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M Schwaiger

Publications and source records attributed to M Schwaiger.

At least 55 records · Page 3Linked to original sources

Neurotransmitter changes by interferon-alpha and therapeutic implications.

Interferon alpha (IFN-alpha) is a cytokine that is widely used for the treatment of chronic viral infection or malignant disorders. During treatment with IFN-alpha, severe neuropsychiatric syndromes may occur such as depression with suicidal ideation, paranoid psychoses or confusional states. The neurobiological correlates of these side effects are widely unknown. Besides induction of other cytokines and hormonal changes, IFN-alpha has been shown to modulate the opioid, serotonin, dopamine and glutamate neurotransmitter system. Positive therapeutic effects of antidepressants such as selective serotonin-reuptake-inhibitors (SSRI) or of opioid receptor antagonists support the hypothesis that neurotransmitter changes play an important role in the development of IFN-alpha associated neuropsychiatric side effects. We review recent research about IFN-associated neurotransmitter changes in the central nervous system and discuss treatment strategies.

Animals↗

Alterations of myocardial presynaptic sympathetic innervation in patients with multi-vessel coronary artery disease but without history of myocardial infarction.

In patients with myocardial infarction, left ventricular sympathetic denervation exceeds the size of the scar tissue. However, little is known about the regional innervation in patients with coronary artery disease (CAD) but no myocardial infarction. Using positron emission tomography (PET) with N-ammonia and C-hydroxyephedrine (HED), resting perfusion and presynaptic sympathetic innervation were studied in eight patients (seven males, one female; 58+/-9 years) with multi-vessel CAD and no history of myocardial infarction. Using polar map analysis of the PET data, the results were regionally compared with normal databases. The mean HED retention was 8.0%+/-2.0% x min(-1). Myocardial resting perfusion was normal in 23 of 24 vascular territories. Despite normal resting perfusion, significantly reduced HED retention, indicating dysinnervation, was found in 14 of 23 (61%) vascular territories (six of eight patients). Of the dysinnervated territories, 11 (79%) showed angiographically severe stenosis (>or=90% of native vessel/coronary artery bypass graft), eight (57%) showed ischaemia (myocardial perfusion scintigraphy/stress-electrocardiogram) and 12 (86%) had been revascularized. Of the nine segments with normal innervation, two (22%) revealed severe stenosis, two (22%) showed ischaemia and seven (78%) had been revascularized. It can be concluded that, in patients with advanced CAD and normal left ventricular function, dysinnervation can occur in the absence of myocardial infarction. This is consistent with the hypothesis that sympathetic neurones are more susceptible than myocytes to ischaemic damage.

Aged↗

Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries.

OBJECTIVES: To investigate myocardial blood flow of the morphological right systemic ventricle in unoperated patients with congenitally corrected transposition of the great arteries (CCTGA) by positron emission tomography (PET). DESIGN: Prospective cross sectional clinical study. SETTING: Tertiary referral centre for paediatric cardiology. PATIENTS: 15 patients with CCTGA were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilatation. A subgroup of seven patients had isolated CCTGA (group A, mean (SD) age 30.3 (11.9) years) and the remaining eight patients had complex CCTGA associated with subpulmonary stenosis; four of this second group also had ventricular septal defect (group B, mean (SD) age 30.6 (16.4) years). Eleven healthy adults (mean (SD) age 26.2 (5.1) years) served as the control group. RESULTS: Resting myocardial blood flow was not different between both groups of patients with CCTGA and the controls. Hyperaemic blood flows were significantly lower in both groups of CCTGA than in the control group (mean (SD) 195 (21) ml/100g/min in group A, 201 (27) ml/100g/min in group B, 309 (74) ml/100g/min in the control group; p < 0.001). Thus, coronary flow reserve was significantly lower in both groups of CCTGA than in the control group (mean (SD) 2.5 (0.28) in group A, 2.6 (0.48) in group B, and 4.0 (0.73) in the control group; p < 0.001). CONCLUSION: Blood flow measurements suggest that coronary reserve is decreased in the absence of ischaemic symptoms in patients with CCTGA. The global impairment of stress flow dynamics may indicate altered global vasoreactivity, and quantitative changes in microcirculation suggest that their role in the pathogenesis of systemic right ventricular dysfunction is important.

