Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases.

BACKGROUND: This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin- and irinotecan-based systemic chemotherapy regimens. METHODS: Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2). RESULTS: Of 50 eligible patients, 38 (76%) had received > or =4 lines of chemotherapy. Most presented with synchronous disease (72%), >4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (>48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%. CONCLUSION: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC.

Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution.

BACKGROUND: The study evaluates clinical presentation and outcome of differentiated thyroid cancer (DTC) on a large series of patients homogeneously managed. PATIENTS AND METHODS: A cohort of 1503 DTC followed according to a standardized protocol entered the study. Main outcome measures were clinical presentation at the diagnosis, survival, morbidity and prognostic risk factors. RESULTS: Median age at diagnosis was 46 years. Papillary cancer and low pathological tumor-node-metastasis stages represented >80% of cases. Cancer specific survival at 5, 10 and 15 years was 98.6%, 94.7% and 87.4%; 10-year disease-free and progression-free survivals were 96.8% and 17.1%, respectively. Cancer-specific mortality rate was 2.5% [95% confidence interval (CI) 1.7% to 3.4%], recurrence rate was 0.6 % while morbidity rate was 12.6% (95% CI 11% to 14%). Response to radioiodine treatment is the strongest predictor of a good outcome in multivariate analysis (hazard ratio 211, P < 0.0001). Other independent predictor variables are sex, age, histology and distant metastases for survival and metastases for morbidity. CONCLUSIONS: A rigorous initial therapeutic approach leads to a better survival and a very low morbidity. Patients who do not respond to radioiodine treatment have a worse prognosis.

Delivery of selective internal radiation therapy complicated by variant hepatic vascular anatomy.

"Difficult vascular anatomy" is a challenge for Interventional Radiologists especially in liver directed therapies such as trans arterial radio embolization. Trans arterial radio embolization is a long and difficult procedure in which the basic knowledge of hepatic and gastro-enteric vascularization, with its high degree of variations, is very important in order to correctly administer the therapeutic drug selectively. In this report, we present a case of an atypical patient affected by an unresectable hepatocellular carcinoma, candidate for Radio-embolization treatment. His vascular anatomy was very difficult to manage, but the Interventional Radiologist was not only able to go over the "difficult anatomy," but also to take advantage of it.

A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism.

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic 131I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, Teff and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD2). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD50 and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD50, expressed as NTD2, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.

A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy with 90yttrium SIR-spheres in unresectable, colorectal liver metastases refractory to i.v. chemotherapy: preliminary results on toxicity and response rates.

BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.

Randomized prospective clinical trial of high-dose epirubicin and dexrazoxane in patients with advanced breast cancer and soft tissue sarcomas.

PURPOSE: We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity. PATIENTS AND METHODS: Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies. RESULTS: In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004). CONCLUSION: DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.

Corticotropin-releasing hormone inhibition of growth hormone-releasing hormone-induced growth hormone release in man.

Recent studies in the rat have shown that intracerebroventricular administration of CRH inhibited spontaneous pulsatile GH secretion and prevented GH-releasing hormone (GHRH)-induced GH release. We have studied the effect of CRH on GHRH-induced GH release in man. In the first study, CRH was injected iv at three different doses (100, 50, or 25 micrograms) at 0800 h together with 50 micrograms GHRH in six men and six women. In a second study, 100 micrograms CRH were given iv at 0800 h, 1 h before the administration of 50 micrograms GHRH in five men and five women. Each subject demonstrated a normal GH response after the administration of 50 micrograms GHRH plus saline. All doses of CRH administered simultaneously with GHRH significantly inhibited GHRH-induced GH release in women [peak value +/- SE after GHRH plus saline, 28.9 +/- 2.9 micrograms/L; after GHRH plus 100 micrograms CRH, 9.9 +/- 0.7 micrograms/L (P less than 0.001); after GHRH plus 50 micrograms CRH, 8.7 +/- 0.8 micrograms/L (P less than 0.001); after GHRH plus 25 microgram CRH, 9.5 +/- 1.6 microgram/L (P less than 0.001]). In contrast, in men, while a dose of 100 micrograms CRH was capable of suppressing GHRH-induced GH secretion (peak value +/- SE, 8.1 +/- 0.6 vs. 20 +/- 2.9 micrograms/L; P less than 0.001), no inhibition was observed after 50- and 25-micrograms doses. When 100 micrograms CRH were injected 1 h before the administration of 50 micrograms GHRH, it strongly inhibited GHRH-induced GH secretion in both men (peak value +/- SE, 6.2 +/- 2.8 vs. 24.6 +/- 5.9 micrograms/L; P less than 0.02) and women (peak value +/- SE, 14.2 +/- 4.5 vs. 37.8 +/- 6.7 micrograms/L; P less than 0.005), and this inhibition lasted up to 2 h post-CRH administration. These results demonstrate that CRH is capable of inhibiting GHRH-induced GH release in both men and women. Furthermore, the findings suggest that a sexual dimorphism in the neuroregulation of GH secretion may be present in man. In view of the inhibitory action of CRH on GH secretion, simultaneous administration of CRH and GHRH for testing should be avoided in clinical practice.

