| 21. |
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| 22. |
- Hansson, Johan, 1964-, et al.
(författare)
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Single-photon emission computed tomography for prediction of treatment results in sequential intraperitoneal chemotherapy at peritoneal carcinomatosis
- 2012
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Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytoreductive surgery and intraperitoneal chemotherapy (IPC) treatment can improve survival in peritoneal carcinomatosis. One of the reasons for failure of sequential postoperative intraperitoneal chemotherapy (SPIC) is lack of distribution of the chemotherapy in the peritoneal cavity. The primary aim of this study was to evaluate single-photon emission computed tomography (SPECT) as a predictor of successful SPIC treatment and prognosis. A secondary aim was to assess the relationship between SPECT, feasibility of SPIC, and clinical variables.Methods: Fifty-one patients (mean age 52 years, range 14-74, 20 women) were treated with Cytoreductive surgery and SPIC. SPECT studies with intraperitoneal (i.p.) Technetium-99 via a Port-a-Cath (PaC) were performed before the second course of treatment. The i.p. distribution was registered as a detected volume (DV) at four different threshold settings (1, 2, 5, and 10%) of the global maximum intensity of the SPECT examination. A calculation model for SPECT and clinical variables was tested.Results: The DV measured in the SPECT examination predicted the number of subsequent SPIC courses. The highest correlation (R=0.45) for DV was in the 2% threshold setting. Patients with a DV2% lower than mean reached two SPIC courses and patients with a DV2% higher than mean reached six SPIC course. Height correlated to higher DV and a higher number of SPIC courses. Patients with a height lower than mean reached a DV2% at 3930 ml and patients higher than mean reached a DV2% at 5507 ml. A taller person could tolerate more SPIC courses (R=0.28) and patients with a height higher than mean reached six SPIC courses; patients with a height lower than mean reached four courses. There was no correlation between DV and survival.Conclusion: The feasibility of performing SPIC without further surgical intervention can be predicted by SPECT, and it might therefore be an instrument to select which patients should preferably be treated with alternative therapy.
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| 23. |
- 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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| 24. |
- Hultman, Bo, 1964-, et al.
(författare)
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Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy
- 2014
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Ingår i: Journal of Experimental & Clinical Cancer Research. - : Springer Science and Business Media LLC. - 1756-9966. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Background The choice of drugs for treatment of advanced gastric cancer (GC) is empirical. The purpose of the current study was to benchmark ex vivo the sensitivity of GC tumor cells from patients to standard cytotoxic and some newly introduced targeted drugs (TDs), as a basis for drug selection in the treatment of GC.Methods Tumor cell samples from patients with GC were analyzed for sensitivity to 5-fluorouracil, cisplatin, oxaliplatin, irinotecan, mitomycin C, doxorubicin and docetaxel as well as for the targeted drugs bortezomib, sorafenib, sunitinib and rapamycin using a short-term in vitro assay based on retention of viable tumor cells of fluorescent fluorescein. Samples of normal mononuclear cells, chronic lymphocytic leukemia, ovarian cancer and colorectal cancer were included for comparison.Results The GC samples were essentially as sensitive to the standard drugs and the TDs as those from colorectal cancer whereas the ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the clinically used standard drugs. In GC, cisplatin was cross-resistant to oxaliplatin and 5-fluorouracil which, on the other hand, was not cross-resistant to the other cytotoxic drugs. The activity of sunitinib did not obviously correlate to that of the standard drugs.Conclusion Ex vivo assessment of drug sensitivity of tumor cells from patients with GC is feasible and may provide information that could be useful for selection of drugs for treatment. Drug sensitivity varies considerably between and within individual samples arguing for individualized selection of drugs for chemotherapy.
