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H Ahlman

Publications and source records attributed to H Ahlman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Intraoperative tumour detection using 111In-DTPA-D-Phe1-octreotide and a scintillation detector.

Intraoperative tumour detection has been used in many applications. The examined tumour forms have varied and different detector systems and radiopharmaceuticals have also been used. The aim of this study was to evaluate and compare the ability of an NaI(T1) scintillation detector to detect primary tumours and metastases in patients with different endocrine tumour types (e.g. carcinoid tumours, endocrine pancreatic tumours and thyroid tumours) and in patients with breast carcinoma or benign thyroid lesions, on the basis of their somatostatin receptor expression after i.v. injection of 111In-DTPA-D-Phe1-octreotide. Thirty patients were injected with 111In-DTPA-D-Phe1-octreotide intravenously. Scintigraphic images were taken 1 day after injection of the radiopharmaceutical, and surgery was performed 1-7 days post injection. An NaI(T1) scintillation detector was used for intraoperative tumour detection. Tissue samples were collected during surgery for determination of 111In activity concentration and histopathological examination. The scintigraphic images were positive in 29 out of 30 patients. Intraoperative tumour detection was successful in 43 of 66 collected biopsies: 10 out of 11 for carcinoid tumours, 7 out of 10 for medullary thyroid carcinoma (MTC) and 14 out of 22 for breast cancer. On the basis of our findings we conclude that intraoperative tumour detection with 111In-DTPA-D-Phe1-octreotide using this NaI(T1) detector can be successful especially for carcinoid tumours and endocrine pancreatic tumours, due to the relatively high activity concentrations in these tumour types, but is less successful in other forms of thyroid cancer, including MTC, and breast cancer. For successful intraoperative detection, the detector characteristics are also very important, and further improvement of the detector systems is required to increase the sensitivity and specificity.

Adolescent↗
PubMed2001

Cytotoxic treatment of adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.

Adrenal Cortex Neoplasms↗
PubMed2001

A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.

A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.

3-Iodobenzylguanidine↗
PubMed2001

Biokinetics of 111In-DTPA-D-Phe(1)-octreotide in nude mice transplanted with a human carcinoid tumor.

The long time biokinetics of the radiolabeled somatostatin analogues 111In-DTPA-D-Phe(1)-octreotide was studied in nude mice transplanted with the human carcinoid tumor, GOT1. The results were compared with those from the patient with the original tumor. This patient has been diagnosed and later treated with 111In-DTPA-D-Phe(1)-octreotide. The animals received about 2 MBq 111In-DTPA-D-Phe(1)-octreotide (0.1 microg) by injection into a tail vein. The animals were killed 0.5 h-14 d after injection of the radiopharmaceutical. Tumor tissue and normal tissues were collected and weighed and measured for 111In activity. The 111In uptake in the tumor was higher than in all normal tissues except the kidneys. The tumor-to-normal-tissue activity concentration, TNC, increased with time for all normal tissues studied. These data were similar to those observed for the original tumor in the patient. The similar biokinetics for 111In-DTPA-D-Phe(1)-octreotide in the tumor-bearing mice and the patient makes this animal model suitable as a model for evaluation of therapy of somatostatin receptor (sstr) expressing tumors with radiolabeled somatostatin analogues. Furthermore, the increase with time of TNC both in mice and the patient indicates that long-lived radionuclides are preferred for therapy with radiolabeled somatostatin analogues.

Animals↗
PubMed2001

Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome.

BACKGROUND: The association between malignant midgut carcinoid tumours and right-sided cardiac lesions is well known, but the pathogenetic link between tumour secretion and valvular disease is still obscure. The purpose of this investigation was to describe the morphological and functional changes of valvular heart disease in a large patient series and to correlate these findings with hormonal secretion and prognosis. METHODS: Of 64 consecutive patients with the midgut carcinoid syndrome followed between 1985 and 1998, valvular heart disease was evaluated in 52 patients by two-dimensional echocardiography, Doppler estimation of valvular regurgitation and flow profiles. A majority was also evaluated with exercise electrocardiography and spirometry. RESULTS: Structural and functional abnormalities of the tricuspid valve were found in 65 per cent of patients, while only 19 per cent had pulmonary valve regurgitation. Long-term survival was related to excessive urinary excretion of 5-hydroxyindole acetic acid of over 500 micromol in 24 h, but the main predictor of prognosis was the presence of severe structural and functional abnormalities of the tricuspid valve. Although advanced tricuspid abnormalities were prevalent in this series, only one patient died from right ventricular heart failure. CONCLUSION: Tricuspid valvular disease is a common manifestation of the midgut carcinoid syndrome and advanced changes are associated with poor long-term survival. Active surgical and medical therapy of the tumour disease reduced the hormonal secretion and, combined with cardiological surveillance, made right ventricular heart failure a rare cause of death in these patients.

