| 1. |
- 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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| 2. |
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| 3. |
- Ben-Shabat, Ilan, et al.
(författare)
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Isolated hepatic perfusion as a treatment for liver metastases of uveal melanoma.
- 2015
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Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :95
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Tidskriftsartikel (refereegranskat)abstract
- Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation. In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.
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| 4. |
- Cahlin, Christian, 1959
(författare)
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Cyclooxygenase activity and tumor progression
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Invasive growth of malignant tumors is associated with local and systemic inflammation, which may promote progression and metastases. Inflammation is also responsible for appearing manifestations of advanced cancer as fatigue, anorexia and wasting with eicosanoids, proinflammatory cytokines and nitric oxide as mediators. The aim of the present work was to extend information on the significance of cyclooxygenase activity in local and systemic progression of tumor disease. Methods: Murine tumor models (MCG-101, K1735-M2), human carcinomas xenontransplanted to nude mice, tumor cell cultures and tissue samples from human colorectal adenocarcinomas were used. Inhibitors of cyclooxygenase and nitric oxide synthase, antibodies against IL-6 and recombinant IL-12 were used to evaluate effects on tumor growth, inflammation (SAP, CRP, ESR) and host wasting (anorexia, body composition). Expression of proteins was evaluated by immunohistochemistry, western blot and RT-PCR. Signal molecules were quantified by RIA, ELISA and immunoelectrophoresis. Eicosanoids and polyamines were fractionated by HPLC. Cell proliferation was estimated by mitotic counting and flow cytometry. Results: Inhibition of prostaglandin synthesis (indomethacin) reduced tumor growth, attenuated host wasting and prolonged survival in MCG-101 bearing mice with high tumor production of PGE2. By contrast, no such effects were seen in K1735-M2 bearing mice with insignificant PGE2 production. Indomethacin also reduced growth of human tumors on nude mice. There was no clear-cut correlation between overall COX-2 expression in tumors and sensitivity to indomethacin treatment, although COX-2 expression was significantly correlated to tumor PGE2 production; factors that predicted reduced survival in colon carcinoma. IL-6 deficient mice showed reduced tumor growth and wasting. Indomethacin reduced plasma PGE2 levels and wasting in all groups of cytokine knockout mice, but only IL-12 knockouts showed concomitant reduction in tumor growth. Recombinant IL-12 reduced tumor growth in wild type mice, but not so in IFN-? deficient mice. Cytokine knockout tumor-bearing mice experienced anorexia to the same extent as wild types. Our results suggested subtype EP receptors to explain effects by PGE2 exposure to tumor and stroma cells. Systemic inflammation was related to tumor cell proliferation evaluated by p15, TGFb3 and Bcl-2 in tumor tissue. Indomethacin treatment increased tumor tissue expression of IL-6, TNF-?, GM-CSF, TGF?, cNOS decreased expression of b-FGF, angiogenin, vWF and blood vessel density, whereas EGF, VEGF, PDGF A, B, IL-1?, transferrin receptors were unchanged. Cell cycle was prolonged in vivo but not in vitro by indomethacin. NSAID inhibition of tumor growth and host-wasting was not simply related to COX specificity. NOS-inhibitors reduced tumor growth in both MCG-101 and K1735-M2 tumors expressing high amounts of cNOS and iNOS. Synergism between COX- and NOS-inhibition was not observed. NOS inhibition attenuated host wasting to the same extent as indomethacin in MCG-101 bearing mice. Conclusion: Results in the present study demonstrate that cyclooxygenase activity is central in tumor progression with well-recognized host stigmata of systemic inflammation both in experimental and clinical cancer. Such effects are connected to classic tumor growth factors, cytokines and nitric oxide, where redundancy among cytokines was pronounced in development of host deteriorations (cachexia).
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| 5. |
- Cahlin, Christian, 1959, et al.
(författare)
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Growth associated proteins in tumor cells and stroma related to disease progression of colon cancer accounting for tumor tissue PGE2 content.
