Effect of chemotherapy on somatostatin receptor detection with octreotide scintigraphy in hormone-refractory prostate cancer patients.

BACKGROUND: Neuroendocrine cells have been found in all stages of prostate cancer. Neuroendocrine differentiation of prostate adenocarcinoma is a possible target for therapeutic strategies, such as administration of GH analogs (e.g., somatostatin), especially in patients with hormone-refractory prostate cancer (HRPC). The presence of receptors for these drugs in tumor cells and tissues is essential and is assessed with 111In-octreotide scintigraphy (Octreoscan). The relationship between these receptors and chemotherapy, the new standard therapy for HRPC, is unknown. PATIENTS AND METHODS: 111In-octreotide scintigraphy was performed on 20 patients affected by HRPC, all with metastatic disease. Chemotherapy with a single agent was also administered to all patients. RESULTS: In 63% of the patients, all metastases were negative to Octreoscan. Several metastases were positive in 37% of patients only, compared to 94% previously described in a chemotherapy-naive population. CONCLUSION: Chemotherapy seemed to reduce the cellular receptors for somatostatin analogs.

Long-term follow-up of two children with a variant of mild autosomal recessive osteopetrosis undergoing bone marrow transplantation.

Malignant autosomal recessive (AR) osteopetrosis represents an absolute indication for bone marrow transplantation (BMT). Over the last 15 years, almost 100 BMTs for osteopetrosis have been reported. The median age at transplant of most patients is 4 months. Very few cases of mild AR osteopetrosis have been described. Here, we report the good outcome of two cases of mild AR osteopetrosis with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling transplant undergone at 5 and 12 years of age, respectively. At the time of BMT, severe visual impairment was present in both children. Bone biopsy demonstrated hypermineralization with virtual obliteration of the medullary spaces, rare microfoci of hematopoiesis and marked deficiency in osteoclastic activity. Successful engraftment was complicated by hypercalcemia, controlled by a combination of bisphosphonate, phosphate infusions, vigorous hydration and calcitonin. Following BMT, radiological and histological findings showed extensive bone resorption with marked augmentation of the osteoclasts in normalized marrow. No improvement was observed in visual acuity, despite complete remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only chance of curing mild AR osteopetrosis.

131I-metaiodobenzylguanidine (131I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients.

Incomplete response to therapy may compromise the outcome of children with advanced neuroblastoma. In an attempt to improve tumour response we incorporated 131I-metaiodobenzylguanidine (131I-MIBG) in the treatment regimens of selected stage 3 and stage 4 patients. Between 1986 and 1997, 43 neuroblastoma patients older than 1 year at diagnosis, 13 with stage 3 (group A) and 30 with stage 4 disease (group B) who had completed the first-line protocol without achieving complete response entered in this study. 131I-MIBG dose/course ranged from 2.5 to 5.5 Gbq (median, 3.7). The number of courses ranged from 1 to 5 (median 3) depending on the tumour response and toxicity. The most common acute side-effect was thrombocytopenia. Later side-effects included severe interstitial pneumonia in one patient, acute myeloid leukaemia in two, reduced thyroid reserve in 21. Complete response was documented in one stage 4 patient, partial response in 12 (two stage 3, 10 stage 4), mixed or no response in 25 (ten stage 3, 15 stage 4) and disease progression in five (one stage 3, four stage 4) Twenty-four patients (12/13 stage 3, 12/30 stage 4) are alive at 22-153 months (median, 59) from diagnosis. 131I-MIBG therapy may increase the cure rate of stage 3 and improve the response of stage 4 neuroblastoma patients with residual disease after first-line therapy. A larger number of patients should be treated to confirm these results but logistic problems hamper prospective and coordinated studies. Long-term toxicity can be severe.

A Cys634Gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis.

