| 1. |
- Andréasson, Sara Näslund, et al.
(författare)
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Peritonectomy with high voltage electrocautery generates higher levels of ultrafine smoke particles
- 2008
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 35:7, s. 780-784
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To adequately perform peritonectomy, the use of an electrocautery device at a high voltage is recommended. The aim of this study was to analyse the amount of airborne and ultrafine particles (UFP) generated during peritonectomy and to compare this with standard colon and rectal cancer surgery (CRC). METHOD: UFP was measured approximately 2-3cm from the breathing area of the surgeon (personal sampling) and 3m from where the electrocautery smoke was generated (stationary sampling) from 14 consecutive peritonectomy procedures and 11 standard CRC resections. The sampling was by P-Trak UFP counter that has the capacity to detect particle size ranging from 0.02 to 1mum. RESULTS: The cumulative level of UFP of personal sampling in the peritonectomy group was higher (9.3x10(6)particle/ml/h (pt/ml/h)) than in the control group (4.8x10(5)pt/ml/h). A higher cumulative level of UFP in stationary sampling was observed in the PC group (2.6x10(6) pt/ml/h) than in the control group (3.9x10(4)pt/ml/h). CONCLUSION: Peritonectomy procedure with high voltage electrocautery generates elevated levels of UFP than standard CRC surgery does. The level of UFP produced by a peritonectomy is comparable to cigarette smoking. More efficient smoke evacuator systems are needed in order to reduce the levels of UFP generated during electrocautery surgery.
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| 2. |
- Ceelen, Wim P., et al.
(författare)
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Pharmacodynamic aspects of intraperitoneal cytotoxic therapy
- 2007
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Ingår i: Cancer treatment and research. - 0927-3042. ; 134, s. 195-214
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Tidskriftsartikel (refereegranskat)abstract
- The rationale for ip administration as an adjunct to surgery is firmly based on theoretical and pharmacokinetic grounds. The superiority of combined ip and intravenous chemotherapy over intravenous chemotherapy alone has been established in randomized trials in stage IIIc ovarian cancer patients. Intraoperative ip cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption. At present, however, it is not clearly established to what extent this PK advantage will result in enhanced anticancer activity and, ultimately, in a survival benefit. Preclinical models show that direct penetration into tumour tissue is limited to a few millimeters. Furthermore, the limited exposure time of intraoperative chemoperfusion could limit cytotoxic activity despite high local concentrations. Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia. Newer agents such as the taxanes and the camptothecins appear promising for ip chemoperfusion during or immediately after surgery. Pharmacodynamic aspects of HIPEC needing further preclinical study-including mathematical modeling - are the establishment of tumour tissue penetration of the newer agents and its relation to hyperthermia, the definition of the relative contribution of direct penetration versus vascular supply by absorbed drug, and the efficacy of combined ip and intravenous regimens. Ultimately, however, randomised trials of ip chemotherapy with surgery will have to provide the evidence base to further build upon.
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| 3. |
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| 4. |
- Hansson, Johan, 1964-
(författare)
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Loco-regional Treatment of Peritoneal Carcinomatosis: Survival, Morbidity and Quality of Life
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Peritoneal carcinomatosis (PC) is traditionally regarded as a terminal stage of disease with a poor prognosis and systemic chemotherapy is regarded as palliative treatment. In order to improve survival and even to achieve cure for selected patients with PC, cytoreductive surgery and intraperitoneal che-motherapy have been advocated. Despite complete macroscopic removal of tumour, residual microscopic malignant cells might result in recurrence. Intraperitoneal chemotherapy aims to kill residual malignant cells and thereby needs to be distributed in the entire peritoneal cavity. This aggres-sive combined loco-regional treatment has a high risk of morbidity and mor-tality. Whether the increased risks are acceptable to improve survival re-quires investigation and the impact of loco-regional treatment of PC on health-related quality of life (HRQL) needs to bee explored The overall aim of this thesis was to analyse the impact of cytoreductive surgery and intraperitoneal chemotherapy on patients with peritoneal carci-nomatosis. A significant survival improvement (median 32 months) was seen in 18 patients with PC of colorectal origin subjected to loco-regional treatment, in comparison to matched controls treated with systemic chemotherapy (me-dian survival 14 months, Paper I). The results of single-photon emission computer-tomography (SPECT) in 51 patients were correlated to the number of intraperitoneal chemotherapy courses that could be performed without further surgery (Paper II). Postoperative 30-days morbidity and 90-days mortality was investigated in 123 PC-patients after loco-regional treatment. Severe adverse events occurred in 51 (41%) patients. Five patients (4%) had treatment-related mortality. Stoma formation, duration of surgery, periopera-tive blood loss, and extent of PC was associated with morbidity (Paper III). HRQL was investigated in 64 patients. HRQL was negatively affected at 3 months but a partial recovery was seen at 8 months. 30-day morbidity did not have any impact on HRQL at 8 months (Paper IV). This treatment there fore appears justified despite considerable toxicity in view of possible life prolongation.
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| 5. |
- Hansson, Johan, et al.
