| 1. |
- Andreasson, Håkan, et al.
(författare)
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Histopathological classification of pseudomyxoma peritonei and the prognostic importance of PINCH protein
- 2012
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 32:4, s. 1443-1448
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.MATERIALS AND METHODS: Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.RESULTS: The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).CONCLUSION: The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.
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| 2. |
- Andréasson, Håkan, et al.
(författare)
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Outcome differences between debulking surgery and cytoreductive surgery in patients with pseudomyxoma peritonei
- 2012
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 38:10, s. 962-968
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The aim of this study was to compare debulking surgery and cytoreductive surgery (CRS) in patients with Pseudomyxoma peritonei (PMP) regarding efficacy and safety.PATIENTS AND METHODS:Data were extracted from medical records and treatment outcomes were analyzed for all 152 patients with PMP who were scheduled for debulking surgery and intraperitoneal chemotherapy (IPC) or CRS and IPC at Uppsala University Hospital, Uppsala, Sweden, between September 1993 and December 2008.RESULTS:One hundred and ten patients (73%) were treated with CRS and IPC and 40 (27%) with debulking surgery and IPC. In two patients (1%), surgery was defined as open and close. Patients with CRS and IPC had a 74% 5-year overall survival (OS) rate compared with 40% for those treated with debulking surgery (P < 0.001). Patients with no residual macroscopic tumour (R1 resection) had a better 5-year OS rate of 94% compared with 28% for patients with macroscopic residual tumour (R2) (P < 0.001). Grades II-IV adverse events were seen in 29% of debulked patients and in 47% of CRS/IPC patients (P = 0.053).CONCLUSIONS:CRS and IPC seems more efficient than debulking surgery and IPC but with numerically higher morbidity. Therefore, if surgically possible, CRS should be the treatment of choice for PMP patients. However, debulking surgery may still be of benefit to selected patients for palliative purposes.
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| 3. |
- Cashin, Peter H., et al.
(författare)
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Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases : A randomised trial
- 2016
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 53, s. 155-162
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Tidskriftsartikel (refereegranskat)abstract
- Background: First-line treatment of isolated resectable colorectal peritoneal metastases remains unclear. This study (the Swedish peritoneal study) compares cytoreductive surgery and intraperitoneal chemotherapy (surgery arm) with systemic chemotherapy (chemotherapy arm). Methods: Patients deemed resectable preoperatively were randomised to surgery and intraperitoneal 5-fluorouracil 550 mg/m(2) /d for 6 d with repeated courses every month or to systemic oxaliplatin and 5-fluorouracil regimen every second week. Both treatments continued for 6 months. Primary end-point was overall survival (OS) and secondary end-points were progression-free survival (PFS), and morbidity. Results: The study terminated prematurely when 48 eligible patients (24/arm) were included due to recruitment difficulties. Two-year OS was 54% in the surgery arm and 38% in the chemotherapy arm (p = 0.04). After 5 years, 8 versus 1 patient were alive, respectively (p = 0.02). Median OS was 25 months versus 18 months, respectively, hazard ratio 0.51 (95% confidence interval: 0.27-0.96, p = 0.04). PFS in the surgery arm was 12 months versus 11 months in the chemotherapy arm (p = 0.16) with 17% versus 0% 5-year PFS. Grade III-IV morbidity was seen in 42% and 50% of the patients, respectively. No mortalities. Conclusions: Cytoreductive surgery with intraperitoneal chemotherapy may be superior to systemic oxaliplatin-based treatment of colorectal cancer with resectable isolated peritoneal metastases.(ClinicalTrials. gov nr: NCT01524094).
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| 4. |
- Cashin, Peter, 1984-, et al.