Germ-line mutations of the RET proto-oncogene, involving five cysteine residues at codons 609, 611, 618, 620 and 634, are associated with two variants of the inherited cancer syndrome multiple endocrine neoplasia type 2: type 2A and familial medullary thyroid carcinoma. The association of multiple endocrine neoplasia type 2A with the dermatological disorder cutaneous lichen amyloidosis has already been reported, and mutations in the Cys634 have been identified in different families. We describe here an additional pedigree in which multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis cosegregate. A Cys634Gly was identified by direct sequencing of the RET proto-oncogene exon 11 in the affected individuals. The mutation creates a new HaeIII site, and restriction analysis performed on all family members rules out the presence of the altered allele in two children and consequently the risk of developing thyroid tumors. These results emphasize the role of molecular analysis of the RET proto-oncogene in diagnosing presymptomatically those individuals at risk of inheriting the disease allele.

Radioiodinated meta-iodobenzylguanidine in the diagnosis of childhood neuroblastoma.

In a group of 97 patients aged from 6 months to 12 years, all with suspected or proven neural crest tumours, metaiodobenzylguanidine (MIBG) scintigraphy was performed at the time of diagnosis and, in some instances, after induction chemotherapy. All the patients underwent a tumour biopsy with cytological and histological analysis, in addition to imaging examinations such as X-rays, ultrasound, computed tomography and magnetic resonance, within a short period before or after scintigraphy. In 82 of 97 cases MIBG was effective in detecting the primary tumour, hence the technique's sensitivity was 84%. A significant different of sensitivity between [131I]MIBG and [123I]MIBG was not demonstrated. As regards metastatic locations, MIBG scans revealed one or more bone metastases in 12 cases, bone marrow involvement (assumed to be present when diffuse and symmetric uptake in the spine, pelvis and possibly other skeletal sites were visualized) in 9 cases, and focal liver metastases or hepatomegaly in 4 cases. Probably owing to the restrictive diagnostic criterion adopted or to the early phase of the bone marrow involvement, the last was found by biopsy but missed by MIBG in 25 cases. The overall sensitivity in detecting metastases was low (48%), but it was much higher if only bone metastases were considered (81%). Twenty-nine patients who had positive scans at diagnosis were checked following 1-2 courses of induction chemotherapy (IC). MIBG scans remained positive in 22 primary tumours, while 7 primary masses were no longer detected. Out of 12 cases showing metastases at diagnosis, two cases with liver lesions became normal and in one case some, but not all, of the bone lesions were not detectable; 4 cases remained abnormal, while in 5 cases bone marrow involvement was not confirmed. Three cases were confirmed to be true negatives; in 4 other cases bone marrow involved not showing at diagnosis was revealed and confirmed by biopsy; 3 cases in which bone marrow involvement was not revealed by MIBG at diagnosis, had normal MIBG and biopsy results after IC; finally, 2 false negative bone marrow cases and 5 true negative cases at diagnosis remained unchanged, but were not checked by biopsy. Performing total body MIBG scintigraphy in childhood neuroblastoma at diagnosis is useful: 1) to predict the nature of the masses detected by other imaging techniques, when biopsy has not yet been performed; 2) for more accurate tumour staging, in addition to standard imaging investigations, MDP scintigraphy and bone marrow aspiration biopsy, thanks to its ability to detect metastatic lesions; 3) to anticipate the decrease in sensitivity of the technique in detecting both the primary mass and the metastases following induction chemotherapy.

Place of meta-[131I]iodobenzylguanidine in the treatment of neuroblastoma: the Genoa experience.