- 2008
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Ingår i: International journal of oncology. - 1019-6439. ; 32:4, s. 909-18
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Tidskriftsartikel (refereegranskat)abstract
- Connections among specific proteins (Bax, Bcl-2, bFGF, COX-1, COX-2, E-cad, p15, p53, PCNA, TGFbeta3, TUNEL, vWF) in control of cell proliferation, apoptosis, cell adhesion, tumor vascularity and PGE2 content were evaluated in colon cancer as related to disease progression and survival. Tumor tissue and adjacent normal colon mucosa were obtained at curative resection in 22 patients. PGE2 concentrations were assessed in tumor tissue and tumor derived blood, splanchnic blood, peripheral venous blood and urine. Host inflammation was determined (CRP, ESR) in relationship to tumor differentiation and stage. Patients survived as expected according to Dukes A-D staging. Growth-related proteins correlated between tumor cells and stroma as well as between protein factors within tumor cells and tumor stroma. COX-2 predicted tumor tissue content of PGE2 (p<0.002), without reflection in tumor derived blood. Systemic inflammation was predicted by p15, TGFbeta3 and Bcl-2 in tumor tissue (p<0.001). p15 and vWF predicted reduced survival in ungrouped patients (p<0.02), while p15, PCNA, TGFbeta3 and vWF predicted reduced survival (p<0.0001) when patient grouping accounted for high tumor content of PGE2. Our results connect systemic inflammation and survival to COX-2 staining and increased PGE2 in colon cancer. Thus, it seems important to understand proximal signals behind upregulation of COX-2 and subsequent PGE2 production in certain tumor cells in colon cancer.
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| 6. |
- Cahlin, Christian, 1959, et al.
(författare)
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The effects of non-selective, preferential-selective and selective COX-inhibitors on the growth of experimental and human tumors in mice related to prostanoid receptors
- 2005
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Ingår i: International journal of oncology. - 1019-6439. ; 27:4, s. 913-23
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Tidskriftsartikel (refereegranskat)abstract
- Earlier observations on cyclo-oxygenase inhibitors (NSAIDs) restricting tumor growth were re-evaluated by comparing the effects of non-selective, preferential selective and selective derivatives of COX-inhibitors on tumor growth in mouse models with either prostaglandin-sensitive (MCG-101, human tumors) and -insensitive transplants (K1735-M2). Tumor growth, with and without provision of a classical cyclo-oxygenase inhibitor (indomethacin), was related to tumor content of COX-1/COX-2 protein as well as to EP1-EP4 and prostacyclin receptor expression. Mouse serum amyloid protein (SAP) was measured as an indicator of systemic inflammation, which relates to pro-inflammatory cytokines. Indomethacin inhibited tumor growth and prolonged the survival of mice bearing MCG-101 tumors, which display a high production of PGE2, while K1735-M2 tumors with insignificant amounts of PGE2 did not respond to indomethacin at all. However, the effects of various NSAIDs on tumor growth were highly variable in combination with the fact that most preferential selective and selective COX-2 inhibitors attenuated poorly systemic inflammation evaluated by plasma concentrations of mouse SAP. The ability of NSAIDs to attenuate tumor growth was not related to the tumor content of COX-2 protein as expected. Multivariate analysis suggests that significant COX-inhibition of tumor growth may be related to tumor expression of subtype EP2, EP3 (p<0.005) and perhaps EP4 (p<0.09) in complex interplay. The extent of tumor growth inhibition by COX-inhibitors is not simply related to drug specificity on COX-1 or COX-2 pathways. Such effects may instead be related to tumor expression of prostanoid receptors in tumor tissue.
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| 7. |
- Lindnér, Per, 1956, et al.
