary artery in 52 patients, and in 2 coronary arteries in 20 patients (a total of 92 detected in 42 (58%) patients (51 stents). Reversible perfusion abnormalities were present in 34 of patients w

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy.

OBJECTIVES: To assess whether quantification of myocardial systolic velocities by pulsed wave tissue Doppler imaging can differentiate between stunned, hibernating, and scarred myocardium. DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 70 patients with reduced left ventricular function caused by chronic coronary artery disease. METHODS: Pulsed wave tissue Doppler imaging was done close to the mitral annulus at rest and during low dose dobutamine; systolic ejection velocity (Vs) and the difference in Vs between low dose dobutamine and the resting value (DeltaVs) were assessed using a six segment model. Assessment of perfusion (with Tc-99m-tetrofosmin SPECT) and glucose utilisation (by 18F-fluorodeoxyglucose SPECT) was used to classify dysfunctional regions (by resting cross sectional echocardiography) as stunned, hibernating, or scarred. RESULTS: 253 of 420 regions (60%) were dysfunctional. Of these, 132 (52%) were classified as stunned, 25 (10%) as hibernating, and 96 (38%) as scarred. At rest, Vs in stunned, hibernating, and scar tissue was, respectively, 6.3 (1.8), 6.6 (2.2), and 5.5 (1.5) cm/s (p = 0.001 by ANOVA). There was a gradual decline in Vs during low dose dobutamine infusion between stunned, hibernating, and scar tissue (8.3 (2.6) v 7.8 (1.5) v 6.8 (1.9) cm/s, p < 0.001 by ANOVA). DeltaVs was higher in stunned (2.1 (1.9) cm/s) than in hibernating (1.2 (1.4) cm/s, p < 0.05) or scarred regions (1.3 (1.2) cm/s, p = 0.001). CONCLUSIONS: Quantitative tissue Doppler imaging showed a gradual reduction in regional velocities between stunned, hibernating, and scarred myocardium. Dobutamine induced contractile reserve was higher in stunned regions than in hibernating and scarred myocardium, reflecting different severities of myocardial damage

PURPOSE: To determine the long-term prognostic value of dobutamine stress technetium 99m (99mTc)-labeled sestamibi single photon emission computed tomography (SPECT) in patients with limited exercise capacity. MATERIALS AND METHODS: Clinical data and SPECT results were analyzed in 531 consecutive patients. Follow-up was successful in 528 (99.4%) patients; 55 underwent early revascularization and were excluded. Normal or abnormal findings were considered in the absence or presence of fixed and/or reversible perfusion defects. A summed stress score was calculated to estimate the extent and severity of perfusion defects. Univariate and multivariate Cox proportional hazards regression models were used to identify independent predictors of late cardiac events. The incremental value of myocardial perfusion scintigraphy over clinical variables in predicting events was determined according to two models. The probability of survival was calculated by using the Kaplan-Meier method. RESULTS: Findings were abnormal in 312 patients. During 8.0 years +/- 1.5 of follow-up (range, 4.5-10.6 years), cardiac death occurred in 67 patients (total deaths, 165); nonfatal myocardial infarction, in 34; and late revascularization, in 49. The annual rates for cardiac death, cardiac death or infarction, and all events were 0.9%, 1.2%, and 1.5%, respectively, after normal findings and 2.7%, 3.4%, and 4.4%, respectively, after abnormal findings (P <.05). In a multivariable Cox proportional hazards model, not only an abnormal finding but also the summed stress score provided incremental prognostic information in addition to clinical data. The hazard ratio for cardiac death was 1.09 (95% CI: 1.01, 1.18) per 1-unit increment of the summed stress score. CONCLUSION: The incremental prognostic value of dobutamine stress 99mTc-sestamibi SPECT over clinical data was maintained over an 8-year follow-up in patients with limited exercise capacity.

OBJECTIVE: To assess the prevalence of myocardial viability by technetium-99m (Tc-99m)-tetrofosmin/fluorine-18-fluorodeoxyglucose (FDG) single photon emission computed tomography (SPECT) in patients with ischaemic cardiomyopathy. DESIGN: A retrospective observational study. SETTING: Thoraxcenter Rotterdam (a tertiary referral centre). PATIENTS: 104 patients with chronic coronary artery disease and severely depressed left ventricular function presenting with heart failure symptoms. MAIN OUTCOME MEASURES: Prevalence of myocardial viability as evaluated by Tc-99m-tetrofosmin/FDG SPECT imaging. Two strategies for assessing viability in dysfunctional myocardium were used: perfusion imaging alone, and the combination of perfusion and metabolic imaging. RESULTS: On perfusion imaging alone, 56 patients (54%) had a significant amount of viable myocardium, whereas 48 patients (46%) did not. Among the 48 patients with no significant viability by perfusion imaging alone, seven additional patients (15%) had significantly viable myocardium on combined perfusion and metabolic imaging. Thus with a combination of perfusion and metabolic imaging, 63 patients (61%) had viable myocardium and 41 (39%) did not. CONCLUSIONS: On the basis of the presence of viable dysfunctional myocardium, 61% of patients with chronic coronary artery disease and depressed left ventricular ejection fraction presenting with heart failure symptoms may be considered for coronary revascularisation. The combination of perfusion and metabolic imaging identified more patients with significant viability than myocardial perfusion imaging alone.