The aim of this paper is to focus on our previous experience with the treatment of Group 3 and 4 neuroblastoma patients and on the therapeutic use of [131I]MIBG, to better define the role of this radioactive drug in the treatment of neuroblastoma (NB). Analysis of the studies on Group 3 patients treated with chemotherapy and surgery showed that the progression-free survival (PFS) increased from 45% for patients treated before 1985 to 63% for patients treated in the period of 1985-1989 and to 78% for patients treated after 1989. [131I]MIBG administered in 17 Group 3 patients who did not achieve a radical excision of the primary resulted in 7 partial response (PR) and 5 minor response (MR), with 10 cases of long term survival. Results in Group 4 patients confirmed the good prognosis in the subset of children aged 6-12 months at diagnosis (PFS 86% at 5 years). In patients aged > 12 months at diagnosis intensive induction chemotherapy induced a higher response rate of 69% and PFS was 26% at 5 years. [131I]MIBG administered in advanced stage 4 patients induced a response in 50% of the cases (2 complete response [CR], 13 PR and 2 MR out of 34 children) and 8 children treated for residual primary (4 cases) or residual bone metastases (4 cases) are long term survivors. We conclude that [131I]MIBG is the treatment of choice in Group 3 patient with a residual primary tumor and could contribute to consolidate the response obtained in Group 4 patients.

Primary hypothyroidism as a consequence of 131-I-metaiodobenzylguanidine treatment for children with neuroblastoma.

BACKGROUND: 131-I-metaiodobenzylguanidine is a radioiodinated compound selectively concentrated by cells of neuroectodermal origin, including neuroblastoma cells, for this reason it may represent a promising treatment modality for neuroblastoma in childhood. Although a potential side effect of 131-I-MIBG administration is thyroid dysfunction, relatively few data are reported about this issue. METHODS: A series of 14 long term surviving patients with neuroblastoma who had been treated with 131-I-MIBG courses ranging from 2.5 to 5.5 gigabecquerels after surgical and conventional pharmacologic therapy is reported. RESULTS: Twelve patients developed primary hypothyroidism that was clinically overt in 8 patients and compensated in 4 patients within 6-12 months of completion of 131-I-MIBG administration. Only in two patients was thyroid function spared. Significant correlations between the cumulative dose of 131-I-MIBG and the degree of thyroid failure were not found. CONCLUSIONS: Primary hypothyroidism appears to be a common side effect in children with neuroblastoma treated with 131-I-MIBG. This finding suggests that methods to preserve thyroid function other than oral administration of iodide should be sought.

Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol.

The aim of this study was to assess the effect of a long-term course of high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone disease (HBD) and functional mass of parathyroid glands of chronically hemodialyzed uremic (CHU) patients. We prospectively studied nine CHU patients treated with CLT, 30 ng/kg/body wt, i.v., thrice weekly over a period of eight months. Plasma concentrations of intact parathyroid hormone (iPTH), bone GLA protein (bGLA) and bone isoenzyme of alkaline phosphatase (biALP) were sampled throughout. Transiliac bone biopsies were made before and after the start of CLT therapy. Double scanning scintigraphy of the neck with 201Tl-99Tc was made before, during and eight months after the start of the treatment. All patients but one, who later responded to higher than planned CLT doses, had significant decreases of plasma iPTH (F = 76; P < 0.0001; ANOVA). The mean pretreatment value of PTH was 966 +/- 160 (mean +/- SE) pg/ml and it had decreased significantly by the first week (T = 2.4, P < 0.04), and had fallen an average of 80% by the 35th week. Ionized plasma calcium concentration was 1.19 +/- .01 mmol/liter which rose significantly (F = 13.5; P < 0.0001) by the 14th week to maximal peak levels, averaging 1.34 +/- .02 mmol/liter. Changes in biALP were parallel to those of iPTH, while bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Semiquantitative evaluation of regional cerebral flow by means of SPECT with 99mTc-hexamethyl-propylene amine oxime in hypertensive patients under treatment.

