Search PubMed⌕ Search

Biomedical subjects

Per Hellman

Publications and source records attributed to Per Hellman.

At least 19 recordsLinked to original sources
PubMed2006

[11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings.

CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.

Adrenal Cortex Neoplasms↗
PubMed2006

Bilateral adrenalectomy for ectopic Cushing's syndrome-discussions on technique and indication.

BACKGROUND: Tumors producing adrenocorticotropic hormone (ACTH) or corticotropin releasing hormone (CRH) often remain undiagnosed until severe Cushing's syndrome appears, and it may be difficult to distinguish from Cushing's syndrome due to pituitary tumors. Many patients suffer from disease spread, with metastases in the liver or other locations, and the main symptoms may be mineral disturbances, diabetes mellitus, or psychological symptoms from the severe hypercortisolism. Bilateral adrenalectomy may alleviate this situation, but is sometimes a troublesome procedure in these severely ill patients. METHODS: We have retrospectively investigated 8 patients with ectopic Cushing's syndrome who have undergone bilateral adrenalectomy at the University Hospital in Uppsala. In addition, another 5 patients who underwent bilateral adrenalectomy for other reasons (recurrent pituitary Mb Cushing or bilateral hyperplasia) were scrutinized for technical considerations. Indications, timing of surgery, and operative procedures were studied to identify signs that may support our approach to management in the future. RESULTS: Curative surgery was not possible in any of the cases with ectopic Cushing's syndrome. Of the 13 operated patients, handport-assisted laparoscopic adrenalectomy was successfully performed bilaterally in 5 patients and unilaterally in combination with contralateral open surgery in 1 patient; conventional open surgery was performed on 7 patients, 3 of which were conversions from intitial handport-assisted procedures. Non-fatal complications occurred in 4 out of 10 patients. CONCLUSIONS: We conclude that bilateral handport-assisted laparoscopic adrenalectomy is safe, and that all surgical techniques in these severely ill patients may be troublesome and technically demanding. Early surgical intervention may reduce the technical disadvantages. Moreover, bilateral adrenalectomy can substantially reduce the symptoms of Cushing's syndrome, although effects on mortality are not obvious.

Adrenalectomy↗
PubMed2006

Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening.

OBJECTIVE: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT) are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPT have been reported, but never in cases with normal calcium and high parathyroid hormone (PTH) levels, i.e. suffering from 'normocalcemic pHPT'. Our aim was to explore the occurrence of these metabolic abnormalities in individuals with normocalcemic pHPT identified in a population-based screening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables. DESIGN AND METHODS: A population-based screening of 5202 post-menopausal women identified 30 patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-up included 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomized setting, together with age-matched controls. Biochemical variables and body mass index (BMI) were investigated. RESULTS: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/high-density lipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides, and BMI compared to controls (P = < 0.0001-0.035). The cases had a lower HDL-cholesterol value (P = 0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx cases decreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (P = 0.0076-0.022). Investigated biochemical variables remained adverse in conservatively followed cases during follow-up except a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma. CONCLUSIONS: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMI and glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on some of these variables and reverses them to the same level as the controls, while conservative treatment fails to normalize the investigated metabolic variables.

Adenoma↗
PubMed2005

25-Hydroxyvitamin D3 1alpha-hydroxylase expression in breast cancer and use of non-1alpha-hydroxylated vitamin D analogue.

INTRODUCTION: The cytochrome P450 mitochondrial enzyme 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) of renal tubule cells hydroxylates the major circulating form of vitamin D (25(OH)D3) to the active systemic hormone 1,25(OH)2D3. Local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation. To reduce risks of hypercalcemia during treatment with vitamin D, we have previously suggested use of non-1alpha-hydroxylated vitamin D analogues to target tissues where 1alpha-hydroxylase is expressed, including the parathyroid glands in secondary hyperparathyroidism. The present study was undertaken to examine expression of 1alpha-hydroxylase in breast cancer and to investigate whether a non-1alpha-hydroxylated vitamin D analogue displayed biological function. In addition, expression of the 25-hydroxyvitamin D3 24-hydroxylase (24-hydroxylase) and the vitamin D receptor (VDR) was investigated. METHODS: The expression of 1alpha-hydroxylase, 24-hydroxylase and VDR was investigated in breast cancer specimens (n = 19) and normal breast tissues (n = 10) by immunohistochemistry and/or RT-PCR. Consecutive cryosections of 6 mum essentially free of immune cells were used in the analyses. The effect of vitamin D analogues on transcriptional activation was analyzed in transiently transfected MCF-7 breast cancer cells. RESULTS: 1alpha-hydroxylase protein was demonstrated in 79% and 100% of breast cancer specimens and normal breast, respectively. The overall relative mRNA levels of 1alpha-hydroxylase and 24-hydroxylase in normal breast compared to breast tumors were: 1alpha-hydroxylase, 1 +/- 0.07 versus 0.7 +/- 0.05, respectively (p < 0.001); 24-hydroxylase, 1 +/- 0.08 verus 2.1 +/- 0.2, respectively (p < 0.001). The VDR was expressed in 95% of the tumors as expected, with mRNA levels of 1 +/- 0.09 and 1.4 +/- 0.12 (p < 0.05) in breast cancer and normal breast, respectively. The ketoconazole-sensitive transcription activation potential of the non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089 (EB1285) was demonstrated in MCF-7 cells, which express 1alpha-hydroxylase. The activity of EB1285 was about 20% of 1,25(OH)2D3. CONCLUSION: These results demonstrate nearly normal expression levels of 1alpha-hydroxylase, 24-hydroxylase and VDR in the majority of investigated breast cancer specimens. A non-1alpha-hydroxylated vitamin D analogue displayed activity in breast cancer cells. Such analogues may present future therapeutic options for proliferative disorders where 1alpha-hydroxylase is expressed.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2005