(författare)
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Extended right-sided liver resection for colorectal liver metastases--impact of percutaneous portal venous embolisation
- 2006
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Ingår i: European journal of surgical oncology. - 0748-7983. ; 32:3, s. 292-6
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare the outcome after extended right liver lobe resection (ERL) for patients with liver metastases from colorectal cancer with preceding portal vein embolisation (PVE) with a non-PVE-group. METHODS: Nineteen patients underwent ERL (resection of segment 4-8) for colorectal liver metastases after PVE. They were compared with 21 patients that underwent an ERL without embolisation. A comparison was made with 84 patients undergoing right lobe liver resection during the same time period. Survival, post-operative morbidity and mortality were recorded and the volume of the future remnant liver (FRL) was measured with CT. RESULTS: There were major complications in 1/19 patients in the PVE-group and in 6/21 in the non-PVE-group (p=0.04). No post-operative deaths were observed in the PVE-group, compared to three deaths in the non-PVE-group (p=0.09). The median survival in the PVE-group was 32 months, which did not differ from the non-PVE-group. In 21% of the patients that underwent PVE, progression occurred during the time between embolisation and surgery. There was no difference in survival for patients that underwent PVE followed by ERL, compared to patients that underwent standard right lobe liver resection. CONCLUSION: The survival of patients after ERL is comparable with patients that undergo standard right lobe resection and have less liver tumour.
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| 8. |
- Lönnroth, Christina, 1946, et al.
(författare)
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Effects related to indomethacin prolonged survival and decreased tumor-growth in a mouse-tumor model with cytokine dependent cancer cachexia.
- 1995
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Ingår i: International journal of oncology. - 1019-6439. ; 7:6, s. 1405-13
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-bearing mice with two different locally growing malignant tumors (epithelial like, MCG 101; malignant melanoma, K1735-M2) were used to evaluate the putative role of prostaglandins for survival and local tumor growth in experimental cancer. Daily systemic injections of indomethacin (1 mu g/g bw) were used to block prostaglandin production in normal and T-cell deficient tumor-bearing nude mice. Tumor progression was determined by measurements of tumor weight, DNA-synthesis, cell cycle kinetics in vivo and in vitro (flow cytometry), tumor tissue concentrations of polyamines (putrescine, spermidine, spermine) and tumor tissue gene expression of growth regulating factors (IL-1 alpha, IL-6, TNF alpha, A,B-PDGF, EGF, VEGF, bFGF, TGF beta(3), angiogenin and transferrin receptor). Tumor tissue content of von Willebrandt factor VIII was estimated by immunohistochemistry. Indomethacin had no effect on survival, host nutritional state or local tumor growth in mice bearing the malignant melanoma with low PGE(2) production. In contrast, indomethacin prolonged survival, improved cachexia and decreased tumor growth in mice bearing the MCG 101 tumor with hundredfold higher prostaglandin tumor production, leading to elevated liver and muscle tissue as well as plasma concentrations of PGE(2). Indomethacin inhibited almost completely the high tumor PGE(2) production in MCG tumors, leading to prolonged potential doubling time for tumor growth in vivo, and a trend to decreased tumor tissue concentration of polyamines (spermidine). Indomethacin had no inhibitory effect on tumor cell proliferation in vitro, although PGE(2) production was decreased by 75%. The effect of indomethacin in vivo was independent of T-cells and was observed with similar magnitude irrespective of the number of MCG cells (10(4)-10(6)) implanted or the site of implantation (s.c., i.p., liver, lung, skeletal muscles). Tumor growth inhibition by indomethacin was not intrinsically transferable by tumor cells from indomethacin treated tumor-animals. Tumor expression of mRNA for several growth regulating factors were either increased (IL-6, TNF alpha, GM-CSF, TGF beta(3)) unchanged (EGF, VEGF, PDGF A,B, IL-1 alpha, transferrin receptor) or decreased (b-FGF and angiogenin) (p<0.05) by indomethacin treatment of MCG mice. Decreased tumor content of von Willebrandt factor VIII in combination with an attenuated tumor vasculature were associated with decreased tumor growth (p<0.05). Our results confirm that high tumor production of prostaglandins was related to reduced survival. Tumor prostaglandins probably promote local tumor growth by stimulation of tumor surrounding cells to produce growth factor(s) for tumor angiogenesis including tumor and matrix cell proliferation unrelated to immune cells.