(författare)
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Postoperative adverse events and long-term survival after cytoreductive surgery and intraperitoneal chemotherapy
- 2009
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Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 35:2, s. 202-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Peritoneal carcinomatosis (PC) is fatal without special combined cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). This study was designed to identify factors that may increase the risk of postoperative morbidity and mortality from combined CRS and IPC interventions for PC. Survival based on primary tumour type and extent of surgery is reported. METHODS: Between May 1991 and November 2004, 123 patients were treated with CRS and IPC for PC. Based on the National Cancer Institute Common Toxicity Criteria for grade 3 and 4, data on 30 days postoperative morbidity and 90 days mortality were analysed. RESULTS: Grade 3-4 adverse events were observed in 51 patients (41%) and were associated with stoma formation, duration of surgery, peroperative blood loss and peritoneal cancer index (PCI). Excision, or electrocautery evaporation, of tumour from small bowel surface was correlated to bowel morbidity. Five patients had treatment-related mortality (4%) within 90 days. Survival was associated with macroscopic radical surgery, prior surgical score, PCI and primary tumour type. CONCLUSIONS: CRS and IPC for PC are associated with high morbidity and mortality. However, in light of the potential benefit indicated by long-term survival, the adverse event from this treatment is considered acceptable.
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| 6. |
- Mahteme, Haile, et al.
(författare)
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5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction : an autoradiographic study in the rat
- 2005
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 25:2A, s. 917-922
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Tidskriftsartikel (refereegranskat)abstract
- This study was conducted to test if tumour drug uptake could be increased in experimental colorectal cancer peritoneal metastases, by using pretreatment with peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5-FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU, group I (control) received i.p. NaCl, group II was subjected to i.p. radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake was visualised with autoradiography and quantified by computer-based image analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than in group I (11.8+/-10, p=0.04). This was also true when the analysis was restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs. group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels), in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by pretreating the animals with Norbormide. These results demonstrate that 5-FU uptake in experimental peritoneal metastases is increased when the peritoneal absorption of the drug is blocked using pretreatment with a vasoconstrictive agent. This principle may also be relevant when treating patients with colorectal cancer peritoneal metastases.
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| 7. |
- Mahteme, Haile, et al.
(författare)
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Good colorectal cancer surgery.
- 2005
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Ingår i: Tech Coloproctol. - 1123-6337. ; 9:1, s. 1-7
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Tidskriftsartikel (refereegranskat)
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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. |
- Mahteme, Haile, et al.
(författare)
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Systemic exposure of the parent drug oxaliplatin during hyperthermic intraperitoneal perfusion
- 2008
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 64:9, s. 907-911
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the perfusate and systemic kinetics of oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) using a selective analytical technique. Methods HIPEC was carried out in eight patients by the open abdomen coliseum technique for 30 min at 41.5-43 degrees C with an average of 427 mg/m(2) of oxaliplatin in 5% dextrose solution. Blood and perfusate samples were collected during the perfusion. Additional blood samples were taken up to 2 h after the end of perfusion. The analysis was performed by liquid chromatography and post-column derivatization with N,N-diethyldithiocarbamate using microwave heating. Results The mean elimination half-life of oxaliplatin in the perfusate was 29.5 min (range 21.1-41.2 min) and in the peripheral circulation 24.7 min (range 21.7-27.7 min). The ratio of the areas under the time concentration curve in perfusate and blood was 12.8 +/- 2.9. Conclusion The systemic exposure of oxaliplatin measured after HIPEC using a selective analytical technique is considerably lower than previously reported results obtained by atomic absorption spectroscopy.
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| 10. |
- Van der Speeten, Kurt, et al.
(författare)
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A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin
- 2009
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Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer Science and Business Media LLC. - 0344-5704 .- 1432-0843. ; 63:5, s. 799-805
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A pharmacologic analysis of intracavitary doxorubicin in the treatment of patients with intracavitary cancer dissemination was performed to further evaluate the possible benefits of this treatment modality. METHODS: Twenty appendiceal malignancy patients with peritoneal carcinomatosis (PC), three appendiceal malignancy patients with direct extension into the pleural cavity, 20 patients with peritoneal mesothelioma and one patient with pleural mesothelioma were available for pharmacologic monitoring. After intraperitoneal or intrapleural administration of doxorubicin, plasma and peritoneal fluid samples were obtained at 15, 30, 45, 60 and 90 min in all patients. After intrapleural administration, plasma and pleural fluid samples were collected at similar intervals. Tumor and normal tissues were obtained when available. Doxorubicin concentrations were determined by high-performance liquid chromatography (HPLC). RESULTS: Intraperitoneal doxorubicin showed a prolonged retention in the peritoneal cavity. Doxorubicin concentrations in tumor tissue were consistently elevated above intraperitoneal concentrations from 30 through 90 min. For appendiceal malignancy, the concentrations of doxorubicin were significantly higher in minimally aggressive mucinous tumors. Pleural chemotherapy solutions retained doxorubicin to a greater extent than peritoneal fluid. CONCLUSIONS: Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.
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