Predictive role of positron emission tomography (PET) in the outcome of lymphoma patients.

An extensive analysis of the reliability of positron emission tomography (PET) after induction treatment in patients with Hodgkin's disease (HD) or aggressive non-Hodgkin's lymphoma (NHL). In all, 75 untreated patients with HD (n=41) or aggressive NHL (n=34) were studied with both PET and CT scans following standard chemotherapy induction therapy (ABVD or MACOP-B) with/without radiotherapy. Histopathological analysis was performed when considered necessary. After treatment, four out of five (80%) patients who were PET(+)/CT(-) relapsed, as compared with zero out of 29 patients in the PET(-)/CT(-) subset. Among the 41 CT(+) patients, 10 out of 11 (91%) who were PET(+) relapsed, as compared with 0 out of 30 who were PET(-). The actuarial relapse-free survival (RFS) rates were 9 and 100% in the PET(+) and PET(-) subsets, respectively (P=0.00001). All five patients who were PET(+)/CT(-) underwent a lymph node biopsy: in four (80%) cases, persistent lymphoma and was confirmed at histopathological examination. Two HD patients who were PET(-)/CT(+) (with large residual masses in the mediastinum or lung) were submitted to biopsy, which in both cases revealed only fibrosis. In HD and aggressive NHL patients, PET positivity after induction treatment is highly predictive for the presence of residual disease, with significant differences being observable in terms of RFS. PET negativity at restaging strongly suggests the absence of active disease; histopathological verification is important in patients who show PET positivity.

Results and potential of somatostatin receptor imaging in gastroenteropancreatic tract tumours.

BACKGROUND: Somatostatin receptor imaging with 111In-pentetreotide is widely accepted as an essential step in the management of patients affected by neuroendocrine tumours of the gastro-entero-pancreatic tract. Many data are already available on the high sensitivity of this technique. METHODS: We present a review of the published data together with the results of a study involving 253 patients submitted to somatostatin receptor imaging in three Italian hospitals. The patients were divided into two groups treated with different acquisition and processing protocols. RESULTS: The overall sensitivity was as high as (169/176) 96% in both groups, while the specificity was higher in the group in which semi-quantitative evaluation of somatostatin receptor density was performed: (23/26) 88% vs (39/51) 76%. The use of this method is recommended to increase the specificity of 111In-pentetreotide imaging. CONCLUSIONS: Our results with somatostatin receptor imaging in neuroendocrine tumours of the gastro-entero-pancreatic tract demonstrate that all figures of merit are excellent when imaging is accurately performed and analysed by experienced operators.

Diagnostic role of gallium scanning in the management of lymphoma with mediastinal involvement.

BACKGROUND AND OBJECTIVE: Therapy of both Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) with mediastinal presentation at the time of diagnosis is frequently followed by radiological detection of residual masses. Computed tomography (CT) scanning is generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate single photon emission ((67)GaSPECT) can potentially differentiate residual active tumor tissue from fibrosis. DESIGN AND METHODS: Seventy-five patients with HD or aggressive NHL presenting mediastinal involvement (64% with a bulky mass) were studied with CT and (67)GaSPECT at the end of combined modality therapy (chemo- and radiation therapy). RESULTS: After treatment, 3/3 (100%) patients with positive (67)GaSPECT and negative CT scan relapsed while only 1/18 (6%) patients with both negative (67)GaSPECT and CT scan did so. At the same time, 54 patients had a positive restaging CT scan (abnormal mass < 10% of size of initial mass). Of these patients, 13 had a positive (67)GaSPECT, 10 of whom (77%) relapsed; 41 had a negative (67)GaSPECT of whom 5 (12%) relapsed. The 4-year actuarial relapse-free survival rate was 90% for those with negative scans compared with 23% for gallium-positive patients (p < 0.000000). INTERPRETATION AND CONCLUSIONS: In lymphoma patients with mediastinal involvement, (67)GaSPECT should be considered, at least in patients who are CT positive, the imaging technique of choice for monitoring and differentiating the nature of any residual masses.

Childhood obesity: results of a multicenter study of obesity treatment in Italy.

