23 results on '"Eriksson, Barbro"'
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2. Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors
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Eriksson, Barbro, Skogseid, Britt, Lundqvist, Gudmar, Wide, Leif, Wilander, Erik, and Oberg, Kjell
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Pancreatic tumors -- Prognosis ,Tumors -- Care and treatment ,Cancer -- Patient outcomes ,Endocrine gland tumors -- Prognosis ,Health - Abstract
Tumors of the hormone-secreting cells of the pancreas usually progress slowly, but can occasionally spread rapidly. About a third of these tumors do not themselves secrete hormones, but the remainder cause a variety of syndromes, depending upon the hormone secretion of the individual tumor. The patient may suffer from an insulinoma, a glucagonoma, a somatostatinoma, a gastrinoma, or the watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome. Many publications have described the clinical symptoms associated with these tumors, but there has been little discussion of the treatment, long-term follow-up, and survival of patients with endocrine pancreatic tumors (EPT). Surgery to remove the primary tumor is the backbone of treatment, but can rarely stand alone, since most patients have experienced metastatic spread at the time of diagnosis. Chemotherapy, usually consisting of streptozotocin (STZ) in combination with 5-fluorouracil or doxorubicin, produces responses in roughly 60 percent of the cases. Cures, however, are rarely achieved with chemotherapy. A review of 84 cases of endocrine pancreatic tumors revealed that 59 patients had metastatic disease, with the liver being the most common site for metastases, occurring in 51 patients. Nineteen patients received streptozotocin and 5-fluorouracil, and 11 of these responded. STZ and doxorubicin produced a response in 9 of 25 patients. Patients with WDHA syndrome and insulinomas did better than average with response rates of 62.5 and 61.5 percent, respectively; gastrinomas and nonsecreting tumors did worse at 46 and 12.5 percent. There was only one glucagonoma and one somatostatinoma in the series; neither responded to treatment. Patients with nonfunctioning tumors had a shorter survival, as well, with a median survival of 4.8 years from diagnosis. Patients with ''functioning'' tumors, that is, secreting tumors, did better, with a median survival of 14.5 years. As might be expected, survival time of patients with metastatic disease was shorter, at 6.7 years, than for patients with benign tumors, 80 percent of whom were alive after 10 years. An interesting observation on these patients was that the use of interferon, an immune system modulator, tended to increase the response rates to chemotherapy but reduce the period of time that the response lasted. The authors suggest that the growing availability of immunological assays for the pancreatic hormones should be utilized to improve detection rates of endocrine pancreatic tumors and that earlier diagnosis combined with aggressive treatment may significantly improve the chances for survival. (Consumer Summary produced by Reliance Medical Information, Inc.)
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- 1990
3. Neuroendocrine tumors with syndromic vasoactive intestinal polypeptide hypersecretion: a retrospective study
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Antonodimitrakis, Pantelis Clewemar, Olofsson, Helena, Grimelius, Lars, Sundin, Anders, Wassberg, Cecilia, Granberg, Dan, Skogseid, Britt, and Eriksson, Barbro
- Abstract
Aim:Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods:Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results:Twelve patients (67) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40 of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion:Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.
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- 2017
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4. Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours
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Crona, Joakim, Norlén, Olov, Antonodimitrakis, Pantelis, Welin, Staffan, Stålberg, Peter, and Eriksson, Barbro
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Context:As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage.Objectives:The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients.Design, Setting, and Participants:This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail.Results:In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P< .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively.Conclusion:Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course.
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- 2016
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5. Poor outcome after systemic therapy in secondary high-grade pancreatic neuroendocrine tumors
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Mollazadegan, Kazhan, Skogseid, Britt, Botling, Johan, Åkerström, Tobias, Eriksson, Barbro, Welin, Staffan, Sundin, Anders, and Crona, Joakim
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Longitudinal changes in pancreatic neuroendocrine tumor (panNET) cell proliferation correlate with fast disease progression and poor prognosis. The optimal treatment strategy for secondary panNET grade (G)3 that has progressed from a previous low- or intermediate-grade to high-grade panNET G3 is currently unknown. This was a single-center retrospective cohort study aimed to characterize treatment patterns and outcomes among patients with secondary panNET-G3. Radiological responses were assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A total of 22 patients were included and received a median of 2 (range, 1–4) treatment lines in 14 different combinations. Median overall survival (OS) was 9 months (interquartile range (IQR): 4.25–17.5). For the 15 patients who received platinum–etoposide chemotherapy, median OS was 7.5 months (IQR: 3.75–10) and median progression-free survival (PFS) was 4 months (IQR: 2.5–5.5). The 15 patients who received conventional panNET therapies achieved a median OS of 8 months (IQR: 5–16.75) and median PFS was 5.5 months (IQR: 2.75–8.25). We observed one partial response on 177Lu DOTA-TATE therapy. In conclusion, this hypothesis-generating study failed to identify any promising treatment alternatives for patients with secondary panNET-G3. This demonstrates the need for both improved biological understanding of this particular NET entity and for designing prospective studies to further assess its treatment in larger patient cohorts.
