Somatostatin receptor scintigraphy in patients with carcinoid tumors

In 80% to 90% of patients with carcinoids, tumor sites can be detected with [111In-DTPA-D-Phe1]-octreotide scintigraphy. Unexpected, additional localizations are reported in one-third to two-thirds of patients. In a group of 52 patients, we analyzed the results of various combinations of octreotide scintigraphy and conventional imaging. Octreotide scintigraphy, alone or in combination with other imaging modalities, led to the detection of more tumor sites than any combination of conventional imaging techniques. The combination of octreotide scintigraphy, chest radiography, and ultrasonography of the upper abdomen led to the detection of lesions in all patients in whom they could be demonstrated by any imaging means, with a sensitivity of 87% in terms of the number of detected lesions. The calculated cost for this imaging regimen was higher than for the combination of conventional imaging as applied in our group. However, the benefit was the detection of at least one lesion in 11% of patients in whom with conventional imaging no abnormalities were found. Moreover, if the results from our patient group were extrapolated to a group of 100 patients, the advantage in terms of the number of extra lesions detected would be 65 extra lesions per 100 patients. The detection of more tumor sites in patients who are known to have one tumor localization with conventional imaging may be essential when deciding whether to perform surgery. Octreotide scintigraphy can be used to localize tumors, direct the choice of medical therapy, and (expected in the near future) select patients for radiotherapy. The impact on patient management is fourfold: Octreotide scintigraphy may detect resectable tumors that would be unrecognized with conventional imaging techniques; it may prevent surgery in patients whose tumors have metastasized to a greater extent than can be detected with conventional imaging; it may direct the choice of therapy in patients with inoperable tumors; and in the future it may be used to select patients for radionuclide therapy

Clinically nonfunctioning and gonadotroph pituitary adenomas

This thesis deals with clinically nonfunctioning, ,a-subunit secreting and gonadotroph pituitary adenomas. From the literature discussed in the preceding chapter several questions arise. Below these questions are listed with a reference to where the subject concerned was mentioned or discussed in the preceding chapter, as well as with a reference to the chapter where these questions will be discussed in detail. 1. (1.2.5) Do all clinically nonfunctioning pituitary adenomas release gonadotropins and their subunits in vitro? (4,5,6) 2. (1.2.5) Can the hormone release from clinically nonfunctioning adenomas in vitro be suppressed and stimulated with hormones and drugs? (5,6) 3. ( 1. 2. 3, 1. 2. 5) Is the secretory activity of clinically nonfunctioning, a-subunit secreting, and gonadotroph adenomas better reflected in results from cell culture than in results from immunocytochemistry? (6) 4. (1.2.1,1.2.5) Are clinically nonfunctioning, a-subunit secreting, and gonadotroph pituitary adenomas to be regarded as one group? (5,6) 5. (1.2.4} Is the exaggerated response in serum gonadotropin levels to TRH limited to patients with a gonadotroph adenoma? (5) 6. (1. 2. 6) can bromocriptine significantly suppress serum gonadotropin and a-subunit concentrations in patients with a clinically nonfunctioning adenoma and will these patients benefit from prolonged treatment with bromocriptine? (5,8) 7. (1.1.2,1.2.2) By analogy with the findings in aging men, do serum estradiol concentrations decrease and gonadotropin levels increase in aging postmenopausal women? (7) 8. (1.2.6) Can GnRH analogs be beneficial in patients with gonadotroph pituitary adenomas? (8) 9. Which drugs are promising in the future treatment of gonadotroph, a-subunit secreting, and clinically nonfunctioning pituitary adenomas? (8) The major subjects discussed in the various chapters are listed below: An introduction to the literature on clinically nonfunctioning, a-subunit secreting and gonadotroph pituitary adenomas was given in Chapter 1. The presenting symptoms of these adenomas and some in vivo data are discussed in Chapter 3. confounding factors in the· in vitro research of these adenomas are analyzed in Chapter 4. The correlations between in vivo and in vitro hormone data, effects of TRH and bromocriptine, and similarities between gonadotroph and clinically nonfunctioning adenomas are discussed in Chapter 5. Additional in vitro data are presented in Chapter 6. The etiology of clinically nonfunctioning and gonadotroph adenomas is discussed in the light of the age-dependent changes in gonadotropin and sex steroid levels in normal subjects in Chapter 7. The role of 2 drugs that might be useful in the therapy of clinically nonfunctioning, a-subunit secreting and gonadotroph pituitary adenomas is discussed in Chapter a. A discussion of the major conclusions of this thesis is presented in Chapter