Corticotropin-releasing hormone inhibition of gonadotropin release and the effect of opioid blockade.

We studied the inhibitory effect of exogenous CRH on pulsatile gonadotropin secretion and the role of endogenous opioid peptides in this phenomenon in normal women. To do so, we infused human CRH (100 micrograms/h for 3 h) into 15 normal women during the midluteal phase of their menstrual cycle and studied its effect on both basal (10 women) and GnRH-stimulated (5 women) plasma gonadotropin levels. CRH infusion induced a significant decrease in plasma LH and FSH levels in all women. The decline in plasma LH (62%) was greater than that in FSH (36%). Plasma LH and FSH concentrations returned to basal levels within 30 min after the end of the CRH infusion. CRH infusion did not alter the gonadotropin response to GnRH. We also infused naloxone plus CRH in the 10 women who had received CRH alone during the midluteal phase of a different cycle. Addition of naloxone to CRH (5 women) reversed the LH and FSH inhibition when naloxone was started 1 h after the start of the CRH infusion. When naloxone was started 1 h before CRH infusion (5 women), plasma LH and FSH concentrations did not change. Plasma cortisol increased similarly during both the CRH and CRH plus naloxone infusions; the mean cortisol levels at the end of the CRH and CRH plus naloxone infusions were 497 +/- 40 (+/- SE) and 484 +/- 41 nmol/L, respectively, compared to 240 +/- 14 nmol/L after saline infusion (P less than 0.001). These results demonstrate that in normal women during the midluteal phase of the menstrual cycle, CRH inhibits the secretion of both LH and FSH. The CRH-induced inhibition of gonadotropin secretion is primarily mediated by endogenous opioid peptides, and this effect is not dependent on glucocorticoid levels. We suggest that the disruptive effect of stress on reproductive function in the women could be, at least in part, dependent on decreased gonadotropin secretion induced by elevated endogenous CRH levels.

Sexual dimorphism of pyridostigmine potentiation of growth hormone (GH)-releasing hormone-induced GH release in humans.

Sex differences in the neuroregulation of GH secretion are not now known in humans. To investigate whether activation of cholinergic tone by pyridostigmine could cause a sex-related difference in the pituitary responsiveness to GH-releasing hormone (GHRH), we have studied the GH response to GHRH in 16 normal subjects (8 men and 8 women) tested after oral placebo or different doses of pyridostigmine (30, 60, and 120 mg). Each subject presented a normal response after iv administration of 50 micrograms GHRH and placebo. In men each dose of pyridostigmine induced a significant increase in the GH response to GHRH, as assessed by both the maximal GH peak and the area under GH curve. In women, on the contrary, the GH response to GHRH was not potentiated by pretreatment with pyridostigmine at any given dose. Only five female subjects were tested with 120 mg pyridostigmine because of the severe side-effects of the drug at this dosage. Our present data strongly suggest that in humans there is a sex-related difference in the neuroregulation of GH secretion and this is probably expressed through a different cholinergic tone.

Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases.

UNLABELLED: This study evaluates the short- and long-term therapeutic efficacy of 186Re-1,1-hydroxyethylidene diphosphonate (HEDP) in the palliation of painful bone metastases and the influence of variables before therapy in determining the characteristics of pain palliation. METHODS: Sixty patients with painful bone metastases from different tumor types were treated with 1406 MBq 186Re-HEDP. After treatment, the patients were followed up clinically at weekly intervals for the first month and monthly thereafter up to 1 y, until death or pain relapse. Pain response was graded as complete, partial, minimal, or absent using the Wisconsin test scoring system. Duration of pain relief, performance status, tumor markers, serum alkaline phosphatase levels, hematologic toxicity, and metastatic bone progression were also evaluated. RESULTS: Overall, 80% of individuals experienced prompt relief of pain, with 31% complete, 34% partial, and 15% minimal responses. Transient World Health Organization grade 1-2 hematologic toxicity was apparent, with a decrease in the mean platelet (32%) and mean leukocyte (18%) counts at 3 and 4 wk, respectively. The degree of pain response did not correlate with any pretreatment variable. The duration of pain relief ranged from 3 wk to 12 mo and correlated positively with the degree of response (P = 0.02) and negatively with pretreatment scintigraphic scores and alkaline phosphatase levels (P = 0.02). CONCLUSION: 186Re-HEDP is effective for fast palliation of painful bone metastases from various tumors. The effect tends to last longer if patients are treated early in the course of their disease.