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- 2022
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6. New drugs in neuroendocrine tumors rising of new therapeutic philosophies
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Eriksson, Barbro
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There has been a major progress in the understanding of tumor biology during the past decades and, as a consequence, new potential targets for medical treatment of cancer have been identified. Some of the new so-called targeted therapies may prove to be of value also in neuroendocrine tumors (NETs). This review focuses on recent progress in the treatment of NETs, discussing new agents and also optimization/improvement of currently available therapies.
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- 2010
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7. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer
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Khan, Tanweera, Sundin, Anders, Juhlin, Claes, Wilander, Erik, Öberg, Kjell, and Eriksson, Barbro
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Abstract: The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p′-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m
2 , and vincristine, 1.5 mg/m2 , maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1–2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI’s Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.- Published
- 2004
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8. Expression of somatostatin receptor subtypes 1 to 5 in tumor tissue and intratumoral vessels in malignant endocrine pancreatic tumors
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Fjällskog, Marie-Louise, Ludvigsen, Eva, Stridsberg, Mats, Öberg, Kjell, Eriksson, Barbro, and Janson, Eva
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Abstract: Somatostatin analogs are well established in the treatment of malignant endocrine pancreatic tumors (EPTs). Our goal is to individualize their treatment using receptor-subtype-specific analogs and, therefore, exploring the receptor expression is highly important. We have examined the expression of somatostatin receptor (sst) subtypes 1–5 on tumor cells and in intratumoral vessels in 28 tumor tissues from malignant EPTs with immunohistochemistry using sst-subtype-specific polyclonal antibodies. We found that sst
2 and sst4 stained positive in 90% and sst1 in 70% of the tumor tissues, whereas sst3 and sst5 stained positive in only 50% of the tumor tissues. Sst expression in intratumoral vessels was high for sst2 and sst4 (80%), moderate for sst1 (40%), and low for sst3 and sst5 (10%). The ssts were evenly distributed among the different tumor subtypes. However, tumors belonging to the same subgroup of EPTs showed a variable expression of receptor subtypes. No differences in receptor-subtype expression could be seen between poorly and well-differentiated tumors, nor between primary tumors and metastases. Prior medical treatment did not influence sst expression pattern. In conclusion, sst2 and sst4 were expressed in most tumor tissues and intratumoral vessels from EPTs. However, sst3 and sst5 were lacking in half of the tumor tissues and in most of the intratumoral vessels. These differences indicate the importance of determining each tumor’s subset of receptors before treatment with receptor-subtype-specific analogs is initiated. The importance of sst expression in intratumoral vessels is not yet known.- Published
- 2003
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9. The Role of PET in Localization of Neuroendocrine and Adrenocortical Tumors
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ERIKSSON, BARBRO, BERGSTRÖM, MATS, SUNDIN, ANDERS, JUHLIN, CLAES, ÖRLEFORS, HÅKAN, ÖBERG, KJELL, and LÅNGSTRÖM, BENGT
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Positron emission tomography (PET) supplies a range of labeled compounds to be used for the characterization of tumor biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow up, and clinical research. The first routinely used PET tracer in oncology, 18F-labeled deoxyglucose (FDG), was successfully used for diagnosis of cancer, reflecting increased expression of glucose transporter in cancerous tissue. This tracer, however, usually does not show sufficient uptake in well-differentiated tumors such as neuroendocrine tumors. We developed a tracer more specific to neuroendocrine tumors-the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C-and demonstrated increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was so selective and the resolution was so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. To further improve the method, especially to reduce the high renal excretion of the tracer producing streaky artifacts in the area of interest, we introduced premedication by the decarboxylase inhibitor carbidopa, leading to a six-fold decreased renal excretion while the tumor uptake increased three-fold, hence improving the visualization of the tumors.