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| 9. |
- 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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| 10. |
- 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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| 11. |
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| 12. |
- Olofsson Bagge, Roger, et al.
(författare)
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Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases : A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
- 2023
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 3042-3050
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: About half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODS: In this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTS: Ninety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSION: IHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
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| 13. |
- Olofsson Bagge, Roger, 1978, et al.
(författare)
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Isolated Hepatic Perfusion With Melphalan for Patients With Isolated Uveal Melanoma Liver Metastases: A Multicenter, Randomized, Open-Label, Phase III Trial (the SCANDIUM Trial)
- 2023
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 41:16, s. 3042-50
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEAbout half of patients with metastatic uveal melanoma present with isolated liver metastasis, in whom the median survival is 6-12 months. The few systemic treatment options available only moderately prolong survival. Isolated hepatic perfusion (IHP) with melphalan is a regional treatment option, but prospective efficacy and safety data are lacking.METHODSIn this multicenter, randomized, open-label, phase III trial, patients with previously untreated isolated liver metastases from uveal melanoma were randomly assigned to receive a one-time treatment with IHP with melphalan or best alternative care (control group). The primary end point was overall survival at 24 months. Here, we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS), and safety.RESULTSNinety-three patients were randomly assigned, and 87 patients were assigned to either IHP (n = 43) or a control group receiving the investigator's choice of treatment (n = 44). In the control group, 49% received chemotherapy, 39% immune checkpoint inhibitors, and 9% locoregional treatment other than IHP. In an intention-to-treat analysis, the overall response rates (ORRs) were 40% versus 4.5% in the IHP and control groups, respectively (P < .0001). The median PFS was 7.4 months versus 3.3 months (P < .0001), with a hazard ratio of 0.21 (95% CI, 0.12 to 0.36), and the median hPFS was 9.1 months versus 3.3 months (P < .0001), both favoring the IHP arm. There were 11 treatment-related serious adverse events in the IHP group compared with seven in the control group. There was one treatment-related death in the IHP group.CONCLUSIONIHP treatment resulted in superior ORR, hPFS, and PFS compared with best alternative care in previously untreated patients with isolated liver metastases from primary uveal melanoma.
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| 14. |
- Olofsson, Roger, 1978, et al.
(författare)
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Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
- 2014
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15, s. 317-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
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| 15. |
- Olofsson, Roger, 1978, et al.
(författare)
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Isolated Hepatic Perfusion for Ocular Melanoma Metastasis: Registry Data Suggests a Survival Benefit.
- 2014
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Ingår i: Annals of surgical oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 21:2, s. 466-472
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Tidskriftsartikel (refereegranskat)abstract
- Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 35% of the patients, with the liver being the most common site for metastases. These metastases are generally refractory to systemic chemotherapy, and the median survival for patients with liver metastases is about 6months. This phase II trial reports the experience of isolated hepatic perfusion (IHP) as a treatment option.
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| 16. |
- Rizell, Magnus, 1963, et al.
(författare)
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Effects of the mTOR inhibitor sirolimus in patients with hepatocellular and cholangiocellular cancer.