Adult↗
PubMed2001

The gut as the largest endocrine organ in the body.

Secretin, gastrin and cholecystokinin were the first discovered gut hormones. Today we recognize more than 30 gut hormone genes and a multitude of bioactive peptides, which make the gut the largest endocrine organ in the body. Due to structural homologies gut peptide hormones/growth factors have been divided into separate families. It has been emphasized that those peptides are widely distributed, but have a specific expression in different cell types. The intestine can also be regarded as a sensory organ operating via neurons, endocrine cells and immune cells with gut peptides as signalling substances. Expression studies of peptide receptors in gut neuroendocrine tumours in combination with tailored peptide analogs have been helpful in developing new diagnostic and therapeutic strategies. New fields of research will relate to gut peptides associated with deficiency diseases and as potential growth factors in malignancies. Enterochromaffin cells, interspersed throughout the entire gastrointestinal mucosa, form the largest endocrine cell system. The physiological role of hormonal messengers, peptide receptors and amine transporters is currently under investigation as well as their potential involvement in disease, e.g. the secretory diarrhea associated with midgut carcinoid tumours.

Amines↗
PubMed2000

[Laboratory diagnosis of gastrinoma. Nordic collaboration can improve the quality].

Measurement of gastrin in serum or plasma in patients with gastrinoma may be complicated by the presence of circulating biosynthetic intermediates which may not be detected by commonly available immunoassays. In contrast, the "processing-independent analysis" of gastrins developed by professor Jens Rehfeld et al in Copenhagen detects gastrin forms irrespective of their size. The authors review gastrinoma pathophysiology, the biochemistry of gastrin and other biomarkers of gastrinoma, the differential diagnosis of hypergastrinemia as well as other methods currently employed in the workup of gastrinoma patients, and illustrate with a clinical case.

Biomarkers, Tumor↗
PubMed2000

Interventional treatment of gastrointestinal neuroendocrine tumours.

Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and endocrine pancreatic tumours) are rare diseases. In the presence of liver metastases these patients may suffer from disabling symptoms due to hormone overproduction. Patients with localized disease can be resected for cure and also patients with liver metastases can undergo potentially curative tumour resection. However, long-term follow-up of the latter cases indicates frequent recurrence of tumour. Using close biochemical monitoring of tumour markers combined with newer techniques for tumour visualization, these recurrences can often be diagnosed at an early stage so that repeat surgical procedures can be performed. During the last years very active surgery has been recommended for NE tumours, many of which have a relatively slow growth. Even in patients not amenable to curative liver surgery, debulking can be considered if the main tumour burden can be safely excised. The primary aim of this type of treatment is palliation of hormonal symptoms. An important question is whether the aggressive treatment actually prolongs survival. No prospective studies have been performed. Such studies are hampered by the lack of strict surgical programs running over long periods and the relative rarity of NE tumours. Liver transplantation may be another treatment modality in selected cases.

Biomarkers, Tumor↗
PubMed2000

Multicolor spectral karyotype analysis of a transplantable human ileal carcinoid.

In this report we present the results of a combined cytogenetic and multicolor spectral karyotype (SKY) analysis of a transplantable human ileal carcinoid (GOT1). By using SKY it was possible to identify the origin and organization of all clonal marker chromosomes and to identify cryptic translocations not detectable by conventional chromosome banding. The stemline karyotype of low passage GOT1 cells was interpreted as 43,XX, der(1)del(1)(?), inv(2)(p25q13), del(3)(p21), del(5)(q13q31), del(6)(q13), -9, -13, -15, del(16) (q22). Analysis of the GOT1 cells after about 2.5 years of propagation in nude mice allowed us to follow the in vivo progression of this tumor. Relatively few additional rearrangements had occurred during this period, indicating that the GOT1 cells are genetically stable. Most of the abnormalities detected result in loss of whole or parts of chromosomes, suggesting that loss of multiple chromosomal regions, presumably containing tumor suppressor genes, might be important genetic events in ileal carcinoids.

Animals↗
PubMed2000

111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors.