Adenosine↗

Radiotracer-based strategies to image angiogenesis.

Tumour-induced angiogenesis plays an important role in tumour progression. Great efforts are made to develop therapeutic strategies to interfere with this process resulting in the starvation of the tumour. However, strategies to monitor conventional therapies seems to be inappropriate to control these approaches. Thus, there is a keen interest in developing methods supplying information about the corresponding therapeutical effects. Several radiotracer-based approaches focused on different targets in the angiogenic process are currently investigated. One class of tracers is based on matrix metalloproteinases inhibitors. These compounds show promising results in in vitro assays. However, initial data from in vivo studies using murine tumour models could not confirm successful non-invasive monitoring of MMP activity yet. Another strategy uses a radiolabelled single chain fragment against the ED-B domain of fibronectin, an extracellular matrix protein. Promising results demonstrated selective accumulation of the tracer in the tumour vasculature of a murine tumour model. Most of the studies are concentrated on the development of radiolabelled antagonists of the integrin alpha(v)beta(3). This heterodimeric transmembrane glycoprotein is involved in the migration of activated endothelial cells during formation of new vessels. Different compounds have been labelled with (18F), (111)In, (99m)Tc, (90)Y and several iodine isotopes. In in vitro assays most of them revealed high alpha(v)beta(3) affinity and selectivity. Moreover, in different murine tumour models successful non-invasive determination of alpha(v)beta(3) expression has been shown. Some of these approaches indicate that tumour-induced angiogenesis can be monitored in animal studies. Nevertheless, translation of these approaches into clinical settings allowing visualisation of tumour-induced angiogenesis in patients needs still to be demonstrated.

Animals↗

[PET with (18)F-fluorodeoxyglucose for staging of non-small cell lung cancer].

AIMS: To evaluate studies on the use of positron emission tomography with the glucose analog (18)F-fluoro-deoxyglucose (FDG-PET) for the preoperative staging of patients with non-small cell lung cancer (NSCLC) according to the criteria of evidence based medicine and to discuss the cost-effectiveness of the technique. METHODS: Clinical studies published between 1995 and 2002 on the preoperative staging of non-small cell lung cancer were used for this analysis. Studies that did not meet the criteria published by the European Agency for the Evaluation of Medicinal Products (EMEA) were excluded. The validity of the studies was evaluated by a standardized rating system developed by the Agency for Health Care Policy and Research (AHCPR). RESULTS: For the detection of mediastinal lymph node metastases the mean sensitivity and specificity of FDG-PET on a patient basis is 85% and 87% (16 studies, 1355 patients). In studies that compared FDG-PET and computed tomography (CT) the mean sensitivity of CT was 66% at a specificity of 71%. In the detection of distant metastases FDG-PET correctly changed the tumor stage in 18% of the patients when compared to CT based staging (10 studies, 1073 patients). Five cost effectiveness analyses from the USA, Japan, and Germany concluded that FDG-PET improves the outcome of treatment at reduced or only slightly increased overall costs. Improvement of patient outcome was also demonstrated in a randomized trial, which found that the risk of a futile thoracotomy was reduced by 51% (p=0.003) when FDG-PET was added to the preoperative staging. CONCLUSION: According to the criteria of the AHCPR the use of FDG-PET for detection of mediastinal lymph node and distant metastases is documented at a level of evidence Ia and Ib, respectively. Since systematic analyses also indicate a favorable cost-effectiveness ratio FDG-PET has to be considered as "strictly indicated" for the preoperative staging of non-small cell lung cancer.