Management of midgut carcinoids.

Midgut carcinoids developing in the small intestine represent the most common cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and fibrotic valvular heart disease. The tumours may be histologically identified with specific chromogranin A or synaptophysine immunostainings, and by serotonin reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum chromogranin A measurements are used as biochemical tumour markers for clinical diagnosis, and as important monitors of treatment effects and prognostic predictors. The midgut carcinoids have typically slow proliferation and extended disease course, and surgical treatment has become increasingly important for their management. Surgery should aim to remove primary tumours and mesenteric metastases, which may cause long-term abdominal complications, by typical fibrotic intestinal entrapment and small bowel ischaemia due to encasement of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may significantly contribute to palliation of the carcinoid syndrome. In patients with this syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues and interferon, which may alleviate symptoms and cause stable disease with slow progression. Favourable survival and life-quality can be expected with this treatment also in patients with advanced midgut carcinoids.

Balloon Occlusion↗
PubMed2005

Midgut carcinoid tumours: surgical treatment and prognosis.

Midgut carcinoids originating in the small intestine are the most common cause of the carcinoid syndrome. These tumours typically progress slowly and have an extended disease course, and although they often present with metastases at diagnosis, surgical treatment has become increasingly important for their management. Surgery should include efforts to remove mesenteric metastases, which may cause severe long-term abdominal complications with typical fibrotic intestinal entrapment and small-bowel ischaemia due to compression of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may provide considerable palliation of the carcinoid syndrome. For patients with the carcinoid syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues, which may alleviate symptoms and stabilize disease or slow progression. Favourable survival and appreciable quality of life can be expected with this combined treatment, even in patients with advanced midgut carcinoids.

Biopsy, Needle↗
PubMed2005

Pancreatic tumours as part of the MEN-1 syndrome.

Pancreaticoduodenal tumours (PETs) occur in a majority of MEN-1 patients, and have appeared as a major cause of disease-related death. Previous discussions about treatment have mainly dealt with management of various functioning tumours and clinical syndromes of hormone excess. However, hormonal syndromes often occur late with MEN-1 pancreatic tumours, and when developed indicate presence of metastases in up to 50% of the patients. Prospective screening is therefore recommended in MEN-1 with biochemical markers and endoscopic ultrasound for early detection of PETs, and early surgery before metastases have developed. Surgery is recommended in patients with or without hormonal syndromes in absence of disseminated liver metastases. The suggested operation includes enucleation of tumours in the head of the pancreas, excision of duodenal gastrinomas together with clearance of lymph node metastases, and distal 80% subtotal pancreatic resection as prophylaxis against tumour recurrence. This strategy with early and aggressive surgery is believed to reduce the risks for malignant progression.

Biopsy, Needle↗
PubMed2005

Parathyroid glands in calcium regulation and human disease.

In humans and other land-living vertebrates, the parathyroids are known to have an overall regulatory role with action as a thermostat in the systemic calcium homeostasis to ensure tight regulation of serum calcium concentrations and appropriate skeletal mineralization. Parathyroid hormone (PTH) is an 84-amino-acid peptide, synthesized and released by parathyroid chief cells in response to hypocalcemia. PTH mobilizes calcium by increasing calcium resorption from bone and by raising calcium reabsorption in the proximal kidney tubule. Treatment with active vitamin D can increase vitamin D receptor expression, inhibit growth of parathyroid tumors, and reduce PTH levels in patients with hyperparathyroidism (HPT). Newly developed vitamin D analogues with reduced calcemic effects and with more pronounced antiproliferative effect may provide new favorable treatment for reversal of HPT.

Animals↗
PubMed2004

Malignant insulinoma in ectopic pancreatic tissue.