Cerebral SPECT with 99mTc-HM-PAO allows a semiquantitative evaluation of regional cerebral blood flow (rCBF). Using this method we studied 25 patients affected by slight-to-moderate degree hypertension, in effective pharmacological treatment, and a control group of normotensives. On the cross-sections symmetrical ROIs were traced at the level of the cerebral lobes and the cerebellum. From the counts obtained on the ROIs the rCBF values were calculated in percentage units with Lassen's algorithm. We found no significant differences between the rCBF values of the two groups. In 5 hypertensive patients, however, focal areas of hypoperfusion were evidenced. These patients did not differ from the other hypertensives by pressure levels or other risk factors. Neurological, tomographic and flowmeter examinations of the supraaortic arteries proved to be normal. It is possible that SPECT with 99mTc-HM-PAO identifies a subgroup of hypertensives at risk of future cerebrovascular pathology despite the setting up of an effective antihypertensive therapy.

Predicting cardiac mortality after uncomplicated myocardial infarction by exercise radionuclide ventriculography and exercise-induced ST segment elevation.

In 183 consecutive patients with recent, uncomplicated myocardial infarction, the following variables were associated with 4-year cardiac death: haemodynamic decompensation with exercise (P = 0.01), left ventricular ejection fraction at rest (P = 0.004) and at peak exercise (P = 0.003), persistent ST segment elevation at rest in the area of infarction = (P = 0.004), exercise-induced ST segment elevation (P = 0.02), and late aneurysmal evolution (P = 0.01). Exercise left ventricular ejection fraction was the sole variable selected by Cox regression analysis as an independent predictor of cardiac death. In 40 patients with ST segment elevation at rest, left ventricular ejection fraction was 42 +/- 17% at rest and 40 +/- 18% at peak exercise, versus 52 +/- 12% and 52 +/- 14% in the remaining patients (both P less than 0.01). Among these 40, 16 (all with anterior infarction) also had exercise-induced ST segment elevation; their ejection fraction was 32 +/- 13% at rest, 30 +/- 13% during exercise, versus 53 +/- 15% and 53 +/- 15% in 129 patients with no ST segment elevation either at rest, or during exercise (both P less than 0.01). The 4-year risk of death was 20% in the former 40 patients, 36% in the latter 16, while in the complete absence of ST segment elevation, such risk was 3%. All 14 patients with ST segment elevation only during exercise were alive after 4 years: their left ventricular ejection fraction was 47 +/- 12% at rest, 45 +/- 13% with exercise. ST segment elevation was associated with late aneurysmal evolution but not with exercise-induced ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

[131I]metaiodobenzylguanidine therapy in advanced neuroblastoma.

Forty-two children with advanced neuroblastoma who either failed with first-line therapy or relapsed after achieving a complete remission, were considered for treatment with [131I]metaiodobenzylguanidine (131I-MIBG). We subdivided 42 cases into 5 groups, in accordance with the stage of disease at diagnosis, response to first-line therapy and relapse. A total of 99 courses of 131I-MIBG were administered with doses ranging from 2.8 to 6.0 GBq. One child received six courses, 3 four courses, 18 three courses, 6 two courses and 15 one course of 131I-MIBG. The total delivered dose in single measurable lesions ranged from 286 to 1691 cGy with an uptake factor ranging from 3% to 10%. We obtained a major response in primary tumors, and a long-term response was observed in 5 cases, lasting more than 2 years without further chemotherapy.

Treatment of advanced neuroblastoma with I-131 meta-iodobenzylguanidine.

From February 1986 to December 1988, 31 children with advanced pretreated neuroblastoma were treated with 131-I meta-Iodobenzylguanidine (131-MIBG). Thirteen children had been resistant to first-line therapy, three had suffered a local relapse, and fourteen had suffered a disseminated relapse without over bone marrow infiltration. One child was treated initially because of resistance to first-line therapy, and subsequently for a local relapse. A total of 72 courses of 131-MIBG was administered, with doses ranging from 2.8 to 6.0 GBq (median, 3.7 GBq). One child received five courses, two four courses, 13 three courses, four two courses, and 12 one course of 131-MIBG. The most common toxic effect was thrombocytopenia, with a platelet level of less than 50,000/cmm occurring after 19 of 60 evaluable courses. A leukocyte count less than 1000/cmm was seen only once. There were six major responses (two complete) lasting 4 to 9 months, and two minor responses lasting longer than 38 and 44 months. Responses were seen more commonly in children whose only lesion was a residual primary tumor and in children who had not been pretreated who experienced disseminated relapse. Further studies of the role of 131-I meta-Iodobenzylguanidine in treatment of neuroblastoma are needed.