Carcinoma, Non-Small-Cell Lung↗

[18F-Fluorodeoxyglucose positron emission tomography in restaging of colorectal cancer].

UNLABELLED: AIM, METHOD: Recommendations for the use of FDG-PET in relapsed colorectal cancer and the decision of reimbursement should base on published studies and on their level of evidence. Therefore, the PET-studies published between 1997 and 2002 were graded by the bias-criteria, by two rating-systems and by two classification-systems for the level of evidence according to AHCPR (Agency for Health Care Policy and Research) and VHA (Veterans Health Administration). RESULTS: The recommendation for the use of PET in relapsed colorectal cancer reached the level IIa according to the AHCPR, corresponding to level B according to the VHA. The sensitivity and specificity of FDG-PET were 94% (95% CI: 91-96%) and 78% (95% CI: 69-86%), respectively. Staging was changed correctly in 27% of patients (95% CI: 24-30%). Staging by FDG-PET was incorrect in 4% of the patients (95% CI: 2-5%) compared with the conventional methods. The additional use of PET changed the prospectively defined management plan for 34% of patients (95% CI: 31-38%). Either potentially curative operations were initiated in case of resectable tumour or futile operations were cancelled in case of multiple metastases. CONCLUSION: The 3-year-survival-rate following surgery would have exceeded 70% if the selection of patients had included an additional PET-examination. The correct selection of patients is requested in the daily routine as well as in the clinical implementation of neoadjuvant therapies to prevent a selection-bias from a suboptimal restaging without PET.

Colorectal Neoplasms↗

PET imaging of somatostatin receptors: design, synthesis and preclinical evaluation of a novel 18F-labelled, carbohydrated analogue of octreotide.

Because of the excellent nuclear properties of fluorine-18 and the growing interest in somatostatin receptor (sst) scintigraphy with PET, a novel carbohydrated (18)F-labelled sst ligand was developed and preclinically evaluated. Synthesis of N(alpha)-(1-deoxy- D-fructosyl)- N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate ([(18)F]FP-Gluc-TOCA) was completed in approximately 3 h (20%-30% yield). [(19)F]FP-Gluc-TOCA showed no affinity to hsst1 and hsst3, moderate affinity to hsst4 (IC(50): 437+/-84 n M) and hsst5 (IC(50): 123+/-8.8 n M) and very high affinity to hsst2 (IC(50): 2.8+/-0.4 n M). As a result of carbohydration, lipophilicity of [(18)F]FP-Gluc-TOCA was found to be low (lg P(OW)=-1.70+/-0.02). In mice, the tracer was rapidly cleared via renal excretion (kidneys: 8.69%+/-1.09%ID/g) and showed low uptake in liver (0.72%+/-0.14%ID/g) and intestine (1.88%+/-0.52%ID/g) and high tumour uptake (13.54%+/-1.47%ID/g) (all data at 1 h p.i.). Tumour to non-tumour ratios at 60 min p.i. reached 25, 19, 7, 1.6 and 56 for blood, liver, intestine, kidney and muscle, respectively. A similar biodistribution pattern was observed in pancreatic tumour-bearing rats. Tumour uptake in rats was reduced to 36% and 18% of control (30 and 60 min) by co-injection of 500 microg Tyr(3)-octreotide, demonstrating sst-specific uptake. In a first [(18)F]FP-Gluc-TOCA-PET study of a patient with a metastatic carcinoid in the liver the tracer showed superior pharmacokinetics, e.g. rapid urinary excretion and low uptake in liver, kidney and spleen. Multiple liver lesions (SUVs ranging from 21.4 to 38.0) and previously unknown focal uptake in the abdomen (SUV 10.0) were clearly visible. This is the first report on PET imaging using an (18)F-labelled sst binding peptide; it indicates that [(18)F]FP-Gluc-TOCA offers excellent imaging characteristics and allows sst imaging with high tumour to non-tumour contrast.