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- 2002
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10. Effect of Surgery on the Outcome of Midgut Carcinoid Disease with Lymph Node and Liver Metastases
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Hellman, Per, Lundström, Tobias, Öhrvall, Ulf, Eriksson, Barbro, Skogseid, Britt, Öberg, Kjell, Tiensuu Janson, Eva, and Åkerström, Göran
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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.
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- 2002
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11. Surgical Strategy for Large or Malignant Endocrine Pancreatic Tumors
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Hellman, Per, Andersson, Maria, Rastad, Jonas, Juhlin, Claes, Karacagil, Sadettin, Eriksson, Barbro, Skogseid, Britt, and Åkerström, Göran
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Endocrine pancreatic tumors (EPTs) are rare but have a remarkably better prognosis than adenocarcinoma of the pancreas. Patients with EPTs benefit from surgical and medical therapy, which may alleviate symptoms due to hormonal excess and increase survival. Patients with large or malignant EPTs with infiltrative disease may suffer from local complications, including gastrointestinal bleeding and obstruction and involvement of the superior mesenteric (SMV) and portal (PV) veins. Among 31 patients with operable and large or malignant EPTs, 7 had hormone-producing syndromes (insulin, glucagon), and 24 had clinically nonfunctioning EPTs. Surgery in these patients included vascular reconstruction of the SMV/PV (n= 4), resection of infiltrated adjacent organs (n= 5; stomach, transverse colon), or resection of concomitant liver metastases (n= 3). Four patients with conspicuously large insulinomas, and three with glucagonoma were successfully operated on with alleviation of hormonal symptoms. Among the 24 nonfunctioning EPTs, 5 patients had been explored earlier and their tumors judged inoperable due to locally invasive disease or misdiagnosis as pancreatic adenocarcinoma. The operations were performed with no mortality and low morbidity. We conclude that large and malignant EPTs with limited spread of disease may benefit from a combination of medical and surgical therapy.
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- 2000
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12. Method for Dissection of Mesenteric Metastases in Mid-gut Carcinoid Tumors
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Öhrvall, Ulf, Eriksson, Barbro, Juhlin, Claes, Karacagil, Sadettin, Rastad, Jonas, Hellman, Per, and Åkerström, Göran
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With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.
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- 2000
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13. Midgut Carcinoid Tumours: CT Appearance
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Sugimoto, Eiichi, Lörelius, Lars-Erik, Eriksson, Barbro, and Öberg, Kjell
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CT was performed on 80 patients referred for staging and treatment of histologically verified midgut carcinoid tumours. In 17 cases (21%) CT was normal in spite of biochemical signs of tumour (increased U-5-HIAA). The most common finding was liver metastases in 54/80 (68%) of patients. Mesenteric metastases, usually as a soft tissue mass at the mesenteric root, were found in 17/80 (21%). Retroperitoneal adenopathy was found in 19/80 (24%). During a follow-up time of 3 months to 10 years (median 3 years) 445 additional CT examinations were performed on 77 patients. In 39 of these, progressive disease (new lesions) was found after a median time of 15 months (range 3 months-6.5 years). CT is poor in detecting primary carcinoid tumours but helpful in evaluating the extent of tumour spread before surgical exploration and during follow-up once the diagnosis has been established.
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- 1995
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14. Uptake of mangafodipir trisodium in liver metastases from endocrine tumors
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Wang, Chen, Ahlström, Håkan, Eriksson, Barbro, Lönnemark, Maria, McGill, Steven, and Hemmingsson, Anders
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The purpose of the study was to investigate retrospectively whether mangafodipir trisodium (MnDPDP) can enhance the liver metastases from endocrine tumors. Thirteen patients with endocrine tumors and liver metastases underwent T1‐weighted spin‐echo (SE) and turbo gradient‐echo (GRE) MRI conducted before and 20 to 60 minutes after iv infusion of MnDPDP. Additional 24‐hour‐delay scans were performed in 8 of 13 patients. MR signal intensity (SI) was measured in liver parenchyma and metastases, which was then related to that of paraspinal muscle. A total of 30 lesions on precontrast and postcontrast images and 18 lesions on 24‐hour‐delay images were measured. An enhancement by 49% in SE and 40% in GRE images (P= .0001) was observed in tumor tissues after MnDPDP infusion. In 24‐hour‐delay images, the SI of the lesions remained relatively high, but in liver parenchyma, it decreased significantly, and the tumor‐liver tissue contrast was reduced.