Technetium-99m-MIBI scintigraphy in the assessment of neoadjuvant chemotherapy in breast carcinoma.

UNLABELLED: Presurgical neoadjuvant chemotherapy (PSNC) is the treatment of choice for patients with locally advanced breast carcinoma (LABC). Accurate assessment of tumor response is important in planning subsequent treatments. Conventional response assessment by mammography and clinical evaluation is not fully reliable. This study evaluates the diagnostic yield of serial 99mTc-MIBI scintigraphy in the assessment of LABC response to PSNC. METHODS: Twenty-nine patients affected by LABC underwent clinical, mammographic and 99mTc-MIBI scintigraphy before and after 3 cycles of FEC (500 mg/m2 5-fluorouracil, 50 mg/m2 epirubicin and 400 mg/m2 cyclophosphamide) on Days 1 and 8. Surgery was planned for 15 days after the third cycle of chemotherapy. Pathological status was obtained after surgery in all patients. RESULTS: Sensitivities (i.e., true-positive ratios) for a correct prediction of tumor presence after PSNC were 65% for scintigraphy, 35% for clinical evaluation and 69% for mammography. Specificities (i.e., true-negative ratios) for a correct prediction of tumor absence after PSNC were 100% for scintigraphy, 67% for clinical evaluation and 33% for mammography. Technetium-99m-MIBI uptake in this series did not correlate with P-170 expression, proliferating cell nuclear antigen, Her-2/neu oncogene protein, antihuman endothelial cell CD31 antigen and estrogenic and progestinic receptor status. CONCLUSION: Technetium-99m-MIBI scintigraphy is effective in monitoring the response to PSNC in LABC patients. Its diagnostic yield is clearly superior to clinical evaluation alone. Scintigraphy performs as does mammography in patients with negative response, but it is clearly superior in patients with positive response.

99mTc-MIBI scintimammography using a dedicated nuclear mammograph.

UNLABELLED: This study reports on a prototype single-photon emission mammograph (SPEM) dedicated to 99mTc-hexakis-2-methoxyisobutile isonitrile (MIBI) scintimammography. Main technical features are reported together with physical performance. Preliminary patient data are also reported. METHODS: The SPEM detector head is composed of a CsI(T1) scintillating array coupled to a Hamamatsu R3292 position-sensitive photomultiplier tube with crossed-wire anode. The high-resolution collimator is 35-mm thick with a 1.7-mm hole diameter and a 0.2-mm septal thickness. The electronic acquisition system is composed of five integrated cards with computation based on high-speed programmable microprocessors. The readout electronics include correction maps for on-line energy correction and spatial uniformity. The small size of the detector head allows the use of mechanical breast compression to minimize detection distance and tissue scatter. After physical SPEM performance evaluation in vivo scintimammography was performed in 29 patients and was compared with a state-of-the-art Anger camera. RESULTS: The SPEM showed an intrinsic spatial resolution of 2 mm, an energy resolution of 23% FWHM at 122 keV and spatial uniformities of 18% (integral) and 13.5% (differential). The SPEM imaged one 0.4-cm carcinoma missed by the Anger camera and resolved as separate lumps an irregular focal uptake on the Anger camera image. The remaining cases yielded concordant results. CONCLUSION: The SPEM prototype presented in this study shows adequate physical characteristics for 99mTc-MIBI scintimammography.

Corticotropin-releasing hormone inhibition of paradoxical growth hormone response to thyrotropin-releasing hormone in insulin-dependent diabetics.