Aged↗

Monitoring of tumour glucose metabolism by PET in a phase I study evaluating hormonal therapy in advanced pancreatic cancer.

BACKGROUND: Positron emission tomography (PET) determines therapy-induced changes in tumour glucose utilization. Experimental data indicate that cholecystokinin (CCK) stimulates pancreatic cancer growth. In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B). METHODS: Nineteen patients were enrolled on a 28-day course of SR 27897B. Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and 6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at baseline and on days 14 and 28. RESULTS: No significant changes in FDG uptake by the primary tumours were observed. Rate of progression of disease was 11 (61%) of 18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7 months. SR 27897B was fairly well tolerated at all doses tested. The most common side effects were gastrointestinal disorders such as diarrhoea, flatulence and nausea. CONCLUSION: SR 27897B, when used alone at the limited doses employed, led neither to an impairment of tumour glucose metabolism nor to a reduction of tumour size in advanced pancreatic cancer.

Adenocarcinoma↗

A scintigraphic study of local oesophageal bolus transit: differences between patients with Barrett's oesophagus and healthy controls.

BACKGROUND: In Barrett's patients, functional disorders of oesophageal motility are currently measured by oesophageal manometry. Yet abnormalities of oesophageal volume transport in the critical regions of the upper oesophageal sphincter (UOS) and lower oesophageal sphincter (LOS) cannot be determined using these methods. AIMS: To further characterise the activity of the sphincter regions, we developed a quantitative method for differentiation of oesophageal volume transport in Barrett's patients and healthy controls. METHODS: We used a new technique of processing scintigraphic images, with data analysis based on a new concept of relative local transit time. Twelve patients with Barrett's oesophagus and 11 healthy volunteers were examined using alimentary scintigraphy after a semisolid test meal in a multiple swallow test. In individual scintigraphic images of five swallows we studied: (1) overall oesophageal clearance and (2) the topographic profile of the relative local transit time obtained by image conversion to a two dimensional line graph. This profile was reconstructed by assembling constituent Gauss bands, allocating their integrals to five oesophageal regions according to their band position. RESULTS: (1) Overall oesophageal clearance was not significantly different between the two groups. (2) In comparison with healthy volunteers, relative regional transit times of all 12 Barrett's patients were significantly increased in the hypopharyngeal region and decreased in the region of the distal oesophagus. The extent of the decrease in the region of the distal oesophagus showed a close correlation with the length of Barrett's metaplasia. CONCLUSION: Improvement in image processing allows alimentary scintigraphy to describe different regional patterns of oesophageal volume transport. Local oesophageal bolus transit is markedly abnormal in Barrett's patients without alteration in clearance. The presence of metaplasia itself implies a negative impact on both sphincter functions. These findings substantiate the diagnostic value of refined oesophageal scintigraphy.

Adult↗

Prediction of left ventricular functional recovery by dobutamine echocardiography, F-18 deoxyglucose or 99mTc sestamibi nuclear imaging in patients with chronic myocardial infarction.

BACKGROUND: Currently, several modalities are available to predict viability, however, studies comparing various modalities validated by functional recovery after revascularization are scarce. This study analyzed the relative merits of low-dose dobutamine echocardiography, F-18 deoxyglucose (FDG) positron emission tomography (PET) and (99m)Tc sestamibi single-photon emission computed tomography to predict functional recovery after revascularization in patients with chronic myocardial infarction. METHODS: Patients with chronic coronary occlusion (duration: 3.1 +/- 4.8 years) and impaired left ventricular function (ejection fraction: 42 +/- 13%) underwent low-dose dobutamine echocardiography (20 microg/kg/min), FDG-PET and (99m)Tc sestamibi imaging before revascularization. Revascularization was performed irrespective of any viability data. Follow-up angiography was obtained 4.8 +/- 2.5 months after revascularization. RESULTS: Viability analysis was performed in 34 patients with patent target vessel at follow-up, of whom 9 (27%) exhibited functional recovery on left ventricular angiography. For dobutamine echocardiography, improvement of >/=2 adjacent akinetic segments resulted in improved sensitivity of 89% and specificity of 80% to predict functional recovery. For glucose metabolism, FDG uptake >55% was an optimal threshold yielding a sensitivity of 89% and a specificity of 68%. With respect to perfusion, (99m)Tc sestamibi uptake >60% was the best cutoff resulting in a sensitivity and a specificity of 56 and 88%, respectively. A concordant match of FDG >55% and of (99m)Tc sestamibi >50% resulted in optimized sensitivity (78%) and specificity (80%) with dual imaging. CONCLUSIONS: Recovery of chronically dysfunctional myocardium can be predicted with high accuracy by stimulation of contractile reserve or by concordant match of preserved glucose metabolism and residual perfusion.