Somatostatin analogue scintigraphy: A simple and sensitive method for the in vivo visualization of Merkel cell tumors and their metastases

Abstract BACKGROUND: Trabecular carcinomas of the skin, or Merkel cell tumors, are aggressive neoplasms that tend to occur in sun-exposed skin. These tumors frequently metastasize and, despite therapy, the number of disease-related deaths is high. Ultrastructurally and immunocytochemically, the majority of these tumors have neuroendocrine characteristics. Recently, we described the in vivo visualization of various neuroendocrine tumors after injection of a radiolabeled somatostatin analogue (octreotide). In this study, we report the results of scintigraphy with radioactive-labeled somatostatin analogues in five patients with Merkel cell tumors. OBSERVATIONS: In all four patients in whom tumor was detected using computed tomographic scanning and ultrasound, the tumor sites were also demonstrated on octreotide scintigrams. In one patient, a tumor with a diameter that was smaller than 0.5 cm could not be detected with octreotide scintigraphy, computed tomography, or ultrasound. Using octreotide scintigraphy we found presumed tumor spots in two patients that were not evident when other techniques were used. CONCLUSIONS: Octreotide scintigraphy has an equal or even greater sensitivity than computed tomography and ultrasound for detecting Merkel cell tumors and their metastases. Establishing the spread of the disease in this way may ensure an optimal choice of treatment in patients with this type of tumor

Somatostatin receptor imaging: The presence of somatostatin receptors in rheumatoid arthritis

Objective. To investigate the in vivo and in vitro expression of somatostatin receptors (SS-R) on synovial membranes of patients with rheumatoid arthritis (RA). Methods. The joints of 14 consecutive patients with active RA, 4 patients with severe osteoarthritis (OA), and 30 control patients were studied. The somatostatin analog [111In-DTPA-D-Phe1]-octreotide was used for in vivo SS-R scintigraphy, and the somatostatin analog [125I-Tyr3]-octreotide for in vitro SS-R autoradiography. Results. Seventy-six percent (220 of 290) of the painful joints and 76% (207 of 274) of the swollen joints of the patients with RA were visualized by SS-R scintigraphy. The degree of pain and swelling correlated well with positive scintigraphy findings in the joints (P < 0.0001). In 2 of the RA patients who underwent scintigraphy, as well as in 4 of 5 other patients, in vitro studies of the synovial membranes showed the presence of specific SS-R. In patients with OA, uptake of radioactivity in the affected joints was significantly lower than that in patients with RA. None of the joints of the control patients demonstrated uptake of radioactivity. Conclusion. SS-R are present in the synovial tissue of p

Peptide receptor radionuclide therapy

Peptide receptor radionuclide therapy is a new treatment modality for patients with inoperable or metastasised neuroendocrine gastroenteropancreatic tumours. After the successful implementation of somatostatin receptor scintigraphy in daily clinical practice, the next logical step was to increase the radiation dose of the administered radiolabelled somatostatin analogue in an attempt to induce tumour shrinkage. Since then, an increasing number of patients has been successfully treated with this approach, resulting in a substantial numbers of patient with objective tumour shrinkage. Serious side-effects have been rare. This article reviews the effectiveness of the different radiolabelled somatostatin analogues used, the currently known side-effects and the survival data available. Furthermore, clinical issues, including indication and timing of therapy, are discussed. Finally, important directions for future research are briefly mentioned to illustrate that, although the currently available results already suggest a favourable outcome compared with other systemic therapies, new strategies are being developed to increase efficacy

Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma

OBJECTIVE: This study was performed to evaluate the effect of prolonged treatment with the dopamine agonist quinagolide on serum gonadotropin and alpha-subunit concentrations and tumor volume in patients with clinically non-functioning pituitary adenomas (CNPA). DESIGN: Ten patients with CNPA were treated with quinagolide (0.3 mg daily). The median duration of treatment was 57 months (range 36-93 months). Blood samples for measurement of serum gonadotropin and alpha-subunit concentrations were drawn before treatment, after 5 days, and at each outpatient visit. Computerized tomography or magnetic resonance imaging of the pituitary region and Goldmann perimetry were done before and at regular intervals during treatment. RESULTS: A significant decrease of serum FSH, LH or alpha-subunit concentrations was found in nine patients. The levels remained low during the entire treatment period. In two out of three patients with pre-existing visual field defects a slight improvement was shown during the first months of treatment, but eventually deterioration occurred in all three patients. A fourth patient developed unilateral ophthalmoplegia dur

Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

Chromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocrine markers, have not clearly been defined, however. The objectives of this study were to evaluate the clinical usefulness of CgA as neuroendocrine serum marker. Serum levels of CgA, neuron-specific enolase (NSE), and the alpha-subunit of glycoprotein hormones (alpha-SU) were determined in 211 patients with neuroendocrine tumors and 180 control subjects with nonendocrine tumors. The concentrations of CgA, NSE, and alpha-SU were elevated in 50%, 43%, and 24% of patients with neuroendocrine tumors, respectively. Serum CgA was most frequently increased in subjects with gastrinomas (100%), pheochromocytomas (89%), carcinoid tumors (80%), nonfunctioning tumors of the endocrine pancreas (69%), and medullary thyroid carcinomas (50%). The highest levels were observed in subjects with carcinoid tumors. NSE was most frequently elevated in patients with small cell lung carcinoma (74%), and alpha-SU was most frequently elevated in patients with carcinoid tumors (39%). Most subjects with elevated alpha-SU levels also had elevated CgA concentrations. A significant positive relationship was demonstrated between the tumor load and serum CgA levels (P < 0.01, by chi 2 test). Elevated concentrations of CgA, NSE, and alpha-SU were present in, respectively, 7%, 35%, and 15% of control subjects. Markedly elevated serum levels of CgA, exceeding 300 micrograms/L, were observed in only 2% of control patients (n = 3) compared to 40% of patients with neuroendocrine tumors (n = 76). We conclude that CgA is the best general neuroendocrine serum marker available. It has the highest specificity for the detection of neuroendocrine tumors compared to the other neuroendocrine markers, NSE and alpha-SU. Elevated levels are strongly correlated with tumor volume; therefore, small tumors may go undetected. Although its specificity cannot compete with that of the specific hormonal secretion products of most neuroendocrine tumors, it can have useful clinical applications in subjects with neuroendocrine tumors for whom either no marker is available or the marker is inconvenient for routine clinical use

Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro

Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst1-5, are heterogeneously expressed in the normal human thymus. This suggests their involvement in controlling the immune and/or neuroendocrine functions in this organ. Moreover, recently a high in vivo uptake of [111In-DTPA-D-Phe1]octreotide has been reporte

Enrichment of the tumour immune microenvironment in patients with desmoplastic colorectal liver metastasis

Background: Patients with resected colorectal liver metastasis (CRLM) who display only the desmoplastic histopathological growth pattern (dHGP) exhibit superior survival compared to patients with any non-desmoplastic growth (non-dHGP). The aim of this study was to compare the tumour microenvironment between dHGP and non-dHGP. Methods: The tumour microenvironment was investigated in three cohorts of chemo-naive patients surgically treated for CRLM. In cohort A semi-quantitative immunohistochemistry was performed, in cohort B intra

Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours

Background:Quality of life is an important end point in clinical trials, yet there are few quality of life questionnaires for neuroendocrine tumours.Methods:This international multicentre validation study assesses the QLQ-GINET21 Quality of Life Questionnaire in 253 patients with gastrointestinal neuroendocrine tumours. All patients were requested to complete two quality of life questionnaires - the EORTC Core Quality of Life questionnaire (QLQ-C30) and the QLQ-GINET21 - at baseline, and at 3 and 6 months post-baseline; the psychometric properties of the questionnaire were then analysed.Results:Analysis of QLQ-GINET21 scales confirmed appropriate aggregation of the items, except for treatment-related symptoms, where weight gain showed low correlation with other questions in the scale; weight gain was therefore analysed as a single item. Internal consistency of scales using Cronbach's α coefficient was >0.7 for all parts of the QLQ-GINET21 at 6 months. Intraclass correlation was >0.85 for all scales. Discriminant validity was confirmed, with values <0.70 for all scales compared with each other.Scores changed in accordance with alterations in performance status and in response to expected clinical changes after therapies. Mean scores were similar for pancreatic and other tumours.Conclusion:The QLQ-GINET21 is a valid and responsive tool for assessing quality of life in the gut, pancreas and liver neuroendocrine tumours