BACKGROUND: Both ectopic pancreatic tissue and malignant insulinoma are rare. We encountered the combination of these rare entities in a patient demonstrating hypoglycemic symptoms. METHOD: A patient with episodic hypoglycemia, non-suppressed serum insulin levels, positive fasting test and a positive localization on both ultrasound and somatostatin receptor scintigraphy by (111)I-labelled octreotide, was operated and investigated. RESULTS: (111)I-labelled octreotide-guided surgery was performed and a tumor adjacent to the ligament of Treitz was extirpated. Follow-up was uneventful. Histopathology revealed a malignant insulinoma. The patient is currently under close surveillance. CONCLUSION: The rare combination of an insulinoma in ectopic pancreatic tissue, where the usual diagnostic endoscopic ultrasound revealed an extrapancreatic mass, is described. This was followed by a positive somatostatin receptor scintigraphy, enabling both radio-guided surgery and future treatment of developing recurrent disease or metastases.

Aged↗
PubMed2004

Long-term survival of patients with small intestinal carcinoid tumors.

Midgut carcinoid tumors are rare and have a markedly better prognosis than adenocarcinoma in the small intestine. New diagnostic methods and medical as well as surgical therapies have evolved during the last decades, leading to more active care of these patients. Patients with small intestinal carcinoids diagnosed from 1960 to 2000 in the duodenum (n = 89) and jejunum/ileum (n = 2437) were identified in the Swedish Cancer Registry. Cases without histologic verification and autopsy cases were excluded. Overall, cause-specific and relative survival were calculated. The overall 5-, 10-, and 15 year survivals were, respectively, 60%, 46%, and 28% for duodenal tumors and 56%, 36%, and 23% for jejunal/ileal tumors. Cause-specific 5-, 10-, and 15-year survival was 94% for all three follow-up periods for duodenal tumors and 87%, 80%, and 77% for those in the jejunum/ileum. The corresponding relative survivals were, respectively, 72%, 67%, and 51% for duodenal tumors and 67%, 54%, and 44% for those in the jejunum/ileum. Sex did not influence overall or cause-specific survival. The age at diagnosis correlated inversely with overall and cause-specific survival for tumors in the jejunum/ileum. For tumors in the jejunum/ileum, the overall and cause-specific survival correlated with the time period of diagnosis, with a more favorable prognosis for those diagnosed in recent years. A multivariate Cox proportional hazards model showed similar results. We concluded that young age and diagnosis in recent years are positive predictors of survival for patients with midgut carcinoids. The divergence between cause-specific and relative survival implies the need for a more detailed analysis of the causes of death of these patients.

Adult↗
PubMed2004

Vitamin D3 polyunsaturated side-chain analogues (EB1089, GS1590) and the 20-epi-vitamin D3 analogue CB1393 suppress parathyroid hormone secretion and mRNA level in bovine parathyroid cells.

Several vitamin D analogues, with reduced hypercalcemic and hyperphosphatemic toxicity at therapeutic dosages, are in clinical use for prevention and treatment of secondary hyperparathyroidism (HPT) in chronic renal failure. We have performed a first in vitro evaluation of five vitamin D analogues displaying less calcemic activity in normal rats, considerably more antiproliferative ability and higher transcription activation potential than 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), with the future prospects in mind to identify even more effective and less calcemic vitamin D analogues for treatment of HPT. The vitamin D analogues EB1089 and GS1590 have polyunsaturated side-chains, whereas HEP187, MC1598 and CB1393 display altered stereochemistry at carbon 20. In primary cultures of bovine parathyroid cells EB1089, GS1590, CB1393 and MC1598 as well as the comparative controls 1,25(OH)(2)D(3), 22-oxacalcitriol (OCT, maxacalcitol), 19-nor-1,25(OH)(2)D(2) (paricalcitol) and 1alpha(OH)D(2) (doxercalciferol) significantly suppressed PTH secretion or reduced PTH mRNA level at 10(-8), 10(-10), and 10(-11)M for all compounds except for MC1598 at the lowest concentration. The analogue HEP187 displayed no PTH suppressive activity. We conclude that the vitamin D analogues EB1089, GS1590 and CB1393 may be suitable for treatment of hyperparathyroidism secondary to uremia and that further evaluation in vivo should be considered.

Animals↗
PubMed2004

Primary hyperparathyroidism.

PURPOSE OF REVIEW: This contribution presents research progress concerning primary hyperparathyroidism (pHPT), and the background for recent notable changes in treatment policy. RECENT FINDINGS: Research has clarified that most patients with pHPT require surgery due to risk for osteoporosis, renal stones, and possibly silent complications of renal impairment, cardiovascular disease, and common psychiatric disability. Genetic studies have advanced, but the cause of the disease remains unclear for most patients. Localization methods for parathyroid tumors have improved and increased the interest for less invasive operative methods with shorter hospital stays and reduced costs for the patient. It is important to delineate when this really will imply progress and to use the new diagnostic methods in discussions of appropriate treatment strategies. It has also become evident that older pHPT patients especially could benefit from medical treatment of bone mineral deficit, and they may also need vitamin D or vitamin D analogues to prevent progress of the disease. SUMMARY: pHPT is a common disorder among postmenopausal women, in whom most commonly applied surgical treatment has proven markedly efficient. There is now increased interest to better understand possible causes of the disease and schedule the most efficient surgical and medical treatment and discuss possible prophylaxis.