Aged↗

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction.

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.

Adult↗

Excretion of FDG into saliva and its significance for PET imaging.

AIM: Assessment of the salivary excretion of FDG and its significance during PET imaging. METHODS: Salivary samples from 16 patients were obtained during the first three hours after FDG injection and their activity concentrations were measured. Furthermore, regional FDG accumulations in whole body PET scans (60 min p.i., ROI technique) were determined in the following locations: vestibulum oris, floor of the mouth, hypopharynx, parotid gland, submandibular gland. This ROI analysis was repeated after drinking water (0.2 l) and a second scan (120 min p.i.). RESULTS: The salivary FDG concentrations (SUV) at the first, second and third hour p.i. were 0.2 +/- 0.1, 0.4 +/- 0.2, and 0.3 +/- 0.2, respectively. The FDG uptake in the investigated cranial and cervical sites ranged from SUV 1.2 +/- 0.5 in the major salivary glands to 2.1 +/- 0.5 in the floor of the mouth. These values remained unchanged after drinking of water. CONCLUSION: The salivary FDG concentration is higher than expected from the low physiologic content of glucose. This may--similarly to renal excretion--reflect a different behavior of FDG and glucose during reabsorption processes. Nevertheless, the salivary concentration of FDG is so low that no relevant influence on PET imaging is to be expected. Accordingly, the drinking of water prior to the scan is of no benefit for FDG PET imaging of the head and the neck.

Fluorodeoxyglucose F18↗

PET in patients with clear-cut multiple chemical sensitivity (MCS).

AIM: Multiple chemical sensitivity (MCS) is a controversially discussed symptom complex. Patients afflicted by MCS react to very low and generally non-toxic concentrations of environmental chemicals. It has been suggested that MCS leads to neurotoxic damage or neuroimmunological alteration in the brain detectable by position emission tomography (PET) and single photon emission computer tomography (SPECT). These methods are often applied to MCS patients for diagnosis, although they never proved appropriate. METHOD: We scanned 12 MCS patients with PET, hypothesizing that it would reveal abnormal findings. RESULTS: Mild glucose hypometabolism was present in one patient. In comparison with normal controls, the patient group showed no significant functional brain changes. CONCLUSION: This first systematic PET study in MCS patients revealed no hint of neurotoxic or neuroimmunological brain changes of functional significance.

Adult↗

NMR spectroscopy reveals the solution dimerization interface of p53 core domains bound to their consensus DNA.