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| 25. |
- Hultman, Bo, 1964-
(författare)
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Clinical and Experimental Studies in Peritoneal Metastases from Gastric Cancer
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gastric cancer (GC) is one of leading causes of death in the world, and peritoneal metastases (PM) are a major site of recurrence. PM from GC implies a poor prognosis, with median overall survival (mOS) approximately 3 months and no survival at five years.The aims of this thesis were to explore the incidence and evaluate prognostic factors for mOS of PM from GC in a defined population; to investigate the outcome of a new multimodal treatment; to analyse the treatment costs, and to investigate differences in drug sensitivity between individual patient samples and between various tumours.The incidence of loco-regional advanced GC was 3.8 per 100,000 person-years. Synchronous loco-regional GC in combination with synchronous distant metastasis was a negative prognostic factor while chemotherapy and good performance status, and radiotherapy plus chemotherapy were positive prognostic factors . There were no significant differences in mOS for the group of patients included during the period 2000-2004 versus 2005-2009, and this lack of improvement in mOS during the past decade justifies new treatment approaches.In a Phase II study of patients treated with neoadjuvant systemic chemotherapy followed by cytoreductive surgery + hyperthermic intraperitoneal chemotherapy, mOS was 14.3 months and for patients with macroscopically radical surgery mOS was 19.1 months. The mean overall cost of the loco-regional treatment was $145,700 compared to $59,300 with systemic chemotherapy treatment.In an ex vivo chemo-sensitivity test, it was determined that GC samples were equivalent to colorectal cancer in chemo-sensitivity to standard drugs and targeted drugs, whereas ovarian cancer samples were more sensitive. The individual GC samples varied considerably in sensitivity to increasing concentrations of the drugs, arguing for individualized drug selection. The incidence of loco-regional advanced GC was more common than previously reported and there were no improvements in mOS over the past decade. The mOS for patients with neoadjuvant systemic chemotherapy followed by macroscopically radical cytoreductive surgery + hyperthermic intraperitoneal chemotherapy was better than in recent reports on treatment with systemic chemotherapy. Treatment of advanced GC patients is costly irrespective of treatment modality. The GC samples varied considerably between individuals in terms of sensitivity to increasing concentrations of the drugs and were comparable to colorectal cancer in chemo-sensitivity.
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| 26. |
- Hultman, Bo, et al.
(författare)
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Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer
- 2012
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 112-121
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe costs for loco-regional treatment of peritoneal carcinomatosis from gastric cancer are not well investigated. The aims of this study were to evaluate the costs and clinical outcome of systemic chemotherapy followed by cytoreductive surgery and intraperitoneal chemotherapy compared to systemic chemotherapy only in patients with peritoneal carcinomatosis from gastric cancer.Material and methodsTen patients were scheduled for systemic chemotherapy followed by loco-regional treatment. A reference group of 10 matched control patients treated with systemic chemotherapy only were used and both groups were evaluated with respect to clinical outcome and cost.ResultsThe mean overall cost in the loco-regional group was $145 700 (range $49 900-$487 800) and $59 300 (range $23 000-$94 800) for the control group. The mean overall survival for the loco-regional group was 17.4 months (range 6.0-34.3), and 11.1 months (range 0.1-24.2) for the systemic chemotherapy only group. The gain in life-years was 0.52 and in quality-adjusted life-years 0.49, leading to incremental cost per life-year and quality-adjusted life-years gained of $166 716 and $175 164, for loco-regional group compared to systemic chemotherapy.DiscussionTreatment of peritoneal carcinomatosis from gastric cancer is costly irrespective of treatment modality. If the survival benefit from adding loco-regional treatment to systemic chemotherapy indicated from this comparison is true, the incremental cost is considered high.
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| 27. |
- Hultman, Bo, et al.
(författare)
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Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
- 2013
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:4, s. 824-830
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim was to evaluate the feasibility and the effectiveness of neoadjuvant systemic chemotherapy followed by cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) in patients with peritoneal carcinomatosis (PC) from gastric cancer.Material and methodsEighteen patients (median age 57 years, range 38-74) were scheduled for three months' neoadjuvant systemic chemotherapy followed by CRS + HIPEC + EPIC.ResultsAt the time of surgery, the peritoneal tumor burden was extensive with tumor growth on the entire peritoneal cavity. Only eight patients received the entire treatment and OS was 14.3 months (range 6.1-34.3, 95% CI 6.6-20.3). Six patients had macroscopically radical (CC0) surgery and for this subgroup OS was 19.1 months (range 6.1-34.3, 95% CI 6.9-27.1). Postoperative 90-day mortality was 10% (one patient) and the perioperative grades II-IV adverse events (AE) rate was 62.5%.DiscussionNeoadjuvant chemotherapy followed by CRS + HIPEC + EPIC does not seem to be associated with prolonged OS in patients with extensive PC growth from gastric cancer unless macroscopically radical surgery is achieved. However, morbidity from this treatment is considerable and it cannot be recommended for routine care until a prospective randomized trial has been performed.