OBJECTIVE: Exercise tolerance in patients with diabetes is frequently impaired due to noncardiac disease such as claudication and polyneuropathy. This study assesses the prognostic value of dobutamine stress myocardial perfusion imaging in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 207 consecutive diabetic patients who were unable to undergo exercise stress testing underwent dobutamine-atropine stress myocardial perfusion imaging. Follow-up was successful in 206 of 207 (99.5%) patients. A total of 12 patients underwent early (<60 days) revascularization and were excluded from the analysis. End points during follow-up were hard cardiac events, defined as cardiac death and nonfatal myocardial infarction. RESULTS: Abnormal myocardial perfusion was detected in 125 (64%) patients. During 4.1 +/- 2.4 years of follow-up, 73 (38%) deaths occurred, 36 (49%) of which were due to cardiac causes. Nonfatal myocardial infarction occurred in 7 (4%) patients, and 45 (23%) patients underwent late coronary revascularization. Cardiac death occurred in 2 of 69 (3%) patients with normal myocardial perfusion and in 34 of 125 (27%) patients with perfusion abnormalities (P < 0.0001). A multivariable Cox proportional hazard model demonstrated that, in addition to clinical and stress test data, an abnormal scan had an incremental prognostic value for prediction of cardiac death (hazard ratio 7.2, 95% CI 1.7-30). The summed stress score was an important predictor of cardiac death; the hazard ratio was 1.2 (95% CI 1.07-1.34) per one-unit increment. CONCLUSIONS: Dobutamine-atropine stress myocardial perfusion imaging provides additional prognostic information incremental to clinical data in patients with diabetes who are unable to undergo exercise stress testing.

OBJECTIVE: To determine whether, compared with fundamental imaging, second harmonic imaging can improve the accuracy of dobutamine stress echocardiography for identifying viable myocardium, using nuclear imaging as a reference. PATIENTS: 30 patients with chronic left ventricular dysfunction (mean (SD) age, 60 (8) years; 22 men). METHODS: Dobutamine stress echocardiography was carried out in all patients using both fundamental and second harmonic imaging. All patients underwent dual isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT) with (99m)technetium-tetrofosmin/(18)F-fluorodeoxyglucose on a separate day. Myocardial viability was considered present by dobutamine stress echocardiography when segments with severe dysfunction showed a biphasic sustained improvement or an ischaemic response. Viability criteria on DISA-SPECT were normal or mildly reduced perfusion and metabolism, or perfusion/metabolism mismatch. RESULTS: Using fundamental imaging, 330 segments showed severe dysfunction at baseline; 144 (44%) were considered viable. The agreement between dobutamine stress echocardiography by fundamental imaging and DISA-SPECT was 78%, kappa = 0.56. Using second harmonic imaging, 288 segments showed severe dysfunction; 138 (48%) were viable. The agreement between dobutamine stress echocardiography and DISA-SPECT was significantly better when second harmonic imaging was used (89%, kappa = 0.77, p = 0.001 v fundamental imaging). CONCLUSIONS: Second harmonic imaging applied during dobutamine stress echocardiography increases the agreement with DISA-SPECT for detecting myocardial viability.

OBJECTIVES: Cardiovascular disease is the leading cause of morbidity and mortality in the elderly. The evaluation of coronary artery disease by exercise stress testing is frequently limited by the patient's inability to exercise. Although pharmacologic stress testing with dobutamine is an alternative, the safety of dobutamine myocardial perfusion scintigraphy in the elderly has not been previously studied. PATIENTS AND METHODS: We studied the safety and feasibility of dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion scintigraphy using technetium single-photon emission CT imaging in 227 patients > or = 70 years old (mean +/- SD age, 75 +/- 4 years). A control group of 227 patients < 70 years old (mean age, 55 +/- 11 years; matched for gender, prevalence of previous infarction, beta-blocker therapy, and severity of resting perfusion abnormalities) was studied to assess age-related differences in the safety and the hemodynamic response. A feasible test was defined as the achievement of the target heart rate and/or an ischemic end point (angina, ST-segment depression, or reversible perfusion abnormalities). RESULTS: No myocardial infarction or death occurred during the test. The target heart rate was achieved more frequently in the elderly patients (87% vs 79%; p < 0.05). The elderly patients had a higher prevalence of supraventricular tachycardia (7% vs 1%; p < 0.005) and premature ventricular contraction (74% vs 32%; p < 0.005) during the test, as compared to the younger patients. There was a trend to a higher prevalence of ventricular tachycardia (5% vs 2%) and atrial fibrillation (3% vs 0.4%) in the elderly patients. Arrhythmias were terminated spontaneously by termination of dobutamine infusion or by administration of metoprolol. Independent predictors of supraventricular tachyarrhythmias and ventricular tachycardia were older age (p < 0.001; chi(2), 9.8) and myocardial perfusion defect score at rest (p < 0.01; chi(2), 6.8) resp

Objective. Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population. Methods. Patients with active RA diagnosed at age ≥ 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years. Results. During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group. Conclusion. Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.