(författare)
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Quality of life and cost effectiveness in a randomized trial of patients with colorectal cancer and peritoneal metastases
- 2018
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Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 44:7, s. 983-990
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to compare health-related quality-of-life (HRQOL) and cost-effectiveness between cytoreductive surgery with intraperitoneal chemotherapy (CRS + IPC) and systemic chemotherapy for patients with colorectal peritoneal metastases. Methods: Patients included in the Swedish Peritoneal Trial comparing CRS + IPC and systemic chemotherapy completed the EORTC QLQ-C30 and SF-36 questionnaires at baseline, 2, 4, 6, 12, 18, and 24 months. HRQOL at 24 months was the primary endpoint. EORTC sum score, SF-36 physical and mental component scores at 24 months were calculated and compared for each arm and then referenced against general population values. Two quality-adjusted life-year (QALY) indices were applied (EORTC-8D and SF-6D) and an incremental cost-effectiveness ratio (ICER) per QALY gained was calculated. A projected life-time ICER per QALY gained was calculated using predicted survival according to Swedish population statistics. Results: No statistical differences in HRQOL between the arms were noted at 24 months. Descriptively, survivors in the surgery arm had higher summary scores than the general population at 24 months, whereas survivors in the chemotherapy arm had lower scores. The projected life-time QALY benefit was 3.8 QALYs in favor of the surgery arm (p=0.06) with an ICER per QALY gained at 310,000 SEK (EORTC-8D) or 362,000 SEK (SF-6D) corresponding to 26,700-31,200 GBP. Conclusion: The HRQOL in patients with colorectal peritoneal metastases undergoing CRS + IPC appear similar to those receiving systemic chemotherapy. Two-year survivors in the CRS + IPC arm have comparable HRQOL to a general population reference. The treatment is cost-effective according to NICE guidelines.
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| 5. |
- Graf, Wilhelm, et al.
(författare)
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Induction and quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 608-614
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Tidskriftsartikel (refereegranskat)abstract
- Nude rats were injected with human colonic cancer cells (LS 174 T) in the superior mesenteric vein and the extent of hepatic metastases at sacrifice was estimated by visual inspection and computer-based area calculation. After 3 weeks, 5.0 x 10(6) cells caused hepatic metastases in 14/14 rats whereas 0.5 x 10(6) cells failed to produce liver metastases in 4/4 rats (P < 0.001). Injection of 1.0 x 10(7) cells caused portal vein occlusion in 3/5 rats. Extrahepatic tumour growth was rare; lung metastases were observed in four rats, and three rats had local tumour in the abdomen. The average extent of hepatic tumour replacement was 20.2 +/- 4.0%. Injection of embolies or single cells did not affect the incidence or extent of hepatic metastases. The incidence of hepatic metastases was similar in male and female rats, but the extent of hepatic tumour was larger in males (24.6%) than in females (3.2%) (P = 0.005). The pathophysiological similarities to human disease should make this model suitable for diagnostic and therapeutic studies with clinical application.
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| 6. |
- Hansson, Johan, 1964-, et al.
(författare)
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Quality of life in peritoneal carcinomatosis after cytoreductive surgery and intraperitoneal chemotherapy
- 2012
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Tidskriftsartikel (refereegranskat)abstract
- Background:Cytoreductive surgery (CRS) plus intraperitoneal chemotherapy (IPC) is considered the most optimal treatment for peritoneal carcinomatosis (PC). Health-related quality of life (HRQL) after treatment is largely unknown. The aims were to assess HRQL in patients with PC treated with CRS and IPC and to analyse the influence of clinical variables on HRQL.Methods:HRQL was assessed prospectively between November 2001 and March 2005 in 64 consecutive patients with PC through two different self-administered instruments, EORTC QLQ-C30 v3.0 (QLQ-C30) and the SF-36 Health Survey (SF-36), preoperatively, and after 3 and 8 months. Results:For QLQ-C30, 44 (69%) and for SF-36, 42 (66%) out of 64 patients had a complete follow-up. Most scales were worsened at baseline compared to reference in both instruments. HRQL was reduced at 3-months in QLQ-C30 (physical, role and emotional functioning) and in SF-36 (physical summary score). At 8-months, all scales returned to baseline in QLQ-C30, except physical functioning which was still reduced and dyspnoea that was worsened. In SF-36, all values returned to baseline levels. At 8-months, presence of a stoma worsened social functioning and a high peritoneal cancer index decreased social functioning and global QoL, the use of hyperthermic intraperitoneal chemotherapy and 30-days postoperative morbidity had no impact on HRQL. Conclusion: CRS with IPC results in reasonable short-term HRQL despite high initial morbidity and an initial decrease in HRQL parameters. The study adds to the notion that this treatment appears beneficial in light of probable life prolongation, despite considerable toxicity.
