| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
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| 5. |
- Dindelegan, G., et al.
(författare)
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Accelerated acute rejection of the intestinal graft in CD28-deficient mice.
- 2007
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 37:1, s. 82-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Multiple in vivo studies have shown that the pace and severity of graft rejection is little or not at all changed by deleting CD28 molecules in the recipient. These findings contrast with the effects of monoclonal antibody therapy aimed the same costimulatory target. The objective of the present study was to evaluate how the acute rejection process is affected in CD28-deficient mice using a fully allogeneic, highly immunologically reactive transplant model. METHODS: Heterotopic vascularized small bowel transplants were performed in 24 recipient mice divided into 4 groups: 2 wild-type and 2 knockout groups. Each group consisted of 5 to 7 animals in which BalbC mice were used as intestinal donors to either wild-type C57BL6 or C57BL6 background CD28-deficient recipient mice. Selected endpoints were 3 and 6 postoperative days (POD). Intestinal rejection was evaluated by mucosal laser Doppler flowmetry (expressed in perfusion units) and histology (expressed in rejection grades). RESULTS: Acute rejection occurred in both wild-type and CD28-deficient groups. At POD 3, no significant difference was noted between groups in terms of mucosal perfusion and histology. At POD 6, significant differences in graft mucosal perfusion and histology revealed a more aggressive rejection in the CD28-deficient group compared to the wild-type group. CONCLUSIONS: The present study showed that the severity of intestinal graft rejection responses was amplified by deleting CD28 molecules. Together with data from other studies, these results suggest a different pattern of distribution and/or activation of CD28/B7 receptors in various organs.
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| 6. |
- Olausson, Michael, 1956, et al.
(författare)
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Indications and results of liver transplantation in patients with neuroendocrine tumors.
- 2002
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 26:8, s. 998-1004
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Tidskriftsartikel (refereegranskat)abstract
- Metastases from neuroendocrine (NE) tumors of the gastrointestinal tract, carcinoids, and endocrine pancreatic tumors (EPTs) can be confined to the liver for long periods and may exhibit slow growth. When considering liver transplantation (LTx) for patients with NE tumors, the expected results with conventional treatment must be weighed against the risk of LTx and immunosuppression. The following indications for LTx may be considered for patients with metastatic NE tumors limited to the liver: (1) tumors not accessible to curative surgery or major tumor reduction; (2) tumors not responding to medical or interventional treatment; and (3) tumors causing life-threatening hormonal symptoms. We excluded patients with poorly differentiated NE carcinoma or well differentiated NE carcinoma with a high proliferation index (Ki 67 > 10%). Over 4 years (1997-2001) we have performed transplants in nine patients (five with EPTs, four with carcinoids) with a mean +/- SEM follow-up of 22 +/- 5 months (range 4-45 months). Seven patients underwent orthotopic LTx and two multivisceral LTx. Eight patients are alive, six without clinical evidence of disease. Four patients developed recurrent tumors 9 to 36 months after LTx; two were detected at an early stage and underwent resection with curative intent. One patient with multivisceral Tx died after 4 months of posttransplant lymphoproliferative disease without tumor recurrence. In selected series LTx can offer good control of hormonal symptoms, a relatively long disease-free interval, and in individual cases potential cure.
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| 7. |
- Olausson, Michael, 1956, et al.
(författare)
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[Liver transplantation in neuroendocrine tumors prolongs symptom-free period, might also be a cure]. : Levertransplantation vid neuroendokrina tumörer. Ger längre tids symtomfrihet, kanske även bot.
- 1999
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Ingår i: Läkartidningen. - 0023-7205. ; 96:36, s. 3783-6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Olausson, Michael, 1956, et al.
(författare)
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Orthotopic liver or multivisceral transplantation as treatment of metastatic neuroendocrine tumors
- 2007
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Ingår i: Liver transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1527-6465 .- 1527-6473. ; 13:3, s. 327-33
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Tidskriftsartikel (refereegranskat)abstract
- Liver transplantation can be a therapeutic option for individual patients with neuroendocrine tumors metastatic only to the liver. In this consecutive series of 15 patients (5 multivisceral and 10 orthotopic liver transplantations) with well-differentiated carcinoids, or endocrine pancreatic tumors, we allowed higher proliferation rate (Ki67 <10%), large tumor burden, and higher age than previous studies. Liver transplantation offered good relief of symptoms, long disease-free intervals, and potential cure in individual patients. The survival of grafts and patients compared well with transplantation for benign disease. The overall 5-year survival was 90%. The recurrence-free survival of both multivisceral and liver transplantation related to the time after transplantation (about 20% at 5 years) despite inclusion of patients with higher risk. In conclusion, the critical prognosticators for long-term outcome still remain to be defined. The experience with multivisceral transplantation for patients with endocrine tumors of the pancreatic head is still limited.
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| 9. |
- Oltean, Mihai, 1976, et al.
(författare)
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Intragraft heat shock protein-60 expression after small bowel transplantation in the mouse.
- 2004
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 36:2, s. 350-2
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Tidskriftsartikel (refereegranskat)abstract
- The time course of heat shock protein 60 (hsp 60) expression after intestinal transplantation in syngeneic and allogeneic combination was correlated with the degree of rejection. Hsp 60 expression was assessed by immunostaining; rejection degree was established by histologic examination on posttransplantation days 1, 3, 6, and 8. No signs of rejection occurred in syngeneic grafts at any time. In the allogeneic setting, rejection was absent in all but 1 case on postoperative day 3. Three days later moderate rejection was evident based on focal crypt destruction and focal mucosal ulceration, whereas at postoperative day 8 extensive mucosal sloughing was the dominant feature, consistent with advanced rejection. Hsp 60 remained undetectable in the syngeneic setting at all times. In allografts, hsp 60 was initially expressed on posttransplant day 3, increasing synchronously with the progression of rejection at days 6 and 8. Hsp 60 expression was localized almost exclusively to the crypt area and the lower third of the villi. In conclusion, the rejection of murine allogeneic intestinal grafts is characterized by a progressive expression of hsp 60 in the epithelium.
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| 10. |
- Oltean, Mihai, 1976, et al.
(författare)
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Laser-Doppler flowmetry in the monitoring of the human intestinal allograft: a preliminary report.
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:6, s. 1723-5
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Tidskriftsartikel (refereegranskat)abstract
- During acute rejection, graft endothelium becomes a prime target for recipient immune cells. Animal studies have shown reduced microvascular perfusion, probably due to increased endothelial-leukocyte interaction and endothelial impairment, leading to graft damage. Using laser-Doppler flowmetry (LDF), we correlated the microvascular blood flow in the intestinal mucosa of five patients receiving multivisceral grafts with clinical events and pathology results. Measurements (n = 75) were performed during the first 4 weeks posttransplantation by inserting the LDF flexible probe through the ileostomy for 25 to 30 cm. Forty-six of the 75 measurements were performed within 24 hours of endoscopy and biopsy. In uncomplicated cases, we recorded a gradual increase in mucosal perfusion during the first week posttransplantation that presumably reflected regeneration after reperfusion injury. Increased mucosal perfusion did not seem to correlate with rejection or other adverse clinical events. Sudden and sustained decreases in mucosal perfusion by 30% or more compared to the previous measurements were associated with septic episodes, rejection, or both. LDF revealed a good sensitivity in monitoring the intestinal microcirculation. It was able to indicate perfusion changes associated with acute rejection. The relatively low specificity of LDF may be compensated by the low invasivity, allowing frequent investigation. LDF may be an additional tool for routine monitoring of intestinal allografts.
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