UNLABELLED: The purpose of this study was to evaluate the potential for therapy of thyroid tumors using the radiolabeled somatostatin (SS) analog octreotide. METHODS: Concentrations of 111In activity in human thyroid tumors and normal thyroid tissue and blood samples were determined 1-15 d after intravenous injection of 111In-diethylenetriaminepentaacetic acid-Phe1-octreotide. The results were compared with SS receptor (sstr subtype profile (by Northern blot analysis) and the relative expression of the second subtype, sstr2 (by ribonuclease protection assay, RPA). The true tumor volumes in lymph node metastases from 1 patient were estimated. In total, tissues from 68 patients were included in the study. RESULTS: The highest tumor-to-blood ratio (T/B) for medullary thyroid carcinoma (MTC) was 360; for follicular adenoma (FA), 190; for Hurthle cell adenoma (HCA), 140; and for Hurthle cell carcinoma (HCC) and papillary carcinoma (PC), 70. The corresponding value was 7-18 for normal thyroid tissue, with higher values for colloid goiter (8-48) and thyroiditis (7-120). A high T/B was related to a large fraction of tumor cells in lymph node metastases. T/Bs were higher for the tumor samples with expression of sstr2 at Northern blot analysis than for those without. All thyroid tumor types regularly expressed sstr1, sstr3, sstr4, and sstr5. sstr2 was expressed in most MTC tumors but was not detected in FA or PC and was irregularly expressed in HCA and HCC. However, RPA analysis detected sstr2 in all tumors studied. CONCLUSION: Despite the lack of sstr2 at Northern blot analysis in most of the thyroid tumors studied, high T/Bs were in general found when compared with corresponding values for normal thyroid tissue. The sometimes extremely high ratios are promising and indicate a possibility of using radiolabeled octreotide for radiation therapy of sstr-positive tumors in the future.

Blotting, Northern↗
PubMed1999

Altered influence of CCK-B/gastrin receptors on HDC expression in ECL cells after neoplastic transformation.

Gastrin is one of the main factors controlling enterochromaffin-like (ECL) cell endocrine function and growth. Long-standing hypergastrinemia may give rise to ECL cell carcinoids in the gastric corpus in man and in experimental models. We have analysed the expression and function of CCK-B/gastrin receptors in normal ECL cells and in ECL cell tumours (gastric carcinoids) of the African rodent Mastomys natalensis. Hypergastrinemia induced by short-term (5 days) histamine2-receptor blockade (loxtidine) resulted in increased histidine decarboxylase (HDC) mRNA expression in the gastric oxyntic mucosa. This increase was significantly and dose-dependently reversed by selective CCK-B/gastrin receptor blockade (YM022). Long-term (12 months) hypergastrinemia, induced by histamine2-receptor blockade, gave rise to ECL cell carcinoids in the gastric oxyntic mucosa. CCK-B/gastrin receptor mRNA was only slightly elevated while HDC mRNA expression was eight-fold elevated in ECL cell carcinoids and was not influenced by CCK-B/gastrin receptor blockade. Thus CCK-B/gastrin receptor blockade of hypergastrinemic animals reduces the HDC mRNA expression in normal mucosa but not in ECL cell carcinoids. These results demonstrate that HDC mRNA expression in neoplastic ECL cells is not controlled by CCK-B/gastrin receptors.

Animals↗
PubMed1999

[Nesidiodysplasia. A rare cause of hyperinsulinemia in an adult patient].

Adult hyperinsulinaemia is usually caused by benign insulinomas. These tumours are often small, and are associated with excellent outcome of surgical removal. In cases of negative outcome of surgical exploration, or of persistent hyperinsulinaemic hypoglycaemia, the possibility must be considered of some rare condition such as the presence of metastatic insulinoma, B-cell hyperplasia, multiple micro- or macro-adenomas, hyperinsulinaemia factitia, or nesidiodysplasia. The latter is the most common cause of hyperinsulinaemia in children but is rare in adults. It is defined as a maldistributed islet cell mass within the normal exocrine pancreas, with disturbed control of hormone synthesis/secretion resulting in hormone overproduction, usually hyperinsulinaemia. In persistent hyperinsulinaemic hypoglycaemia of infancy, inactivating mutations of the sulphonylurea receptor gene is one possible cause of nesidiodysplasia. Adult nesidiodysplasia is discussed in the article, and illustrated by the case of a patient undergoing distal pancreatectomy for hyperinsulinaemia, the diagnosis being subsequently established histologically. Following spleen- and duodenum-preserving subtotal (95%) pancreatectomy, the patient was symptom-free.

Adult↗
PubMed1999

[Liver transplantation in neuroendocrine tumors prolongs symptom-free period, might also be a cure].

Several neuroendocrine tumours, such as carcinoids and pancreatic endocrine tumours, may manifest relatively slow tumour growth. The patients may suffer from severe hormonal symptoms, largely due to liver metastases which sometimes are amenable to cytoreductive surgery. If residual tumour after primary tumour resection is multilobar, liver transplantation may be one way to treat hormonal symptoms and possibly prolonging survival. Early long-term outcome of liver transplantation in patients with neuroendocrine tumours suggests prognosis to be more favourable for carcinoids than for endocrine pancreatic tumours. It is suggested that liver transplantation may be appropriate for patients with isolated hepatic tumour disease in the following situations: 1, tumour recurrence after liver surgery for cure; 2, non-resectable liver disease, especially in cases of severe hormonal symptoms; and 3, disease progression after hepatic arterial embolisation and medical therapy. These indications are discussed in the light of three case reports.