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- 1998
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15. Midgut Carcinoid Tumours
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Sugimoto, Eiichi, Lörelius, Lars-Erik, Eriksson, Barbro, and Öberg, Kjell
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CT was performed on 80 patients referred for staging and treatment of histologically verified midgut carcinoid tumours. In 17 cases (21) CT was normal in spite of biochemical signs of tumour (increased U-5-HIAA). The most common finding was liver metastases in 5480 (68) of patients. Mesenteric metastases, usually as a soft tissue mass at the mesenteric root, were found in 1780 (21). Retroperitoneal adenopathy was found in 1980 (24). During a follow-up time of 3 months to 10 years (median 3 years) 445 additional CT examinations were performed on 77 patients. In 39 of these, progressive disease (new lesions) was found after a median time of 15 months (range 3 months-6.5 years). CT is poor in detecting primary carcinoid tumours but helpful in evaluating the extent of tumour spread before surgical exploration and during follow-up once the diagnosis has been established.
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- 1995
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16. Limited Tumor Involvement Found at Multiple Endocrine Neoplasia Type I Pancreatic Exploration: Can It Be Predicted by Preoperative Tumor Localization?
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Skogseid, Britt, Öberg, Kjell, Åkerström, Göran, Eriksson, Barbro, Westlin, Jan-Erik, Janson, Eva Tiensuu, Eklöf, Hampus, Elvin M.D., Anders, Juhlin, Claes, and Rastad, Jonas
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Abstract. Radiologically demonstrable pancreatic endocrine tumors are a frequent requirement for exploration in patients with multiple endocrine neoplasia type I (MEN-I). Such delayed intervention is accompanied by a 30% to 50% incidence of pancreatic endocrine metastases. This study explores biochemical tumor markers and operative findings in relation to preoperative pancreatic radiology in 25 MEN-I patients. They underwent pancreatic surgery with (: n = 19) or without ( n = 6) radiologic signs of primary tumor and absence of metastases upon conventional examination, including OctreoScan testing ( n = 10). Biochemical diagnosis required an increasing elevation of at least two independent pancreatic tumor markers. Tumor diameters averaged 1.1 cm (0–5 cm) and 0.9 cm (0.2–1.5 cm) in the patients with and without positive preoperative radiology, respectively. These investigations never displayed more than one of the consistently multiple tumors, and the results were falsely positive in 26%. Preoperatively unidentified regional or hepatic metastases were found at surgical exploration in 26% of patients with radiologic localization and in none of the others. Limited pancreatic tumor involvement necessitated intraoperative absence of metastases and pancreatic lesions ≤ 1 cm in diameter on palpation, intraoperative ultrasonography, and microscopy. It occurred in 37% and 50% of the patients with and without radiologic tumor localization, respectively. The number of positive tumor markers was similar for patients with limited and major disease (2.3 vs. 2.7), whereas four or more such markers were found in all those with malignancies. The mean marker level was higher in patients with radiologically demonstrable tumors and lower in those with limited disease, but with a substantial overlap. OctreoScan testing was negative in all cases with limited disease and was the single most sensitive method (75%) in the others. Limited pancreatic disease could not be identified preoperatively, and the present means of biochemical pancreatic tumor identification invariably involved the presence of at least one lesion ≥ 7 mm in diameter. Conventional pancreatic imaging is insensitive and nonspecific for recognizing even substantial pancreatic tumors associated with MEN-I.