A paradoxical growth hormone (GH) response to thyrotropin-releasing hormone (TRH) has been observed in type 1 diabetic patients and was hypothetically attributed to a reduced hypothalamic somatostatin tone. We have previously reported that corticotropin-releasing hormone (CRH) inhibits GH response to growth hormone-releasing hormone (GHRH) in normal subjects, possibly by an increased release of somatostatin. To study the effect of CRH on anomalous GH response to TRH, we tested with TRH (200 micrograms intravenously [IV]) and CRH (100 micrograms IV) + TRH (200 micrograms IV) 13 patients (six males and seven women) affected by insulin-dependent diabetes mellitus. A paradoxical GH response to TRH was observed in seven of 13 patients, one man and six women. In these subjects, the simultaneous administration of CRH and TRH significantly reduced the GH response to TRH, as assessed by both the maximal GH mean peak +/- SE (2.18 +/- 0.67 v 9.2 +/- 1.26 micrograms/L, P less than 0.005) and the area under the curve (AUC) +/- SE (187 +/- 32 v 567 +/- 35 micrograms.min/L, P less than .001). CRH had no effect on TRH-induced thyroid-stimulating hormone (TSH) release. Our data demonstrate that the paradoxical GH response to TRH in patients with type 1 diabetes mellitus is blocked by CRH administration. This CRH action may be due to an enhanced somatostatin release. Our data also show that exogenous CRH has no effect on TSH response to TRH, thus suggesting the existence of separate pathways in the neuroregulation of GH and TSH secretion.

Cardiotoxicity of high-dose-rate epirubicin evaluated by angiocardioscintigraphy.

Cardiotoxicity of high dose rate epirubicin (140-160 mg/m(2) as a bolus every 21 days up to a cumulative dose of 1280 mg/m(2)) was evaluated by angiocardioscintigraphy in 121 patients with advanced neoplastic disease and no preexisting cardiac risk factors. LVEF was measured in each patient before chemotherapy and during the treatment at different epirubicin cumulative dosages. The cases were subdivided into 3 groups: Group A=121 basal studies; Group B=93 studies performed under 800 mg/m(2); Group C=44 studies performed over 800 mg/m(2). A statistically significant decrease of LVEF was observed only at cumulative doses over 800 mg/m(2) (mean LVEF: 53% +/- 11% in Group C vs 64% +/- 7% in Group A). In no case was chemotherapy stopped prematurely and no case of heart failure was observed. A decrease of LVEF 10 units was recorded in 15 patients and 12 of them had been treated with over 800 mg/m(2). No clinical signs of severe cardiac failure were observed in these patients during a follow-up of 5-17 months. In conclusion, epirubicin treatment at high dose rate up to a cumulative dose of 1000 mg/m(2) does not increase the risk of clinically relevant cardiomyopathy and an LVEF decrease of 10 units should not in itself lead to chemotherapy termination in responsive patients.

Primary hyperparathyroidism. Our experience.

We report our experience in the clinical presentation and management of 12 patients with primary hyperparathyroidism, who underwent successful surgery. Comparing our results with those previously reported in the literature, we have attempted to correlate the kind of parathyroid lesion, the magnitude of hypercalcemia and PTH increase, and clinical symptoms. Often these relationships are intriguing; we have tried to classify our patients describing four groups, according to clinical and humoral findings: 1) patients with very mild hypercalcemia and aspecific symptoms; 2) patients with a finding of recurrent hypercalcemia and prevalent renal involvement; 3) patients with severe hypercalcemia, plurisystemic involvement and general decay; 4) patients with medical emergencies. Finally, some considerations on rare histological pictures (hyperfunctioning carcinoma, oxyphil cell adenoma) are reported.

[Coexistence of hyperthyroidism and thyroid carcinoma. Description of a clinical case]. / Coesistenza di ipertiroidismo-carcinoma tiroideo. Segnalazione di un caso clinico.

The association of hyperthyroidism and thyroid carcinoma, especially multicentric forms, is an unusual event. We present the case of a 49-year-old woman with clinical and radiological findings of hyperfunctioning thyroid nodule that showed, after a subtotal thyroidectomy, histologic evidence of multicentric carcinoma in one lobe and adenoma in the other lobe. The interest of this clinical case is in the coexistence of an independent adenoma with a multicentric carcinoma, revealed by radical surgery that was necessary for the occurrence of a multinodular goiter. The incidence of this situation could be underestimated in consequence of the current surgical approach to the single "hot" nodule and suggests we pay attention to these patients for the possible presence of malignancy in functionally-inhibited thyroid tissue.

Somatostatin receptors in meningiomas: a scintigraphic study using 111In-DTPA-D-Phe-1-octreotide.

111In-octreotide (Octreoscan) planar scintigraphy was performed in 12 patients with suspected meningioma. The scan was positive in 10 patients with meningioma and negative in two patients with acoustic neurinoma assisting in the differential diagnosis. Good quality images were obtained as early as 2 h after injection and there was no increase in diagnostic quality at 24 h. No adverse effects were observed to radiopharmaceutical administration. The following conclusions are drawn: 111In-octreotide is a safe and fast test which can increase the specificity of traditional neuroimaging procedures.