The prevalence of pediatric obesity is increasing and many patients are followed by specialized centers or private doctors. The aim of this study was to verify short- and medium term results of a therapeutic approach based on nutritional intervention in a large pediatric population: 1383 subjects (695 females, 688 males) aged 10.1 +/- 2.7 yr, followed in 11 pediatric departments in Italy. No difference was found between centers in age, height, weight, BMI and IBW. The drop-out rate after the first visit was 30.2% (58.1% IBW > 140%) in females and 34.2% (70.7% IBW > 140%) in males. After two years of follow-up only 9.7% of females and 6.4% of males remained on treatment. Of these patients only 7.3% of females and 6.4% of males had IBW < 120%. These data show that an approach based on nutritional intervention alone is not sufficient for long-term treatment of pediatric obesity. Only an approach started early and involving the family can produce permanent results.

[Idiopathic interstitial pneumonitis presenting with Wells grade III. Can imaging methods help predict further progression of disease?]. / Fibrosi polmonare idiopatica con grado III di Wells all'esordio. Possono le metodiche di diagnostica per immagini aiutare a predire la progressione ulteriore della malattia?

PURPOSE: Three different grades of idiopathic pulmonary fibrosis can be identified by HRCT pattern. Patients with predominant ground-glass opacity (grade I) usually improve after treatment and may have a better prognosis. The subjects with a predominant reticular pattern and honeycombing (grade III) have irreversible fibrosis and usually do not improve after immunosuppressive therapy. Nevertheless, these patients may worsen even in the absence of HRCT features of the so-called alveolitis. We investigated the predictive role of some noninvasive imaging methods (HRCT with visual score of disease extent; Gallium scintigraphy; DTPA scintigraphy) in patients with idiopathic fibrosis and a prevalent macroscopic fibrosis at HRCT study. MATERIAL AND METHODS: Fourteen former smokers with grade III idiopathic fibrosis were examined. None of the patients had been treated. They were all submitted to HRCT, lung function studies, Gallium and DTPA scintigraphy, both at presentation (T0) and follow-up sessions (T1: mean one year post-diagnosis). The HRCT extent of disease was evaluated by means of the visual score as the fraction of the total lung volume. The patients were divided into two groups, using a cut-off value of 50%. All the patients underwent a Gallium scintiscan (using a fixation index of 160 as cut-off) and a ventilatory scintigraphy with DTPA-aerosol, with radionuclide clearance assessment. The lung function tests considered were vital capacity (VC), arterial blood oxygen partial pressure (PaO2) and the diffusing lung capacity for carbon monoxide (DLCO). RESULTS: After one year of follow-up, the HRCT extent score increased (from 46.6% to 50%) and lung function worsened (VC from 66.8% to 63.4% of predicted; DLCO from 37.6% to 27.1%; PaO2 from 77 to 71 mmHg). The patients presenting with HRCT extension score > 50% had a worse lung function at T0 and showed a significant deterioration of PaO2 and HRCT at T1. On the other hand, VC and DLCO significantly worsened in the subjects with HRCT score < 50% at presentation. The patients with a Gallium fixation index > 160 significantly deteriorated in HRCT score, VC and DLCO. Those with Gallium index < 160 had major worsening only for diffusing lung capacity for carbon monoxide. Thirteen of 14 patients had an abnormal value of DTPA clearance at presentation. No variation was observed at T1. DISCUSSION AND CONCLUSIONS: The majority of patients with idiopathic fibrosis are grade III at presentation. They can further deteriorate both in HRCT extent of disease and lung function impairment. After one year of follow-up HRCT extent score increased in 64% of the patients, with a mean increase of 5%. HRCT worsening was more apparent in the patients with a HRCT score > 50% at presentation. In the remaining patients, the worsening of lung function tests was more apparent than the anatomoradiological changes. DTPA clearance had no predictive value in this series. Gallium scintigraphy was a useful prognostic index. The patients with Gallium fixation index > 160 had better lung function and lower HRCT extent score at T0 but significantly deteriorated at T1. A positive Gallium scan at presentation could be considered a useful index of persisting active "alveolitis" in patients with grade III disease, not visible at HRCT study, due to overwhelming fibrosis. These patients, who were untreated, exhibit quicker radiological and functional worsening.

Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours.

