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Sökning: WFRF:(Mahteme Haile)

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31.
  • Hansson, Johan, 1964-, et al. (författare)
  • Single-photon emission computed tomography for prediction of treatment results in sequential intraperitoneal chemotherapy at peritoneal carcinomatosis
  • 2012
  • Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140.
  • 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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32.
  • Hassan, Saadia, et al. (författare)
  • Novel activity of acriflavine against colorectal cancer tumor cells
  • 2011
  • Ingår i: Cancer Science. - 1347-9032 .- 1349-7006. ; 102:12, s. 2206-2213
  • 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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33.
  • Hultman, Bo, 1964-, et al. (författare)
  • A population-based study of incidence of peritoneal metastases and prognostic factors in patients with loco-regionally advanced gastric cancer
  • ????
  • Annan publikation (övrigt vetenskapligt)abstract
    • Purpose   The aim was to investigate epidemiological and prognostic factors as a knowledge base for the treatment of patients with loco-regionally advanced gastric cancer (GC). Methods   In Uppsala County between 2000 and 2009, two hundred and fifty-five patients with GC were identified. Data from patient records were analyzed for loco-regionally advanced GC, defined as tumor invading the parietal and/or visceral peritoneum, including peritoneal metastasis but excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. Presence or absence of distant metastasis (DM) in these patients was also assessed. Results   One hundred and twenty patients (47% of all patients with GC) experienced loco-regionally advanced disease. Forty-one percent also had DM. Median overall survival (mOS) from diagnosis of local-regionally advanced disease was 4.8 months for the whole group of patients, 5.1 months for the subgroup of patients without DM and 4.7 months for the subgroup with DM. Using multivariate Cox analysis, positive prognostic factors for survival identified were good performance status and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative predictive factor. The mOS did not differ between the first and second time period. Discussion   Peritoneal metastasis from GC is more common than previously reported. The lack of improvement in OS over the past decade signals a need for new treatment strategies.
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34.
  • Hultman, Bo, 1964-, et al. (författare)
  • Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy
  • 2014
  • Ingår i: Journal of Experimental & Clinical Cancer Research. - 1756-9966 .- 1756-9966. ; 33
  • 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.
35.
  • Hultman, Bo, et al. (författare)
  • Costs and clinical outcome of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from gastric cancer
  • 2012
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:1, s. 112-121
  • 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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36.
  • Hultman, Bo, et al. (författare)
  • Phase II study of patients with peritoneal carcinomatosis from gastric cancer treated with preoperative systemic chemotherapy followed by peritonectomy and intraperitoneal chemotherapy
  • 2013
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 52:4, s. 824-830
  • 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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37.
  • Hultman, Bo, et al. (författare)
  • Prognostic factors in patients with loco-regionally advanced gastric cancer
  • 2017
  • Ingår i: World Journal of Surgical Oncology. - 1477-7819 .- 1477-7819. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of this study was to investigate epidemiologic and prognostic factors relevant to the treatment of loco-regionally advanced gastric cancer (GC).METHODS: Two hundred and fifty-five patients with GC were identified in Uppsala County between 2000 and 2009. Patient records were analyzed for loco-regionally advanced GC defined as tumor with peritoneal involvement, excluding serosal invasion from the primary tumor only, at primary diagnosis or during follow-up. The presence or not of distant metastasis (DM), including hematogenous metastases (e.g., liver, lung, and bone) and/or distant lymph node metastases, was also analyzed. The Cox proportional hazard model was used for multivariate analysis of factors influencing survival.RESULTS: One hundred and twenty patients (47% of all patients with GC; median age 70.5 years) had loco-regionally advanced disease, corresponding to an incidence of 3.8 per 100,000 person-years. Forty-one percent of these also had DM. Median overall survival (mOS) from the time of the diagnosis of loco-regionally advanced disease was 4.8 months for the total patient cohort, 5.1 months for the subgroup of patients without DM, and 4.7 months for the subgroup with DM. There was no significant difference in mOS between the subgroups with synchronous versus metachronous loco-regionally advanced GC: 4.8 months (range 0.0-67.4) versus 4.7 months (range 0.0-28.3). Using multivariate Cox analysis, positive prognostic factors for survival were good performance status at diagnosis and treatment with palliative chemotherapy and/or radiotherapy. Synchronous DM was a negative prognostic factor. The mOS did not differ when comparing the time period 2000-2004 (5.1 months, range 0-67.4) with the period 2005-2009 (4.0 months, range 0.0-28.3).CONCLUSION: Peritoneal involvement occurred in almost half of the patients with GC in this study and was associated with short life expectancy. New treatment strategies are warranted.
38.
  • Krause, Johan, et al. (författare)
  • Ultrasonography findings and tumour quantification in patients with pseudomyxoma peritonei
  • 2012
  • Ingår i: European Journal of Radiology. - 0720-048X .- 1872-7727. ; 81:4, s. 648-651
  • 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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39.
  • Lorant, Tomas, et al. (författare)
  • Sinus Excision and Primary Closure Versus Laying Open in Pilonidal Disease : A Prospective Randomized Trial
  • 2011
  • Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 54:3, s. 300-305
  • 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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40.
  • Mahteme, Haile, et al. (författare)
  • 5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy or vasoconstriction : an autoradiographic study in the rat
  • 2005
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 25:2A, s. 917-922
  • 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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