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| 7. |
- Hassan, Saadia, et al.
(författare)
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Novel activity of acriflavine against colorectal cancer tumor cells
- 2011
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 102:12, s. 2206-2213
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Tidskriftsartikel (refereegranskat)abstract
- A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.
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| 8. |
- Mahteme, Haile, et al.
(författare)
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Heterogeneous activity of cytotoxic drugs in patient samples of peritoneal carcinomatosis
- 2008
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 34:5, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To investigate if the pattern of cytotoxic drug sensitivity in vitro in patient samples of peritoneal carcinomatosis (PC) is supportive to the current standardized approach for drug selection for perioperative intraperitoneal chemotherapy (IPC). METHODS: The cytotoxic effect of cisplatin, oxaliplatin, irinotecan, 5-fluorouracil, mitomycin-C, doxorubicin and melphalan was investigated in vitro on tumour cells from 223 patient tumour samples of different PC origins. RESULTS: Considerable differences in cytotoxic drug sensitivity between tumour types of the PC entity and within each tumour type were observed. Cisplatin showed high cross-resistance with oxaliplatin but low cross-resistance with doxorubicin and irinotecan. No cross-resistance was found between irinotecan and doxorubicin. The dose-response relationships for melphalan and irinotecan in individual samples showed great variability. CONCLUSIONS: The activity in vitro of cytotoxic drugs commonly used in IPC for PC is very heterogeneous. Efforts for individualizing drug selection for PC patients undergoing IPC seem justified.
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| 9. |
- Sundín, Anders, et al.
(författare)
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Contrast-enhanced CT scanning in vivo for the quantification of hepatic metastases from a human colonic cancer in the nude rat
- 1992
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Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 18:6, s. 615-623
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic metastases were induced in nude rats by intraportal injection of 2.5-5.0 x 10(6) cells from the human colonic cancer cell line LS 174 T. Quantification of tumour burden, expressed as relative metastatic area, was performed by contrast-enhanced computed tomography (CT) scanning in vivo (n = 14), contrast enhanced CT scanning post mortem (n = 21) and computer-based area calculation (CBAC) (n = 21). To determine the false-positive contribution to the estimated tumour burden by the evaluation procedures themselves, six rats without metastases were assessed. The quantification in the three different assessment groups was in close accordance in animals with an intermediate or extensive metastatic burden, but not in rats with a minor (< 4%) tumour burden. The results indicate that contrast-enhanced CT scanning can be used in this model to quantify hepatic metastases, except in animals with few and small lesions. Furthermore, the results suggest a potential for the assessment of therapeutic response by repeated contrast-enhanced CT scanning in vivo, as well as prospects for a corresponding evaluation in man.
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| 10. |
- Sundín, Anders, et al.
(författare)
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Radioimmunolocalization of hepatic metastases and subcutaneous xenografts from a human colonic cancer in the nude rat : Aspects of tumour implantation site and mode of antibody administration
- 1993
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 32:7-8, s. 877-885
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Tidskriftsartikel (refereegranskat)abstract
- Antibody localization was analyzed following intraperitoneal (i.p.) or intravenous (i.v.) injection of the 125I-labelled anti-CEA-MAb I-38S1 in 44 nude rats, in order to evaluate the influence of tumour implantation site and the route of MAb administration. The animals were xenografted with a human colonic cancer (LS 174 T), either in the form of hepatic metastases, subcutaneous (s.c.) tumours or both. Tissue measurements, 4 days after MAb injection, showed better uptake for hepatic than for s.c. tumours, irrespective of the route of antibody administration. Antibody accumulation per g liver metastases was not size dependent for noduli weighing between 4 and 1,110 mg. MAb excretion evaluated in 20 animals and blood activity studied in 11 rats were equivalent 24-96 h following i.p. and i.v. injection. Dissimilar autoradiographic patterns were seen in hepatic metastases with predominantly peripherally located clusters following i.p. and more homogeneously distributed grains after i.v. MAb administration. The results indicate that tumour implantation site has a quantitative, and the route of administration at least a qualitative impact on the tumour accretion of anti-CEA MAb I-38S1 in the present xenograft model.
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