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- 1998
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17. Selective effects of somatostatin analogs on human drug-metabolizing enzymes*
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Rasmussen, Eva, Eriksson, Barbro, Öberg, Kjell, Bondesson, Ulf, and Rane, Anders
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Pharmacologic or surgical manipulation with growth hormone secretion or with the physiologic release of somatostatin and growth hormone-releasing hormone affects some rat liver enzymes, especially the sex-differentiated ones. We investigated the effects of two somatostatin analogs on several enzyme functions in six patients with carcinoid syndrome, using codeine as a probe drug. Codeine was given intravenously and its N- and O-demethylation, as well as 6-glucuronidation catalyzed by CYP3A, CYP2D6, and uridine diphosphate-glucuronosyltransferase, respectively, were studied before and during treatment with somatostatins. After 3 days of treatment with somatostatins the partial metabolic clearance of codeine by N-demethylation decreased by 21% to 64% in all patients (mean change, 44%; p < 0.05), and the clearance by O-demethylation was decreased by 20% to 69% in five of the patients (mean change in all patients, 35%; p < 0.05). In contrast, the partial clearance by 6-glucuronidation and the total systemic clearance of codeine were unchanged. Our results may be caused by the inhibition of growth hormone secretion induced by the somatostatins, inasmuch as direct metabolic interactions with these peptide drugs are improbable. The decline in CYP3A4 and CYP2D6 activity might have clinical implications when substrates of these enzymes with low therapeutic indices are combined with somatostatin analogs. Because the formation of morphine from codeine was altered, the analgesic effect of this drug may be reduced during concomitant treatment with somatostatins.
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- 1998
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18. Induction of Apoptosis in Neuroendocrine Tumors of the Digestive System During Treatment with Somatostatin Analogs
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Imam, Hassan, Eriksson, Barbro, Lukinius, Agneta, Janson, Eva, Lindgren, Per-Gunnar, Wilander, Erik, and Öberg, Kjell
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The extent of apoptosis identified by in situ DNA nick end labelling (TUNEL) on tissue samples obtained from patients with neuroendocrine tumors was correlated with the clinical outcome in patients treated with high-dose somatostatin analog (lanreotide 12 mg/day), n = 8, or other biotherapy including interferon-alpha (IFN-α), n = 4, low-dose somatostatin analog (octreotide or lanreotide), n = 3, or a combination of both, n = 1. Biopsies were obtained before the start of treatment and/or after 6 months and 12 months. After 6 months of treatment, 5 patients receiving high-dose somatostatin analog showed a biochemical response (decrease in different neuroendocrine tumor markers) and 4 of these showed an increase in apoptotic index (AI: percentage of apoptotic cells) by 1.94 ± 1.71%. At 12 months, AI was also increased in patients with a biochemical response (4.22 ± 3.93%). However, none showed a decrease in tumor size on computerized tomography (CT) and none of the patients treated with low-dose somatostatin analog or IFN-α showed any significant increase in AI during treatment. In an experimental model, nude mice were xenografted with the neuroendocrine cell line (BON-I). From the 2nd day of tumor implantation, they treatment with either placebo, high-dose octreotide, IFN-α, or a combination of both, for 28 days. In mice receiving treatment with high-dose octreotide (300 μg/kg, t.i.d) there was a threefold increase in apoptotic cells as compared to the placebo group (p = 0.0084), while the combination group had few cells with ultra-structural changes indicating apoptosis and the IFN-α treated group showed no significant changes. However, tumor growth inhibition was more pronounced in the combination group (p = 0.0011). This probably denotes that tumor growth inhibition could be achieved more efficiently by blocking the cell cycle than by inducing apoptosis. We concluded that treatment with high-dose somatostatin analogs may induce apoptosis in neuroendocrine tumors, while this is not found during treatment with low-dose somatostatin analogs or IFN-α. We also found that an increase in AI during high-dose somatostatin analog treatment was correlated with the biochemical response, but not with the tumor size as detected by CT in patients or with the tumor mass in the experimental model.
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- 1997
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19. An Update of the Medical Treatment of Malignant Endocrine Pancreatic Tumors
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Eriksson, Barbro and Öberg, Kjell
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In the present study, we have updated our results with chemotherapy, a-interferon, octreotide and combinations of treatment modalities in patients with malignant endocrine pancreatic tumor (EPT). In our patient material of 134 EPT, 92 subjects had malignant tumors as evidenced by the presence of metastases or growth into adjacent organs. Seventy-eight patients had liver metastases. Streptozotocin plus 5-fluorouracil produced objective responses in 17/31 (54%) patients with a median duration of response of 23 months. The use of 5-HT3-antagonists as antiemetics has dramatically improved the quality of life during treatment by reducing the frequency of nausea to only 12.5%. The objective response rate to α-interferon (a-IFN) treatment, given as first-line treatment in 29 patients and after chemotherapy in 28 patients, was 51% (29/57) with a median duration of response of 20 months. Octreotide, which is still used as third-line treatment in most patients, produced significant biochemical responses in 6/19 (31%) patients with a median duration of 16 months. Combinations of α-IFN plus chemotherapy and a α-IFN plus octreotide in a small number of patients might indicate additive or synergistic effects. The median survival from start of treatment in the 92 malignant cases was 56.5 months, and for those with liver metastases (n = 78) at start of treatment 50 months. In conclusion, there are at least three effective therapies for malignant EPT and by combining them simultaneously or consecutively, a median survival of more than four years can be obtained.