Neuroendocrine tumours displaying somatostatin receptors have been successfully visualised with somatostatin receptor imaging (SRI). However, there may be differences in sensitivity depending on the site of the primary tumour and/or its metastases. We studied 131 patients affected by neuroendocrine tumours of the gastro-entero-pancreatic (GEP) tract. A pathological diagnosis was obtained in 116 patients, while in 15 the diagnosis was based on instrumental results and follow-up. Fifty-one patients were examined for staging purposes, 80 were in follow-up. Images were acquired 24 and 48 h after the injection of 150-220 MBq of indium-111 pentetreotide. Whole-body and SPET images were obtained in all patients. Patients were also studied with computed tomography (CT), ultrasound (US), and other procedures. Tumours were classified according to their site of origin: pancreas n = 39, ileum n = 32, stomach n = 16, appendix n = 9, duodenum n = 5, jejunum n = 5, rectum n = 3, biliary tract n = 2, colon n = 2, caecum n = 1, liver metastases from unknown primary = 15, widespread metastases from unknown primary = 2. Sensitivity for primary tumour localisation was as follows: SRI = 62%; CT = 43%; US = 36%; other procedures = 45%. Sensitivity for liver metastases: SRI = 90%; CT = 78%; US = 88%; other procedures = 71%. Sensitivity for the detection of extrahepatic soft tissue lesions was: SRI = 90%; CT = 66%; US = 47%; other procedures = 61%. Sensitivity for the detection of the primary tumour in patients with metastases from unknown primary sites: SRI 4/17; CT 0/13; US 0/12; other procedures 1/10. In 28% of the patients SRI revealed previously unknown lesions, and in 21% it determined a modification of the scheduled therapy. Our study confirms the important role of SRI in the management of GEP tumours. However, we feel that a critical investigation should address its role in locating primary tumours, in particular in patients with metastases from unknown primary sites.

Reproducibility of a solid and of a liquid caloric meal for gastric emptying studies.

Simple meals are required for routine scintigraphic gastric emptying studies. We evaluated the reproducibility of a caloric liquid meal (520 kcal) compared to that of a solid meal (638 kcal) in 8 and 11 healthy volunteers, respectively. Gastric emptying rates and half-times were similar in two tests using the same meal, while the methods used to express lag times were not highly reproducible. The emptying rates and half-times of the liquid meal were delayed after the intake of bellafoline. In conclusion, this study demonstrates that: (a) gastric emptying rates and half-times are reproducible parameters for the expression of scintigraphic gastric emptying studies; (b) mathematical methods to express lag times are not highly reproducible; (c) a 500 kcal liquid meal is sensitive to the effects of bellafoline, a drug able to delay gastric emptying. Further clinical evaluation is required to test its applicability in routine studies.

Relationship between plasma endothelin-1 levels and myocardial ischemia induced by exercise testing.

At peak exercise, plasma endothelin-1 concentration increases in patients with effort angina as well as thallium-201 radionuclide perfusion defects; the opposite occurs in patients with normal scans and in healthy volunteers. It is concluded that exercise-induced ischemia correlates with enhanced endothelin-1 production.

[Scintigraphy with radiogallium in oncologic and non-oncologic diseases. State of the art and main indications]. / La scintigrafia con radiogallio nelle malattie oncologiche e non oncologiche. Stato dell'arte e principali indicazioni.

Gallium-67 citrate (67Ga) can be considered one of the most widespread viability radiotracers. Several papers have recently been published on the use of 67Ga in different diseases, with emphasis on its value in the management of lymphoma patients. This paper critically discusses the role of gallium scintigraphy in several diseases on the basis of our personal experience and of the latest literature data, to integrate the diagnostic knowledge of radiologists, oncologists, nuclear medicine and laboratory physicians. From a clinical point of view, the best application is in neoplastic diseases, particularly lymphoma, but also in inflammatory conditions. Gallium scan sensitivity is very high (80-90%) in the staging and follow-up of Hodgkin's and non-Hodgkin's lymphoma and this method is also of great importance during the follow-up of lymphoma patients. We recommend scintigraphy to study the residual mediastinal mass after treatment. The recent experience of the National Cancer Institute (Milan) in the follow-up of 189 lymphoma patient showed the major role of gallium scan, compared with MRI, in the study of the mediastinal region after treatment. Both sensitivity and specificity were very high (90 and 96.9% vs 88.7 and 89.2% respectively). Gallium scintigraphy can also be used to study the disease-free interval, post-treatment survival, the early signs of a recurrence and also of treatment response times. The comparison of the survival curves of 33 diffuse large cell non-Hodgkin's lymphoma patients, examined at the National Cancer Institute, showed a statistically significant difference (log-rank test: p = 0.0125) between patients with positive and negative gallium scan after 4-6 cycles of chemotherapy. As for inflammatory diseases, gallium scintigraphy can play a major diagnostic role in pulmonary conditions, e.g., sarcoidosis, in AIDS-related respiratory diseases, in pneumoconiosis and in some cases of "fever of unknown origin". The contribution of this technique consists in localizing an infection focus and assessing the inflammatory disease activity, thus permitting a better therapeutic approach.