Adult↗
PubMed2004

Surgical treatment of endocrine pancreatic tumours.

Endocrine pancreatic tumours (EPTs) are uncommon, with a major challenge to alert physicians to their recognition and requirements of treatment. Functioning EPTs cause well-known clinical syndromes of hormone excess. Insulinomas, gastrinomas and glucagonomas are most common; vipomas and somatostatinomas are rare. EPTs also occur as non-functioning lesions without symptoms of hormone excess occasionally with ectopic hormone, such as ACTH and Cushing syndrome as a late complication. The majority of EPTs are sporadic, but they may also be part of a multiple endocrine neoplasia type 1 syndrome or rarely the von Hippel-Lindau syndrome. EPTs have been of great interest to endocrine surgeons and we have, during recent years, witnessed continuing advances in diagnosis, imaging and treatment of the different tumour entities. It has become obvious that surgical treatment of these tumours is of increased concern and can have a marked impact on symptoms and survival.

Gastrointestinal Neoplasms↗
PubMed2002

Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases.

We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.

Biomarkers, Tumor↗
PubMed2002

Radiofrequency tissue ablation using cooled tip for liver metastases of endocrine tumors.

Tumors derived from hormone-producing cells are generally highly differentiated, and vast experience indicates benefit with combinations of surgical and medical treatment for metastatic disease. Tumor debulking surgery is an accepted approach for reducing hormonal symptoms and to establish better conditions for medical treatment. Radiofrequency treatment (RF), a novel method for destroying liver tumors, was used to treat 43 liver metastases in 21 patients with endocrine tumors (12 with midgut carcinoid disease; 4 with nonfunctional endocrine pancreatic tumors; 1 with a VIPoma; 1 with a glucagonoma; 1 with a gastrinoma; 2 with adrenal carcinomas). Among these patients we treated with intention to cure in 14 by RF alone or RF plus surgery. Ablation was performed either percutaneously or intraoperatively using a cooled-tip needle, applying 50 to 90 watts over 10 to 12 minutes under ultrasound guidance. Contrast-enhanced computed tomography, liver function tests, and tumor markers were followed before and after RF. There were two complications: One patient suffered from conservatively treated bile leakage, and another had pleural effusion and fever for 7 days post-RF. Two lesions developed signs of incomplete necrosis after 6 months, yielding a local recurrence rate of (4.6%). Of the 15 patients treated with curative intent, we attained cure (i.e., no residual macroscopic tumor) in 4 patients. We conclude that RF using cooled-tip needles is safe and efficient; it may be performed percutaneously and intraoperatively; and it may expand the indications for liver resection.

Adrenal Gland Neoplasms↗
PubMed2002

Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years.

OBJECTIVE: Postmenopausal women are at increased risk of primary hyperparathyroidism (pHPT). Secondary dyslipidaemia in pHPT has attracted little attention, although morbidity and mortality associated with cardiovascular diseases have been reported to be increased in these patients. DESIGN: A population-based screening programme was used to recruit postmenopausal women with mild, asymptomatic pHPT (mean serum calcium 2.57 +/- 0.12 mmol/l) and matched controls. MEASUREMENTS AND PATIENTS: Serum lipids, lipoprotein fractions and influences of treatment for the parathyroid disease were studied in 87 case-control pairs (mean age 67 years), 69 of whom completed a 5-year follow-up period. RESULTS: pHPT was characterized by decreased serum high-density lipoprotein (HDL)-cholesterol, increased total triglycerides, very-low-density lipoprotein (VLDL)-triglycerides and VLDL-cholesterol levels and an elevated atherogenic index. The differences were more pronounced in the cases with serum parathyroid hormone levels in the normal range and were inversely correlated to the serum parathyroid hormone level. Parathyroidectomy, with or without additive hormone replacement therapy, normalized the dyslipidaemia. Five-year surveillance of pHPT without treatment was associated with a maintained increase in total triglycerides and the atherogenic index and a decrease in HDL-cholesterol levels. CONCLUSION: Proatherosclerotic dyslipidaemia characterizes mild pHPT and is effectively reversed by parathyroidectomy. As dyslipidaemia might contribute to the increased risk of cardiovascular diseases and death observed in pHPT, the findings favour operative intervention rather than conservative surveillance in mild, asymptomatic pHPT in postmenopausal females.

Aged↗