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- 1993
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20. Positron Emission Tomography (PET) in Neuroendocrine Gastrointestinal Tumors
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Eriksson, Barbro, Bergström, Mats, Lilja, Anders, Ahlström, Håkan, Långström, Bengt, and Öberg, Kjell
- Abstract
Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
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- 1993
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21. Excision biopsy of the spleen by ultrasonic guidance
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Lindgren, Per G., Hagberg, Hans, Eriksson, Barbro, Glimelius, Bengt, Magnusson, Anders, and Sundström, Christer
- Abstract
Excision biopsy of the spleen was performed in 32 patients, using a recently invented instrument, which consists of a spring-trigger system for firing the two parts of a Tru-Cut needle. The biopsies were carried out under the guidance of an ultrasonic scanner. This technique yields sufficient material of high quality for a proper evaluation both of individual cells and the internal structure of the spleen. Eight patients had parenchymal abnormalities found by ultrasonic scanning: five had multiple abnormalities whereas three had a single abnormal area. Seven of these eight patients had a pathological spleen biopsy, consisting of Hodgkin's disease (four patients), “high-grade” malignant non-Hodgkin's lymphoma (two patients) or tuberculosis (one patient).In the other 24 patients with a normal ultrasonic picture of the splenic parenchyma five biopsies were pathological (3 cases of hairy-cell leukaemia, 1 of Gaucher's disease and I of Hodgkin's disease). Side-effects were: slight to moderate pain 16/32 patients) and bleeding requiring transfusion (4/32 patients). In one of these patients splenectomy was performed because of the bleeding. Two of the patients with bleeding complications suffered from hairy-cell leukaemia. It is concluded from this study that excision biopsy of the spleen is a diagnostic method which in some patients can replace splenectomy. The method seems to be valuable especially in patients with parenchymal abnormalities shown by ultrasonic scanning.
- Published
- 1985
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22. [111In-DTPA-D-Phe1]Octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment
- Author
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Janson, Eva Tiensuu, Westlin, Jan-Erik, Eriksson, Barbro, Ahlström, Håkan, Nilsson, Sten, and Öberg, Kjell
- Abstract
Tiensuu Janson E, Westlin J-E, Eriksson B, Ahlström H, Nilsson S, Öberg K. [111In-DTPA-D-Phe1]Octrotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 1994:131:577–81. ISSN 0804–4643This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy: of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication.Eva Tiensuu Janson, Dept of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden
- Published
- 1994
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23. Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma
- Author
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Gröndal, Staffan, Eriksson, Barbro, Hagenäs, Lars, Werner, Sigbritt, and Curstedt, Tore
- Abstract
The urinary steroid profile was determined in 24 patients with adrenocortical carcinoma. Seventeen of the patients had Cushing's syndrome, virilization or feminization, and 7 had no signs of endocrine disease. Seven of the 11 patients still alive are free of disease, after a follow-up period of 5-75 months. The steroid profile varied widely between the patients with adrenocortical carcinoma. Patients with Cushing's syndrome had increased levels of cortisol metabolites and those with virilism had raised excretion of androgen metabolites. Six of the patients with adrenocortical carcinoma showed normal values of these metabolites. In 23 of the 24 patients the excretion of 3β-hydroxy-5-ene steroids and/or metabolites of cortisol precursors, such as tetrahydro-11-deoxycortisol, were significantly increased, compared with healthy controls or patients with adrenal adenomas. These findings suggest a relative deficit or low activity of 3β-hydroxysteroid dehydrogenase/Δ5-4isomerase and/or 1 1β-hydroxylase in tumour tissue. In the single patient where the steroid profile failed to indicate malignancy, hypercortisolism was seen and the tumour mass was small. The steroid excretion normalized after radical surgery and decreased in patients responding to chemotherapy. During recurred disease the metabolites of 3β-hydroxy-5-ene steroids and/or cortisol precursors increased, but in some patients the excretory pattern then was different from that seen before treatment.
- Published
- 1990
- Full Text
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