| 1. |
- Abrahamsson, Gun, et al.
(författare)
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Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations
- 2020
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:10, s. 1297-1302
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. Material and methods Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. Results Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [H-3]thymidine in cultured granulosa cells. Conclusions Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.
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| 2. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Adrenocortical carcinoma--diagnostic and therapeutical implications.
- 1993
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Ingår i: The European journal of surgery = Acta chirurgica. - 1102-4151. ; 159:3, s. 149-58
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the results of treatment of a consecutive series of patients with adrenocortical carcinoma who presented during the six year period 1985 to 1991.
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| 3. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Aspects on diagnosis and treatment of the foregut carcinoid syndrome.
- 1992
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Ingår i: Scandinavian journal of gastroenterology. - 0036-5521. ; 27:6, s. 459-71
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Tidskriftsartikel (refereegranskat)abstract
- Eight patients with the foregut carcinoid syndrome (two gastric and six bronchial primary tumors) are reported. The patients presented with complex clinical symptoms including ectopic production of adrenocorticotrophic hormone and growth hormone-releasing factors. The most alarming symptoms were facial flush and edema, accompanied by severe bronchoconstriction, which easily was misinterpreted as asthmatic attacks. Conventional bronchodilatory drugs may be potentially dangerous in these patients, in whom combined blockade of histamine receptors and treatment with cortisone and octreotide are recommended. Owing to the patients' age and general condition individualized long-term therapy was instituted. Surgical therapy under optimal protection by drugs can be of substantial value also in patients with advanced disease. One patient with life-threatening hormonal symptoms underwent hyperthermic perfusion of the liver with cytotoxic drugs, resulting in good palliation.
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| 4. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Clinical efficacy of octreotide scintigraphy in patients with midgut carcinoid tumours and evaluation of intraoperative scintillation detection.
- 1994
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Ingår i: The British journal of surgery. - 0007-1323. ; 81:8, s. 1144-9
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Tidskriftsartikel (refereegranskat)abstract
- 111In-diethylenetriamine penta-acetate-D-Phe1-octreotide scintigraphy was evaluated in a group of 27 patients with disseminated midgut carcinoid tumour. Additional information gained by the intraoperative use of a scintillation detector was studied in five patients with midgut carcinoid tumours and in two with endocrine pancreatic tumours. In 19 patients tumours not recognized by non-invasive radiological methods were visualized in 27 locations, most commonly in liver and para-aortic lymph nodes. Three false-negative tumour locations were noted (ovarian and peritoneal). With guidance from scintigraphic findings, nine patients underwent surgical tumour reduction, leading to complete remission in three. Clinically suspect tumour lesions were measured by the detector in situ, and ex vivo after excision. After excision the tissue:blood activity concentration ratios were calculated. In situ measurements were helpful in the localization of tumours and in the control of adequate clearance of tumour tissue. High tissue:blood activity concentration ratios at 1, 2 and 5 days in the five patients with midgut carcinoid tumour indicate a potential role for radiation therapy with radiolabelled octreotide in patients with somatostatin receptor-positive tumours.
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| 5. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Clinical management of gastric carcinoid tumors.
- 1994
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Ingår i: Digestion. - 0012-2823. ; 55 Suppl 3, s. 77-85
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Tidskriftsartikel (refereegranskat)abstract
- Four types of gastric carcinoids have been identified: (1) multiple small body-fundus carcinoids associated with chronic atrophic gastritis type A (A-CAG); (2) sporadic solitary lesions without specific pathogenetic background (non-A-CAG); (3) carcinoidosis associated with Zollinger-Ellison/MEN 1 syndrome, and (4) rare tumors, e.g. gastrin cell tumors, neuroendocrine carcinomas and mixed endocrine-exocrine tumors. In a retrospective study of 15 patients with gastric carcinoids (11 A-CAG, 3 non-A-CAG and 1 gastrin cell tumor) over a 10-year period, the histopathological and clinical features were assessed. The A-CAG-type carcinoids were clinically silent with lymph node metastases in 2/11 cases but no hepatic metastases. The non-A-CAG-type carcinoids were malignant with disseminated disease, hormonal symptoms and increased urinary excretion of the main histamine metabolite, MeImAA. Five patients with A-CAG tumors were subjected to antrectomy to remove hypergastrinemia, which is thought to be of pathogenetic importance for these tumors. During the observation period (1.5-8 years) 1 patient developed recurrent tumors, while the other 4 showed persistent argyrophil cell hyperplasia. A prospective treatment protocol of these tumors is suggested with endoscopic removal of less numerous, small lesions as first-step therapy, followed by antrectomy at recurrence. Larger lesions should be excised in combination with antrectomy. Gastrectomy is reserved for the rare cases of invasive tumors with lymph node metastases. As evident from the outcome of patients with non-A-CAG tumors radical surgery should be performed whenever practicable.
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| 6. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Cytotoxic treatment of adrenocortical carcinoma.
- 2001
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 25:7, s. 927-33
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Interventional treatment of gastrointestinal neuroendocrine tumours.
- 2000
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Ingår i: Digestion. - 0012-2823. ; 62 Suppl 1, s. 59-68
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Interventional treatment of the carcinoid syndrome
- 2004
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Ingår i: Neuroendocrinology. - 0028-3835. ; 80 Suppl 1, s. 67-73
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Tidskriftsartikel (refereegranskat)abstract
- Liver metastases imply a major problem in patients with carcinoid tumours and hormone overproduction. Patients with distant metastases can undergo resection for potential cure or for symptom palliation. In patients with bilobar liver metastases other interventions are at hand, e.g. local ablation or hepatic arterial embolization. In selected cases liver transplantation can be a treatment alternative. Prior to all interventions patients with midgut carcinoids are protected with somatostatin analogues to reduce hormone secretion. Patients with foregut carcinoids may present special problems with life-threatening release of histamine during interventions.
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| 9. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Liver transplantation for treatment of metastatic neuroendocrine tumors
- 2004
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Ingår i: Annals of the New York Academy of Sciences. - 0077-8923. ; 1014, s. 265-9
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation can be considered a therapeutic option for patients with neuroendocrine tumors only metastatic to the liver. Important selection criteria are well-differentiated tumors and a low proliferation rate (Ki67 <10%). In this series, orthopic liver transplantation offered good relief of symptoms and long disease-free intervals with initial survival of grafts and patients as in benign disease. The experience with multivisceral transplantation is still limited.
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| 10. |
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