- 2008
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Ingår i: International journal of clinical oncology / Japan Society of Clinical Oncology. - : Springer Science and Business Media LLC. - 1341-9625. ; 13:1, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hepatocellular cancer (HCC), as well as cholangiocellular cancer (CCC), has an extremely poor prognosis due to the extent of tumor at diagnosis and the underlying liver disease. Sirolimus is used in the transplantation setting as an immunosuppressive agent, but it also possesses antiproliferative and antiangiogenic properties. The objective of the study was to evaluate the effect of sirolimus on HCC and CCC. METHODS: In a prospective single-arm protocol, the tumor response to sirolimus as the primary endpoint was studied in 21 patients with advanced HCC and nine with CCC. Sirolimus was administered once daily by mouth, with the dose adjusted to a serum trough level between 4 and 15 mug/ml. Tumor response was evaluated by computed tomography (CT) or magnetic resonance imaging (MRI), according to the Response Evaluation Criteria in Solid Tumors (RECIST), every third month. Secondary measures were overall survival, time to tumor progression, tumor markers, and side effects. RESULTS: Of the patients with HCC, one had partial remission (PR) and fi ve patients had stable disease (SD) at 3 months. Of the patients with CCC, three had SD. The median survival for patients with HCC was 6.5 months (range, 0.2-36 months) and that for patients with CCC was 7 months (range, 2.6-35 months). CONCLUSION: Treatment of HCC and CCC with sirolimus can induce temporary PD or SD. This pilot study indicates that sirolimus might be a promising drug for this treatment, but further clinical studies elucidating the biological effects are advocated.
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| 17. |
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| 18. |
- Rizell, Magnus, 1963, et al.
(författare)
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Isolated hepatic perfusion for liver metastases of malignant melanoma.
- 2008
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Ingår i: Melanoma research. - 0960-8931. ; 18:2, s. 120-6
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to analyze the outcome of three treatment strategies using isolated hyperthermic liver perfusion (IHP) with melphalan for liver metastases of malignant melanoma. It was designed as an exploratory study. The setting was a single-center study in a university hospital. The study was carried out on 27 patients. IHP was used with modifications during three different time periods (IHP I, IHP II and IHP III), in technique and temperature (amount of melphalan: 0.5, 1.0 and 2 mg/kg body weight in the perfusate; 41, 40 and 40 degrees C). Tumor response was estimated according to WHO criteria with computed tomography or MRI. Mortality and morbidity were secondary measures. Six of 11 patients in the IHP I cohort experienced a partial response (PR). In the IHP II cohort, two patients of 11 experienced a complete response and five a PR. In the IHP III cohort, five of five patients experienced a PR. Six postoperative deaths were reported (27%) (three in the IHP I and three in the IHP II series), secondary to liver insufficiency and multiorgan failure. Treatment of liver metastases of malignant melanoma with isolated hyperthermic melphalan perfusion has shown an impressive tumor response rate, which seems to be higher than the response rates reported for other systemic chemotherapy regimens. The maximum tolerated dose for melphalan in the perfusate was surpassed with a 2 mg/kg body weight. By modifying the technique and restricting the allowed tumor burden, the response rate remained high and the mortality was reduced.
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| 19. |
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| 20. |
- Sternby Eilard, Malin, 1974, et al.
(författare)
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A prospective clinical trial on sorafenib treatment of hepatocellular carcinoma before liver transplantation
- 2019
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with hepatocellular carcinoma waiting for liver transplantation are commonly treated with locoregional treatments, such as TACE and ablation, to prevent tumor progression and dropout and to improve long-term outcome after transplantation. We wanted to prospectively assess feasibility of systemic antitumor treatment with sorafenib as neoadjuvant treatment for hepatocellular carcinoma while waiting for liver transplantation, evaluating tolerability, toxicity and posttransplant morbidity. We also wanted to evaluate perfusion CT parameters to assess tumor properties and response early after start of sorafenib treatment in patients with early hepatocellular carcinoma.MethodsTwelve patients assigned for liver transplantation due to hepatocellular carcinoma, within the UCSF and who fulfilled other criteria, were included January 2012-August 2014. After baseline evaluation, sorafenib treatment was started. Treatment was evaluated by perfusion CT at 1, 4 and 12weeks and thereafter every 8weeks. Toxicity and quality of life was assessed at 1 and 4weeks and every 4weeks thereafter during treatment. Treatment was stopped when patients were prioritized on the transplantation waiting list or when intolerable side effects or tumor progress warranted other treatments. Posttransplant morbidity after 90days was registered according to Clavien-Dindo.ResultsBaseline perfusion CT parameters in the tumors predicted the outcome according to RECIST/mRECIST at three months, but no change in CTp parameters was detected as a result of sorafenib. Sorafenib as neoadjuvant treatment was associated with intolerability and dose reductions. Therefore the prerequisites for evaluation of the sorafenib effect on both CT parameters and tumor response were impaired.ConclusionsThis study failed to show changes in CTp parameters during sorafenib treatment. Despite the curative treatment intention, tolerability of neoadjuvant sorafenib treatment before liver transplantation was inadequate in this study.Trial registrationEudraCT number: 2010-024306-36 (date 2011-04-07).