Adult↗
PubMed1999

Expression of somatostatin receptors in oncocytic (Hürthle cell) neoplasia of the thyroid.

Ten consecutive patients with Hürthle cell lesions of the thyroid (nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide scintigraphy. Octreotide scintigraphy localized the primary Hürthle cell tumour in eight patients as distinct areas of increased uptake of radionuclide. Two patients with Hürthle cell carcinoma, previously thyroidectomized, had their metastases visualized by octreotide scintigraphy. Northern analyses showed expression of multiple somatostain receptor subtypes. Visualization of the Hürthle cell tumour may be due to a higher expression of somatostatin receptors in the lesions than in surrounding normal thyroid tissue. The tissue/blood (111)In concentration ratios for tumour samples from five patients showed clearly higher values than observed for normal connective tissue, muscle or lymph nodes. A relatively high uptake of (111)In was also observed in goiter tissue, which may lead to misinterpretations. The main indication for octreotide scintigraphy in patients with Hürthle cell carcinoma is suspicion of metastatic disease.

Adenoma, Oxyphilic↗
PubMed1999

Comparison of survival between malignant neuroendocrine tumours of midgut and pancreatic origin.

The survival of 64 consecutive patients with disseminated midgut carcinoid tumours was compared in a retrospective study with that of 25 consecutive patients with sporadic malignant endocrine pancreatic tumours treated according to similar surgical principles. The presence of hepatic metastases implied a worse prognosis in neuroendocrine tumours of pancreatic rather than midgut origin. This infers that these tumour types must be separated when treatments are evaluated.

Adolescent↗
PubMed1999

Involvement of serotonin and calcium channels in the intestinal fluid secretion evoked by bile salt and cholera toxin.

1. The enteric nervous system (ENS) is activated when exposing the intestinal mucosa to cholera toxin or certain bile salts. Cholera toxin stimulates ENS, at least in part, by the release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells. Calcium channel blockers of the L-type markedly attenuate the fluid secretion and the luminal release of 5-HT caused by cholera toxin. 2. The objective of the present study was to elucidate if sodium deoxycholate activated ENS in a similar manner as cholera toxin. Furthermore, the effect of several calcium channel blockers was tested on the fluid secretion caused by cholera toxin or bile salt. 3. Sodium deoxycholate (4 mM) caused a release of 5-HT into the intestinal lumen, which was inhibited by calcium channel blockade. Granisetron, a 5-HT3 receptor blocker, partly inhibited the fluid secretion caused by bile salt. 4. The effects of nifedipine, felodipine, R-felodipine, H186/86 (t-butyl analogue of felodipine) on the fluid secretion caused by cholera toxin or sodium deoxycholate were studied. Both secretory states were markedly attenuated in a dose dependent manner by all calcium channel blockers tested regardless of their effects on arterial pressure. 5. It is concluded that both cholera toxin and bile salt activate ENS, at least in part, via a release of 5-HT from the enterochromaffin cells. The antisecretory effect calcium channel blockers is partly explained by an inhibition of this release of 5-HT.

Animals↗
PubMed1999

The effects on net fluid transport of noxious stimulation of jejunal mucosa in anaesthetized rats.

A major aim of the present study was to investigate whether exposing the jejunal mucosa to a noxious stimulus induces a net fluid secretion by activating the enteric nervous system (ENS) and, if so, to what extent an axon reflex was involved. Net fluid transport was measured in vivo with a gravimetric method. The intestinal mucosa was exposed to an isotonic solution with an unphysiologically low pH (1.0). This evoked a fluid secretion, which was markedly attenuated by giving hexamethonium (nicotinic receptor antagonist) i.v. or exposing the intestinal serosa to lidocaine (local anaesthetic). Atropine (muscarinic receptor antagonist) had no effect. Luminal acid evoked a fluid secretion of the same magnitude in acutely denervated segments and in segments denervated about 3 weeks prior to the experiments. Luminal capsaicin (1.6-16 mM) did not influence jejunal net fluid transport. A second aim of the study is to investigate the effect of nifedipine (Ca channel blocker of L-type) on the acid-induced fluid secretion. Nifedipine markedly attenuated acid-induced fluid secretion. In contrast to cholera toxin-evoked secretion, the nifedipine effect was not mediated via 5 hydroxytryptamine (5-HT) as judged by measurements of 5-HT release into the intestinal lumen and the lack of effect of granisetron (5-HT3 receptor antagonist). It is concluded that the net fluid secretion evoked by hydrochloric acid in the small intestine is mainly mediated via an intramural reflex in the ENS. No experimental evidence was obtained for the involvement of an axon reflex. The site of action of the calcium channel blocker is tentatively discussed.

Anesthesia↗