The p53 protein is a transcription factor that acts as the major tumor suppressor in mammals. The core DNA-binding domain is mutated in about 50% of all human tumors. The crystal structure of the core domain in complex with DNA illustrated how a single core domain specifically interacts with its DNA consensus site and how it is inactivated by mutation. However, no structural information for the tetrameric full-length p53-DNA complex is available. Here, we present novel experimental insight into the dimerization of two p53 core domains upon cooperative binding to consensus DNA in solution obtained by NMR. The NMR data show that the p53 core domain itself does not appear to undergo major conformational changes upon addition of DNA and elucidate the dimerization interface between two DNA-bound core domains, which includes the short H1 helix. A NMR-based model for the dimeric p53 core-DNA complex incorporates these data and allows the conclusion that the dimerization interface also forms the actual interface in the tetrameric p53-DNA complex. The significance of this interface is further corroborated by the finding that hot spot mutations map to the H1 helix, and by the binding of the putative p53 inhibitor 53BP2 to this region via one of its ankyrin repeats. Based on symmetry considerations it is proposed that tetrameric p53 might link non-contiguous DNA consensus sites in a sandwich-like manner generating DNA loops as observed for transcriptionally active p53 complexes.

Amino Acid Sequence↗

Effect of sympathetic reinnervation on cardiac performance after heart transplantation.

BACKGROUND: Late after cardiac transplantation, limited reinnervation of the transplanted heart may occur, but little is known about the effect of reinnervation on cardiac function and exercise performance. METHODS: We quantified the extent of myocardial reinnervation noninvasively in 29 cardiac-transplant recipients, using positron-emission tomography and the catecholamine analogue [11C]hydroxyephedrine. Global and regional ventricular function at rest and during standardized exercise testing were measured with the use of radionuclide angiography, and the results were compared with those in 10 healthy controls. RESULTS: Sympathetic reinnervation, mainly in the anteroseptal wall, was present in 16 of the 29 transplant recipients. At rest, hemodynamic differences were not observed between the patients with reinnervation and those with denervation. However, the latter group had a shorter mean (+/-SD) exercise time (6.1+/-1.5, minutes vs. 8.2+/-1.2 in the group with reinnervation; P<0.01) and a lower peak heart rate (121+/-13 vs. 143+/-15 beats per minute, P<0.01). The contractile response to exercise was significantly enchanced in transplant recipients with reinnervation and similar to that of normal controls. In a multivariate analysis, hydroxyephedrine retention was the only independent determinant of the exercise-induced increase in the ejection fraction. CONCLUSIONS: In heart-transplant recipients, the restoration of sympathetic innervation is associated with improved responses of the heart rate and contractile function to exercise. These results support the functional importance of reinnervation in transplanted hearts.

Carbon Radioisotopes↗

Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging.

PURPOSE: Preoperative chemotherapy in patients with gastroesophageal cancer is hampered by the lack of reliable predictors of tumor response. This study evaluates whether positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) may predict response early in the course of therapy. PATIENTS AND METHODS: Forty consecutive patients with locally advanced adenocarcinomas of the esophagogastric junction were studied by FDG-PET at baseline and 14 days after initiation of cisplatin-based polychemotherapy. Clinical response (reduction of tumor length and wall thickness by > 50%) was evaluated after 3 months of therapy using endoscopy and standard imaging techniques. Patients with potentially resectable tumors underwent surgery, and tumor regression was assessed histopathologically. RESULTS: The reduction of tumor FDG uptake (mean +/- 1 SD) after 14 days of therapy was significantly different between responding (-54% +/- 17%) and nonresponding tumors (-15% +/- 21%). Optimal differentiation was achieved by a cutoff value of 35% reduction of initial FDG uptake. Applying this cutoff value as a criterion for a metabolic response predicted clinical response with a sensitivity and specificity of 93% (14 of 15 patients) and 95% (21 of 22), respectively. Histopathologically complete or subtotal tumor regression was achieved in 53% (eight of 15) of the patients with a metabolic response but only in 5% (one of 22) of the patients without a metabolic response. Patients without a metabolic response were also characterized by significantly shorter time to progression/recurrence (P =.01) and shorter overall survival (P =.04). CONCLUSION: PET imaging may differentiate responding and nonresponding tumors early in the course of therapy. By avoiding ineffective and potentially harmful treatment, this may markedly facilitate the use of preoperative therapy, especially in patients with potentially resectable tumors.

Adenocarcinoma↗