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| 21. |
- Sternby Eilard, Malin, et al.
(författare)
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Surgical treatment for gallbladder cancer - a systematic literature review
- 2017
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Ingår i: Scandinavian Journal of Gastroenterology. - : TAYLOR & FRANCIS LTD. - 0036-5521 .- 1502-7708. ; 52:5, s. 505-514
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Forskningsöversikt (refereegranskat)abstract
- Objective: To evaluate existing evidence regarding surgical treatments for gallbladder cancer in a Health Technology Assessment. A specific aim was to evaluate whether extended surgery regarding liver, lymph nodes, bile duct, and adjacent organs compared with cholecystectomy alone in the adult patient with gallbladder cancer in early and late stages implies improved survival. Methods: In April 2015 and updated in June 2016, a systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Two authors independently screened titles, abstracts, and full-text articles. The certainty of evidence was evaluated according to GRADE. Main results: Forty-four observational studies (non-randomised, controlled studies) and seven case series were included. Radical resection, including liver and lymph node resection, compared with cholecystectomy alone showed significantly better survival for patients with stages T1b and above. All studies had serious study limitations and the certainty of evidence was very low (GRADE circle plus(ooo)). A survival benefit seen in patients with stage T1b or higher with lymph node resection, was most evident in stage T2, but the certainty of evidence was low (GRADE circle plus circle plus(oo)). It is uncertain whether routine bile duct resections improve overall survival in patients with gallbladder cancer stage T2-T4 (GRADE circle plus(ooo)). Conclusion: Data indicate that prognosis can be improved if liver resection and lymph node resection is performed in patients with tumour stage T1b or higher. There is no evidence supporting resection of the bile duct or adjacent organs if it is not necessary in order to achieve radicality.
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| 22. |
- Söderdahl, G., et al.
(författare)
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A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma
- 2006
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Ingår i: Transplant international. - : Frontiers Media SA. - 0934-0874. ; 19:4, s. 288-94
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Tidskriftsartikel (refereegranskat)abstract
- The role of adjuvant systemic chemotherapy in liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial. Here, we report the results of a Nordic prospective, randomized, multi-centre trial of systemic low-dose doxorubicin in patients with HCC. Between February 1996 and April 2004, 46 patients were randomized to receive either neoadjuvant doxorubicin in combination with LT (chemo group; n = 19) or LT alone (control group; n = 27). In the chemo group, doxorubicin was administered intravenously, 10 mg/m(2) weekly, starting from acceptance onto the waiting list for LT. One intraoperative dose of 15 mg/m(2) was given, and postoperatively doxorubicin was given weekly at a dose of 10 mg/m(2), depending on the clinical course, up to a cumulative dose of 400 mg/m(2). Actuarial, 3-year overall survival (OS) and disease-free survival (DFS) in the control group were 70% and 50%, respectively. In the chemo group, both OS and DFS were 63%. Freedom from recurrence at 3 years was 55% in the control group and 74% in the chemo group. None of the differences was statistically significant. Neoadjuvant treatment with systemic low-dose doxorubicin seems not to improve either survival or freedom from recurrence in patients with HCC undergoing LT.
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