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.

A case of metastatic medullary thyroid carcinoma: early identification before surgery of an RET proto-oncogene somatic mutation in fine-needle aspirate specimens.

Medullary thyroid carcinoma (MTC) management requires determination of the sporadic or familial nature of the disease. RET proto-oncogene mutation analysis in the tumor tissue obtained at surgery and in the peripheral blood identifies somatic vs. germinal mutations. We now report a case of MTC in which a RET somatic mutation at codon 918 was detected in fine-needle aspiration specimens obtained from both the thyroid nodule and two enlarged neck lymph nodes but not in peripheral blood. Therefore, a diagnosis of sporadic MTC was made before surgery. Thus, this approach, by excluding preoperatively multiple endocrine neoplasia disease, permitted immediate thyroidectomy without search for pheochromocytoma. PCR-based genetic analysis in fine-needle aspiration biopsy specimens, therefore, preoperatively identifies genetic abnormalities at an early and easily manageable stage and may well contribute to the management strategy of MTC.

CEA, MCA, CA 15.3 and CA 549 and their combinations in expressing and monitoring metastatic breast cancer: a prospective comparative study.

Serum levels of carcinoembryonic antigen (CEA), mucin-like carcinoma-associated antigen (MCA), CA 15.3 and CA 549 were concurrently assayed in patients with metastatic breast cancer. Overall sensitivity in detecting metastatic breast cancer (201 pts) was CEA 45%, MCA 59%, CA 15.3 71% and CA 549 72% (P < 0.01). Sensitivity increased by only 6% to 8% when two or more antigens were simultaneously considered. An overall sensitivity of correlation with objective response (n = 71) was observed in the range of 53-67% (P = n.s.) in patients with abnormal baseline marker values, and in the range of 42-87% (P < 0.05) in patients with normal baseline values. The combination of two or more markers did not improve sensitivity, but decreased specificity of correlation with objective response. In conclusion, CA 15.3 and CA 549 have individually higher sensitivity in detecting metastatic breast cancer. No clinical advantage was observed for using two or more markers concurrently over CA 15.3 or CA 549 alone in the monitoring of metastatic breast cancer.

Detecting hibernated myocardium with SPECT and thallium-glucose-insulin infusion.

UNLABELLED: Because thallium kinetics, like potassium kinetics, may be affected by serum insulin levels, we performed two pilot studies to identify severely ischemic myocardium using different protocols based on the infusion of a thallium, insulin, potassium and glucose solution. Results were compared with those obtained with two currently used protocols based on rest injection or reinjection of 201Tl. METHODS: In the first study (Protocol 1) of 15 men with a previous large myocardial infarction, perfusion was evaluated by SPECT in 20 segments after a 30-min infusion of 201Tl (111 MBq), insulin (5 U) and potassium (10 mEq) in 10% glucose solution (250 ml). Imaging was repeated 30 min later and the results were compared with those obtained from stress and 3-hr reinjection images. In the second study (Protocol 2), 15 patients were evaluated randomly at rest and 3 hr later (rest-redistribution). On a separate day, the patients were then re-evaluated after infusion of 201Tl (111 MBq), potassium (10 mEq) and insulin (5 U) in 5% glucose (250 ml); images were obtained 90 and 180 min postinjection. RESULTS: In Protocol 1, radiotracer activity in segments with no uptake during stress was detected in 35% with the reinjection technique and 58% with the insulin solution protocol. In Protocol 2, 31% of segments revealed thallium activity after insulin infusion but not at rest or rest-redistribution. Serum measurements showed high insulin levels (444 +/- 138 in Protocol 1, 125 +/- 33 mU/ml in Protocol 2), although glucose levels were not significantly altered (149 +/- 32 versus 71 +/- 20 mg/dl, respectively). Potassemia was not affected and the patients tolerated the tests satisfactorily. CONCLUSION: These results confirm that continuous infusion of 201Tl with a low dose of insulin in a glucose/potassium chloride solution is safe and may enhance cellular uptake of the radiotracer in severe ischemic regions, thereby improving viable myocardium detection.

Evaluation of hypertensive patients with a solitary kidney using captopril renal scintigraphy with 99Tcm-MAG3.

The study aimed to evaluate the safety and reliability of captopril renal scintigraphy (CRS) for diagnosing functionally significant renal artery stenosis (RAS) in hypertensive patients with a solitary kidney. Radionuclide studies were carried out using 100 MBq 99Tcm-mercaptoacetyl triglycine (MAG3), 1 h after administration of 50 mg captopril, and repeated in baseline condition when abnormalities were observed in the provocative study. Scintigraphic diagnosis of RAS was based on analysis of captopril-induced changes of the radiorenographs. Overall, 12 patients with a solitary kidney were investigated, and scintigraphic results compared to angiographic findings. All five patients with positive CRS showed an RAS > 50%, whereas only one of the seven patients with negative CRS was affected by RAS. A significant fall in mean arterial pressure was recorded after captopril administration (123 +/- 12 mm Hg before versus 108 +/- 11 after), but no serious side effects were observed. Our results demonstrate that captopril-induced modifications of the renogram could effectively be used to diagnose the presence of RAS. Captopril renal scintigraphy may therefore be suggested as a reliable and safe noninvasive approach to evaluate hypertensive patients with a solitary kidney.