Scinticisternography in presenile and senile degenerative disease.

86 patients suffering from various senile and presenile degenerative diseases were studied using scinticisternography with In111-DTPA. Flow reversal and delayed clearance were observed in 62 of these patients. These alterations, possibly related to the cerebrospinal fluid dynamics, show the aspecificity of the SC picture. The SC picture does not seem to be correlated to the clinical signs.

Left ventricular thrombi: changes in size and in platelet deposition during treatment with indobufen and ticlopidine.

This study was designed to evaluate whether indobufen and ticlopidine can induce changes in the size of left ventricular thrombi and variations in the deposition of platelets on thrombus surface. Forty-seven patients with left ventricular thrombosis, who were not treated with antithrombotic drugs, were prospectively evaluated with 111In-oxine platelet imaging and two-dimensional echocardiography. The first scintigraphic examination was negative in 15 of the 47 patients with left ventricular thrombosis, thus they were excluded from further evaluation. The remaining 32 patients with evidence of labeled platelet deposition on the thrombus were divided into three groups. Group 1 comprises 11 patients treated with different doses of ticlopidine: 6 with 250 mg/day, and 5 with 500 mg/day. Group 2 comprises 12 patients who received 400 mg/day of indobufen. Group 3 comprises 9 patients who were not treated with antithrombotic drugs. All 32 patients underwent repeated 111In-oxine platelet imaging and echocardiography 40 +/- 11 days after the first examination. During treatment with ticlopidine, deposition of labeled platelets on the thrombus became absent in 2 patients (500 mg/day), and reduced in 5 (2 treated with 250 and 3 with 500 mg/day). A decrease of platelet deposition on the thrombus was also observed in 5 of the 12 patients receiving indobufen and in only 1 of 9 controls. With regard to thrombus dimensions, 1 patient treated with ticlopidine showed a decrease in thrombus size associated with a reduction of the scintigraphic activity. In conclusion, a decrease of the platelet uptake on the thrombus surface, without significant changes in the size, was detected in most patients during treatment with indobufen and ticlopidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in vascularity of liver tumours after hepatic arterial embolization with degradable starch microspheres.

The role of vascularity as a prognostic factor was investigated in 35 patients undergoing arterial chemotherapy for liver tumours. Compared with parenchyma, tumour vascularity was classified as hot (18 cases), cold (12 cases), and mixed (12 cases) using 99mTc-macroaggregated albumin (MAA) hepatic arterial scans. The proportion of patients showing complete and partial responses to treatment was higher in the hot group (56 per cent) than in the combined cold and mixed group (12 per cent). In 15 cases (six hot, six cold and three mixed lesions), additional MAA scans were performed immediately after arterial embolization with degradable starch microspheres (DSMs). Either complete or partial reversal of tumour vascularity was observed after DSM-embolization in five and seven cases respectively, two and two of them respectively showing native cold lesions. As tumour vascularity appears to be a prominent prognostic factor, DSM-embolization should improve the efficacy of treatment by improving liver extraction of drugs and causing flow redistribution towards hypovascular areas.

[The role of endorectal echography for determining the extent of an operation]. / Rol' éndorektal'noi ékhografii dlia opredeleniia ob''ema operatsii.

The paper discusses the usefulness of endorectal echotomography and adenolymphoscintigraphy--two new diagnostic methods which allow surgeons to know preoperatively tumor extension beyond the rectal wall and lymph nodes involvement. Though the statistical data presented are not numerous, it is hoped that, using these two diagnostic methods in cases of rectal tumors, surgeons will be able to choose better between local excision and abdominoperineal resection thus avoiding unnecessary and mutilating operations.