Cashin P.,Section of Surgery |
Cashin P.,Uppsala University Hospital |
Nygren P.,Radiology and Clinical Immunology |
Hellman P.,Section of Surgery |
And 3 more authors.
Clinical Colorectal Cancer | Year: 2011
Purpose: The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (AAC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology. Methods: Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC. Results: Patients with completeness of cytoreduction score (CC) ≤ 1 had better median survival (36.6 months) than those with CC > 1 (16.4 months). In the CC ≤ 1 group, 8 months elapsed between initial diagnosis and CRS with HIPEC compared with 22 months in the CC ≤ 1 group. For standard drugs, tumor cells from AAC and CRC were equally sensitive; except for docetaxel, to which AAC was more sensitive than CRC. Conclusion: The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of AAC, although other drugs, eg, docetaxel, might be more active. © 2011 Elsevier Inc. All rights reserved.
Back J.,Radiology and Clinical Immunology |
Sanchez J.,Radiology and Clinical Immunology |
Elgue G.,Radiology and Clinical Immunology |
Ekdahl K.N.,Radiology and Clinical Immunology |
And 2 more authors.
Biochemical and Biophysical Research Communications | Year: 2010
Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation, in the presence of a negatively charge substance or material. Still proof is lacking that FXII is activated by platelets in a more physiological environment. In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood. Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thrombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed, demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation. Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected on activated platelets. Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated. Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time. We conclude that platelet activation triggers FXII-mediated contact activation on the surface and in the vicinity of activated platelets. This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation. Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation. © 2009.
Pettersson D.,Karolinska Institute |
Cederniark B.,Karolinska Institute |
Holm T.,Karolinska Institute |
Radu C.,Radiology and Clinical Immunology |
And 3 more authors.
British Journal of Surgery | Year: 2010
Background: To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. Methods: Some 303 patients were randomized to either short-course RT (5 × 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4-8 weeks (group 2) or long-course RT (25 × 2 Gy) and surgery after 4-8 weeks (group 3). Results: Demographic data were similar between groups and there were few protocol violations (5-0-6 per cent). Eight patients (2-6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46-6, 40-0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0.164). Patients receiving short-course RT with surgery 11-17 days after the start of RT had the highest complication rate (24 of 37). Conclusion: Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. Registration number: NCT00904813 (http://www.clinicaltrials.gov). Copyright © 2010 British Journal of Surgery Society Ltd.