CA-549 serum levels in breast cancer monitoring.

CA-549 serum levels were assessed in 288 patients, 156 with early breast cancer (after surgery) and 132 with advanced breast cancer. CA-549 was abnormal (> 12 U/ml) in 25/156 patients (16%) without clinical signs of disease after surgery (median 9 U/ml), in 49/60 patients (82%) with disease in progression (P) (median 50 U/ml), in 19/27 patients (70%) with stationary disease (NC) (median 14 U/ml), in 25/33 patients (76%) with partial remission (PR) (median 18 U/ml) and in 4/12 patients (33%) with complete remission (CR) (median 9 U/ml). CA-549 serum levels correlated mainly with the extent of disease and secondarily with the prevalent metastatic site, higher values being observed in patients with visceral involvement (median 32.5 U/ml). CA-549 serum levels were also assessed in 51 patients at the start of treatment and at the time of objective evaluation: the results underline the concordance of CA-549 behavior with the clinical outcome in 71% of the cases. We conclude that CA-549 is a useful marker for monitoring breast cancer patients during the advanced stages of the disease.

Cerebral SPECT with 99mTc-HMPAO in extracranial carotid pathology: evaluation of changes in the ischemic area after carotid endarterectomy.

The authors report their experience in studying patients undergoing carotid endarterectomy with simple photon emission computed tomography (SPECT). This technique made it possible to identify areas of preoperative cerebral hypoperfusion in 54.8% of the patients which had a good correlation with neurological symptoms. To distinguish gradual changes in the ischemic lesions, a method of assessing the surface of the hypoperfused areas was adopted. In addition, SPECT made it possible to detect a greater number of hypoperfused areas even in sites other than those revealed by CT. Moreover, there was good correlations between the SPECT data and the grade and site of the carotid lesion and the data provided by some intraoperative monitoring procedures. The Authors therefore propose the use of SPECT in the evaluation of patients with cerebrovascular insufficiency following a carotid disease.

Influence of the thyroid on exocrine pancreatic function.

Exocrine pancreatic function was studied in 15 patients with hypothyroidism and 15 healthy subjects by means of the amino acid consumption test, a new tubeless test based on the measurement of plasma amino acid uptake by the pancreas during pancreatic enzyme synthesis stimulation. Nine of the 15 patients were also studied after they had become euthyroid following thyroxine treatment. Pancreatic function was significantly reduced in patients with hypothyroidism compared with healthy subjects. Treatment with thyroxine restored pancreatic function to normal. In two additional hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was found to be significantly decreased. It was concluded that the thyroid gland plays an essential role in maintaining the functional integrity of the exocrine pancreas in humans.

"Low T3 syndrome" in cirrhosis: effect of beta-blockade.

The so-called "low T3 syndrome" has frequently been reported in patients with cirrhosis. In this study, we aimed to determine whether administration of propranolol to such patients leads to further changes in plasma thyroid hormones, since it can affect their peripheral metabolism. Twenty cirrhotics (11 with ascites) whom we investigated showed no clinical evidence of thyroid dysfunction. The free fractions of plasma T3 and T4 (FT3, FT4) were determined by radioimmunoassay before and after the achievement of an effective beta-blockade by propranolol. The activity of the sympathetic nervous system also was evaluated by measuring plasma norepinephrine concentration. Under basal conditions, cirrhotics showed a reduced FT3 (2.45 +/- 0.11 SEM vs 3.55 +/- 0.16 pg/ml; p less than 0.001) and comparable FT4 (7.62 +/- 0.79 vs 9.2 +/- 0.42 pg/ml) and FT3/FT4 ratio (0.38 +/- 0.04 vs 0.42 +/- 0.013) with respect to healthy controls. When patients with ascites were considered apart, a reduction of FT4 was also found (6.78 +/- 0.74 pg/ml; p less than 0.01). In these patients, many of whom showed an increased plasma norepinephrine concentration, an inverse correlation between log FT3/FT4 and log plasma norepinephrine concentration was found (r = -0.79; p less than 0.01). The effective beta-blockade did not lead to significant changes in either FT3 or FT4 or FT3/FT4, whether the patients were considered as a whole (2.52 +/- 0.19 pg/ml, 9.3 +/- 1.41 pg/ml, and 0.36 +/- 0.04, respectively), or were split into groups according to the presence of ascites. When administered to cirrhotics, propranolol did not worsen thyroid hormone abnormalities, thus appearing to be safe in this respect. This may result from an impaired influence of the sympathoadrenergic system on thyroid hormone metabolism.