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| 28. |
- Krause, Johan, et al.
(författare)
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Ultrasonography findings and tumour quantification in patients with pseudomyxoma peritonei
- 2012
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Ingår i: European Journal of Radiology. - : Elsevier BV. - 0720-048X .- 1872-7727. ; 81:4, s. 648-651
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Tidskriftsartikel (refereegranskat)abstract
- Pseudomyxoma peritonei (PMP) is a disease with various clinical presentations and the diagnostic value of ultrasonography (US) is under investigated. The purpose of this study was to identify the most common US finding in PMP and to investigate US sensitivity, specificity, positive and negative predictive value in quantifying tumour burden in different abdomino-pelvic regions in PMP patients. Between February 2006 and December 2008, 54 patients were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) due to PMP. The results from preoperative US examination with and without intravenously administrated contrast (SonoVue) were compared to surgical findings. The mean US peritoneal cancer index (PCI) was 6 (range 0-25) and the surgical PCI was 18 (range 3-27) p<0.0001. The histo-pathological subtypes did not influence the US findings. Ascites, bowel loops adhesions and omental cake were mostly visualised correctly by US. The sensitivity of US in quantification of tumour nodules was 91.5% (range 74-100%) and specificity was 33.8% (range 18-55%). The positive predictive value of US examination in PMP was 22% (range 11-44%) and the negative predictive value was 93% (range 77-100%). US can detect the most common PMP findings (ascites and omental cake). The sensitivity of US to quantify PMP tumour burden in different abdominio-pelvic region was relatively high, however, this imaging tool had low specificity.
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| 29. |
- Lorant, Tomas, et al.
(författare)
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Sinus Excision and Primary Closure Versus Laying Open in Pilonidal Disease : A Prospective Randomized Trial
- 2011
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Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 54:3, s. 300-305
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgical excision is the standard treatment for chronic pilonidal disease, but all excisional techniques are associated with tissue loss, risk of wound break down, and chronic healing problems. OBJECTIVE: The aim of the study was to compare sinus excision and primary closure vs a laying open technique in a prospective randomized trial. DESIGN, PATIENTS, AND INTERVENTIONS: Eighty patients were randomly assigned to sinus excision and primary closure (n = 39) or laying open (n = 41). Follow-up was performed 1, 3, and 12 months after surgery. MAIN OUTCOME MEASURE: The main outcome measure was the healing rate after 1 year. RESULTS: The healing rate was significantly higher after excision and closure than after laying open at 1 month (20 of 39 vs 8 of 41; P=.005) and 3 months (36 of 38 vs 28 of 39; P=.013) after surgery. At follow-up 12 months after surgery no difference was seen in healing rate between the treatment arms (33 of 37 vs 37 of 38; P=.198). CONCLUSIONS: This prospective randomized trial shows that sinus excision and primary closure results in faster healing than laying open does, but there is no difference in healing rate after 1 year. The laying open procedure is minimally invasive with small risks for the patient, and it might therefore be considered more frequently as the first choice of treatment (www.clinicaltrials.gov. Unique identifier: NCT00997048).
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| 30. |
- Näslund Andréasson, Sara, et al.
(författare)
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Is Platinum Present in Blood and Urine from Treatment Givers during Hyperthermic Intraperitoneal Chemotherapy?
- 2010
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Ingår i: Journal of oncology. - : Hindawi Limited. - 1687-8469 .- 1687-8450. ; 2010, s. 649719-
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Tidskriftsartikel (refereegranskat)abstract
- Background. In selected patients with peritoneal carcinomatosis (PC) originating from colorectal cancer (CRC) the high dosage of oxaliplatin (460 mg/m(2)) is recommended for hyperthermic intraperitoneal chemotherapy (HIPEC), which may be a health risk to those administering the drug. The aim of this study was to determine the risk of platinum (Pt) exposure for the two main people handling and administering the cytotoxic agent during HIPEC. Methods. Samples of blood and urine were collected from one male surgeon and one female perfusionist during oxaliplatin-based HIPEC treatment with open abdomen coliseum technique on six consecutive patients with PC from CRC. Results. All blood samples analysed were below the detection limit of <0.05 nmol/L Pt, and the urine samples were all below the detection limit of <0.03 nmol/L Pt. Conclusions. There appears to be little or no risk of Pt exposure during HIPEC when the recommended protective garment is used and the safety considerations are followed.
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