Radiosensitization with low-dose carboplatin enhances pain palliation in radioisotope therapy with strontium-89.

Strontium-89 (89Sr) is currently used for the treatment of painful bone metastases. This study reports the use of low-dose carboplatin as a radiosensitizer in 89Sr radioisotope therapy. The study design comprised two groups: 15 patients treated with 89Sr (148 MBq) followed by carboplatin (100 mg m-2 at 7 and 21 days) and 15 patients treated with 89Sr alone. Their pain response was assessed 8 weeks post-injection. Follow-up was continued for up to 1 year in the survivors. Twenty-seven patients were evaluable. A pain response was observed in 20 of 27 (74%) patients. The pain response in the patients treated with 89Sr and carboplatin was clearly superior to that seen in the patients treated with 89Sr alone (P = 0.025), whereas survival was only marginally better in the combined treatment group (8.1 vs 5.7 months, P = 0.19). No clinically significant adverse effects or myelosuppression by carboplatin were observed. Low-dose carboplatin enhances the effects of 89Sr radioisotope therapy on pain from bone metastases.

Myocardial 123I-MIBG kinetics in acutely hypothyroid patients with differentiated thyroid carcinoma.

Marked changes in cardiac function have been noted in patients with hyperthyroidism or hypothyroidism due both to changes in sympathetic system function and to biochemical modifications of myocardial tissue. Metaiodobenzylguanidine (MIBG), an analogue of norepinephrine, can be used to evaluate myocardial sympathetic tone. Here, we report myocardial 123I-MIBG kinetics in patients with differentiated thyroid carcinoma undergoing acute hypothyroidism followed by hormonal replacement as part of their routine clinical follow-up. Ten patients with differentiated thyroid carcinoma in acute hypothyroidism (A) and on hormonal replacement with thyroxine (150 micrograms.day-1) and triiodothyronine (20 micrograms.day-1) (B) underwent scintigraphic imaging 20 min and 4 h after injection of 111 MBq of ultra-high specific activity 123I-MIBG. No patient had cardiac disease or was taking medications that could interfere with cardiac or autonomic system function. Cardiac MIBG kinetics (heart-to-mediastinum, H/M, ratio and myocardial washout rate), serum norepinephrine, T3, T4, FT3, FT4, TSH, CPK, CPK-MB, blood pressure and ECG were evaluated. Systolic and diastolic blood pressure did not differ significantly between state A and state B. In the acute hypothyroid state (A), the prevalence of non-specific ST-T abnormalities was 70% and heart rate was significantly different (P < 0.001) than in state B. Norepinephrine and CPK-MB levels were higher during hypothyroidism, but this did not reach statistical significance. A positive correlation between early H/M and delayed H/M in the hypothyroid state (r = 0.57) and an even higher positive correlation between early H/M and delayed H/M in the euthyroid state (r = 0.91) were seen. The myocardial and mediastinal MIBG washout rates were significantly different between the hypothyroid and euthyroid states (P < 0.05), whereas the lung washout rate did not differ significantly between the two metabolic states. We conclude that the myocardial washout rate during hypothyroidism is clearly increased (P < 0.005) with a subclinical derangement of myocardial adrenergic innervation, which is rapidly reversed with hormonal therapy.

Somatostatin receptor imaging in small cell lung cancer using 111In-DTPA-octreotide: a preliminary study.

Small cell lung cancer is a common and aggressive disease. Combined multiagent chemotherapy and radiotherapy can improve short-term prognosis, but long-term prognosis remains dim. Somatostatin receptors have been identified on the cellular surface of subsets of this cancer and may be associated with less aggressive evolution. Moreover, medical therapy with somatostatin analogues holds promise for neoplastic growth control. Planar scintigraphy has been performed in 15 patients with histologically proven small cell lung cancer at 4 and 24 h after the intravenous (i.v.) injection of 185 MBq 111In-octreotide (Octreoscan, BYK-Gulden). No short-term adverse effects were recorded; tumour uptake of the radiopharmaceutical was observed in 13 patients at 4 h and in 12 patients at 24 h suggesting more extensive disease than apparent by computed tomography (CT). It is highly likely that the 24 h uptake reflects the presence of somatostatin receptors on the tumour. Previous chemotherapy does not seem to play a key role in tumour visualization. 111In-octreotide is a suitable radiopharmaceutical for in vivo evaluation of somatostatin receptor status of small cell lung cancer. Quantitative scintigraphic methods are needed to investigate nonspecific binding and receptor kinetics.