Omental autoimplantation of splenic tissue and intravenous pneumococcal challenge. A comparative study in rats.

Splenectomized subjects show a higher incidence of myocardial ischemia and of Overwhelming Post-Splenectomy Infection (OPSI). It is doubtful that implanted splenic tissue guarantees an adequate protection from OPSI. The histological characteristics and the capacity of protection from OPSI of two models of omental autoimplantation of splenic tissue in rats were examined. The implanted splenic tissue offers a significant protection from pneumococcal sepsis, even though there is no relation between implant architecture and survival rate.

CA 15.3 and CEA plasma level monitoring in patients with breast cancer.

CA 15.3 and CEA were determined in the serum of 217 patients with early and advanced breast carcinoma. CA 15.3 was high (greater than 30 U/ml) in 1/6 (17%) patients with stage I-II primary tumor, in 4/77 (5%) patients without clinical signs of disease after mastectomy, in 67/102 (65%) patients with advanced disease in progression, and in 13/32 (41%) patients with advanced disease not in progression and undergoing therapy. The corresponding incidences of pathological CEA values (greater than 2.5 ng/ml) were 33, 8, 55 and 14%. The combination of the two markers brings about a certain improvement in the sensitivity for recognising patients with advanced disease in progression (79/102 = 77%). The presence of high values of CA 15.3 is statistically correlated to the prevalent site of metastases (bone and viscera greater than soft tissues). Monitoring the two markers during antitumor therapy in 36 patients showed good accordance (56%) between CA 15.3 changes and response to therapy. The decrease of the marker in patients who achieved partial remission was statistically significant. In conclusion, CA 15.3 is more sensitive than CEA in recognising patients with advanced disease in progression and gives better accordance with the response to therapy. The simultaneous use of the two markers may be useful in the follow-up of operated patients and in monitoring the disease during treatment.

Spontaneous circadian fluctuations of prostate specific antigen and prostatic acid phosphatase serum activities in patients with prostatic cancer.

Spontaneous circadian variations of prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), determined simultaneously by radioimmunoassay (RIA), were investigated by multiple sampling, over a 24-hour period, in 32 patients with prostatic cancer. In 29/32 patients (91%), the coefficient of variation of 24-hour values, for either marker, was greater than that of the RIA method at the same range of values; stage D patients showed the greatest spontaneous variability. Fluctuations around the mean of 24-hour values ranged from -65% to +85% for PAP, from -72% to +190% for PSA, occurring random and independently for each marker. Variability was about 20% greater for PSA than for PAP. The existence of spontaneous fluctuations should be considered in multiple marker evaluation of prostatic cancer patients.

A phase-II clinical trial of 4'-epi-doxorubicin in advanced solid tumors.

Sixty-six patients with advanced solid tumors were treated with 4'-epi-doxorubicin at a dose of 90 mg/m2 by rapid IV injection every 21 days until the disease had progressed or to a maximum cumulative dose of 540 mg/m2. Myelosuppression, nausea and vomiting, and alopecia were the almost frequent side effects, but their incidence seemed lower than that after a comparable dosage of doxorubicin. After a cumulative dose of 540 mg/m2 a significant decrease of QRS complex deflection on the electrocardiogram was detected, but no case of congestive heart failure was observed. Partial remission and minor remission were achieved, respectively, in nine (15%) and five (9%) out of 59 evaluable patients for a median duration of 6 months. Partial remission occurred in anthracycline-sensitive tumors like breast cancer (4 of 13), lung cancer (1 of 17), head and neck cancer (1 of 8), gastric cancer (2 of 4), and ovarian cancer (1 of 1).

[Long-term outcome in nonmassive pulmonary embolism. Radiologic, scintigraphic and functional correlation]. / Esiti a distanza dell'embolia polmonare non massiva. Correlazioni radiologiche, scintigrafiche e funzionali.

54 cases of acute pulmonary embolism were followed for 3 to 4 years by serial chest radiography (plain film and tomography) to survey the radiographic outcome of complete and incomplete pulmonary infarcts in man. A perfusion lung scan (99Tcm-MAA), arterial blood gas analysis and spirometric data were recorded at similar time intervals to chest films in 30 patients. Our retrospective study showed that the most common long-term residual radiographic findings were linear pulmonary scars and localized pleural thickening. The analysis of the radiographic abnormalities with the lung scan showed a residual perfusion defect in 29% of cases, with complete clearing of the infarct on chest radiography. Long term impairment of pulmonary function, estimated with arterial blood gas analysis and spirometric tests, was never observed.