Dynamic planar myocardial perfusion imaging in patients with one-vessel disease with intracoronary injection of technetium 99m teboroxime during papaverine-induced coronary hyperemia.

This study examined the imaging results and kinetics of technetium 99m teboroxime after its intracoronary injection during papaverine-induced coronary hyperemia in patients with one-vessel disease before and after coronary angioplasty. Thirteen patients with > or = 90% diameter stenosis of either the left anterior descending or the left circumflex coronary artery were included. Two patients were excluded because of ventricular tachycardia during papaverine injection in one patient and unsuccessful angioplasty in the second patient. One mCi of technetium 99m teboroxime was injected into the left main coronary artery during coronary hyperemia induced by intracoronary injection of papaverine. Dynamic acquisition in a frame mode (20 sec/frame) was performed for 5 minutes in the left anterior oblique projection with a multicrystal gamma camera before and after successful angioplasty. Ischemic:normal count ratio increased from 0.75 +/- 0.4 before to 1.00 +/- 0.50 after angioplasty (p < 0.1). The T 1/2 of teboroxime was 6.5 +/- 1.5 min in the normal zone and 7.2 +/- 1.9 min in the ischemic zone (p, NS). Perfusion defects were visible in the territory of the stenosed coronary artery in 9 of 11 patients before angioplasty and in 7 of 11 patients after angioplasty. The image quality was excellent in all studies. Thus this study shows that performing dynamic imaging with intracoronary injection of technetium 99m teboroxime is feasible. This technique may be useful to study the impact of angioplasty on coronary flow and tracer kinetics.

Bartter's syndrome: renal scintigraphic appearance after captopril administration.

We report a case of Bartter's syndrome, a rare disease characterized by hypokalemia, increased plasma renin and angiotensin II levels with normal blood pressure. During the diagnostic work-up, the patient had renal scintigraphy in baseline and after captopril administration. Pharmacological blockade of the renin-angiotensin system with captopril resulted in bilateral and symmetrical renal abnormalities (increase of parenchymal transit time, time to maximum activity and retained cortical activity, with cortical trapping of the radiopharmaceutical). Baseline scintigraphy was normal. The findings are consistent with Bartter's syndrome pathogenesis. Captopril renography may be useful to differentiate Bartter's syndrome from other covert causes of hypokalemia.

Monitoring bulky mediastinal disease with gallium-67, CT-scan and magnetic resonance imaging in Hodgkin's disease and high-grade non-Hodgkin's lymphoma.

Treatment of both Hodgkin's disease (HD) and high-grade non-Hodgkin's lymphoma (HG-NHL) with bulky presentation at diagnosis frequently results in residual masses detected radiologically. Conventional diagnostic radiology and computed tomography (CT) are generally unable to detect the differences between tumor tissue and fibrosis. Gallium-67-citrate (67Ga) SPECT and magnetic resonance imaging (MRI) can potentially differentiate residual active tumor tissue and fibrosis. Thirty-three patients with HD or HG-NHL presenting with bulky mediastinal disease were studied with CT, 67Ga SPECT, and MRI (only for 16 patients) at diagnosis, after two-thirds of their chemotherapy, at the end of chemotherapy, and after radiotherapy in order to evaluate the mediastinal region on the basis of persistence of residual masses and activity of pathological tissue. After treatment, all patients with 67Ga-negative (30/33) disease are still in continuous complete response. Among the three 67Ga-positive patients, 2 relapsed within one year and another one is still alive without evidence of disease. Regarding MRI, two patients were found to be positive, one of them concomitant with 67Ga-positivity; both patients survive in complete response. In lymphoma patients with bulky mediastinal presentation, the 67Ga SPECT remains the preferable imaging technique for monitoring and differentiating the eventual active residual tumor. In combination, CT and 67Ga SPECT represent a suitable complete imaging approach to the radiological diagnosis which may be useful in these particular patients. MRI could probably be considered as a second-line method and from our data would be used only in selected cases because of the high cost, accessibility, and lower specificity as opposed to 67Ga SPECT in evaluating potentially active residual disease.

Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia.

BACKGROUND & AIMS: Although gastric dysmotility and dyspeptic symptoms are often associated, their relationship remains unclear. The aim of this study was to evaluate the relationship between gastric emptying abnormalities and clinical features in functional dyspepsia. METHODS: In 343 patients with functional dyspepsia, the gastric emptying of solids was measured by a radioisotopic technique and four dyspeptic symptoms (epigastric pain and burning, postprandial fullness, nausea, and vomiting) were measured as absent, mild, relevant, and severe, according to their influence on patients' usual activities. RESULTS: Delayed gastric emptying was detected in 33.5% of dyspeptics. Delayed gastric emptying was particularly frequent in patients characterized by female sex, low body weight, presence of relevant and severe postprandial fullness, nausea, vomiting, and absence of relevant and severe epigastric pain. Logistic regression showed that delayed gastric emptying was invariably associated with female sex and postprandial fullness (odds ratio, 2.34; 95% confidence interval, 1.45-3.75) and vomiting (odds ratio, 4.04; 95% confidence interval, 1.30-12.54) when coded as severe and only postprandial fullness (odds ratio, 3.78; 95% confidence interval, 1.78-8.01) when coded as relevant and severe. CONCLUSIONS: Female sex, relevant and severe postprandial fullness, and severe vomiting are independently associated with delayed gastric emptying of solids in patients with functional dyspepsia seen in a referral center.

Gastric emptying of solids in morbid obesity.

OBJECTIVE: To evaluate the effect of weight loss induced by dietetic treatment, with or without an intragastric balloon, on gastric emptying of obese subjects. SUBJECTS: 20 morbidly obese subjects (21-54 years, 45.3-58.0 kg/m2) and 20 healthy controls (21-56 years, 20.3-24.8 kg/m2). DESIGN: Parallel study of a 4 month, low calorie dietetic treatment with or without a 500 ml intragastric balloon. RESULTS: In basal conditions, obese subjects had accelerated gastric emptying as compared to healthy controls. At the end of the dietetic treatment period, a significant decrease of body weight was obtained. Patients also showed a slowing of gastric emptying. Both the weight loss and the slowing of gastric emptying occurred irrespective of the presence or absence of the intragastric balloon. CONCLUSION: The present findings are compatible with the hypothesis that gastric emptying, food intake and body weight are integrated parameters in subjects with morbid obesity.

Evaluation of lung clearance of inhaled pertechnegas.

Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

[Bulky mediastinal lymphomas: role of magnetic resonance and SPECT-Ga-67 in the evaluation of residual masses]. / I linfomi "bulky" con localizzazione mediastinica: ruolo della risonanza magnetica e della SPET-Ga67 nella valutazione delle masse residue.

A residual mediastinal mass is a common finding during and/or after treatment for bulky mediastinal lymphoma and represents a difficult diagnostic problem. For correct therapy modulation, fibrosis must be distinguished from active disease. To assess diagnostic imaging potentials in the characterization of residual masses, 41 patients with bulky mediastinal lymphoma were examined with CT, MRI and Ga67-SPET; 92 examinations were performed for each technique: 14 before treatment, 42 during and after chemotherapy, 13 after radiotherapy and 23 six months after the end of treatment. CT provides useful pieces of information on tumor size but fails to depict tissue changes: therefore, only MR and SPET results were considered and compared with clinico-biological and follow-up findings. MRI and SPET were often in agreement with each other (78/92 cases) and with clinical data (98.7%); each examination yielded only one false positive. In case of disagreement (14/92 patients), MRI yielded more false-positive findings because it failed to differentiate neoplastic tissue from treatment-related conditions, i.e., granulation tissue, inflammation, necrosis, early fibrosis. In contrast, negative MR results were more reliable, MR negative predictive value being 100%. Ga67-SPET exhibited high sensitivity (97.1%) and specificity (91.2%), with fewer false positives than MRI (5 vs. 10). In conclusion, both examinations were accurate in the characterization of residual mediastinal masses during and after therapy, but MRI had higher sensitivity and Ga67-SPET higher specificity. Therefore, the authors acknowledge the complementary role of these two techniques and the necessity of an integrated approach, i.e., combined MRI and Ga67-SPET or CT and Ga67-SPET.