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Per-Uno Malmström

Publications and source records attributed to Per-Uno Malmström.

33 records · Page 2Linked to original sources
PubMed2004

HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancer.

The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data. HER-2, EGFR and COX-2 overexpressions were demonstrated in 15%, 30% and 40% of the tumours, respectively. In adenocarcinomas, HER-2 and COX-2 overexpression were more common, whereas in squamous cell carcinomas, EGFR overexpression was more common. COX-2 expression correlated with HER-2 expression (p = 0.002), and demonstrated a trend towards a correlation with microvessel density (p = 0.10). None of the markers alone had any impact on survival. However, HER-2+/EGFR- tumours proved to have a poor prognosis. In conclusion, adjuvant treatment with HER-2 antagonists might be a future treatment option in resected non-small cell lung cancer patients, especially when HER-2 is overexpressed without a concomitant overexpression of EGFR.

Adult↗
PubMed2004

Advances in intravesical therapy of urinary bladder cancer.

The aim of urinary bladder cancer treatment with intravesical therapy is threefold: to eradicate existing disease, prevent recurrence and prevent tumor progression. The prognostic factors allow differentiation in different risk groups and this is useful in planning treatment. Pharmacokinetic studies have proved the efficacy of a high urine concentration of the chemotherapeutic agent. Comparing resection with and without adjuvant intravesical chemotherapy, an approximately 15% short-term decrease in tumor recurrence with chemotherapy is obtained, although no effect on progression was proven. No chemotherapeutic agent has proved more effective than the other. The importance of early administration has been highlighted by the positive results of a single, early instillation of chemotherapy, with a reported mean reduction in recurrence rate of 12-27%. Immunotherapy in the form of bacillus Calmette-Guerin has generally proven more efficious than chemotherapy. The results in comparison with mitomycin C have not been as conclusive. The best results are found with a maintenance schedule. In this review, several new approaches are explored to improve the efficacy of this therapy.

BCG Vaccine↗
PubMed2003

[Time to stop testing adults for microhematuria].

This study compares recently published reports with earlier literature on asymptomatic microhematuria in order to determine which conditions we wish to diagnose using a dipstick, how effective the test is in a high risk population, which clinical significance a positive test result has as compared to a negative result, and which diagnostic value the test has in the workup of patients with urinary tract symptoms. The conclusion is that testing for microhematuria does not meet the requirements of a modern screening and diagnostic test. Better alternatives are presently available, and in the near future we will likely see urine tests for specific clinical conditions.

Adult↗
PubMed2003

Intravesical therapy of superficial bladder cancer.

The aim of treatment of superficial bladder cancer with intravesical therapy is threefold: (1) Eradicate existing disease. (2) Prevention of recurrence. (3) Prevention of tumor progression. The prognostic factors allow differentiation in different risk groups and this is useful in planning treatment. Studies on pharmacokinetics have proved the efficacy of optimized drug delivery. Comparing resection with and without intravesical chemotherapy a short term approximately 15% decrease in tumor recurrence with chemotherapy can be obtained but no effect on progression was proven. No agent has proved more effective than the other. Single, early instillation of chemotherapy has proven effective but the role of maintenance therapy has been controversial. Immunotherapy in the form of Bacillus Calmette-Guerin generally have proven more efficacious than chemotherapy. The results in comparison to mitomycin C have not been as conclusive. Several new approaches are explored to improve the efficacy of this therapy.

Administration, Intravesical↗
PubMed2003

Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer--a multicenter study.

PURPOSE: We examined the sensitivity and specificity of Hexvix (PhotoCure ASA, Oslo, Norway) hexyl aminolevulinate (HAL) fluorescence cystoscopy in patients with superficial bladder cancer. MATERIALS AND METHODS: A total of 52 patients (38 men and 14 women) with a mean age of 72 years were investigated. HAL hydrochloride (100 mg dissolved in 50 ml phosphate buffer solution) (8 mM) was instilled into the bladder 1 hour prior to the endoscopic procedure. Cystoscopy was performed with the Storz D-light (Karl Storz, Tuttlingen, Germany) system, allowing inspection of the bladder wall under white and blue light (380 to 450 nm). RESULTS: A total of 422 biopsies obtained in fluorescing (165) and nonfluorescing (257) areas, including 5 random biopsies per patient, were analyzed to provide the best reference for the calculation of sensitivity and specificity. There were a total of 143 histologically verified tumors in 45 patients, including carcinoma in situ (CIS), Ta or T1 lesions. A total of 43 patients were diagnosed by fluorescence cystoscopy compared with 33 diagnosed by white light for 96% and 73% per-patient sensitivity, respectively. HAL cystoscopy was found particularly useful for finding CIS tumors. Of 13 patients with CIS tumors all except 1 were diagnosed or confirmed by HAL cystoscopy. HAL cystoscopy was well tolerated with no definite drug related adverse events reported, including effects on standard blood parameters. CONCLUSIONS: HAL fluorescence cystoscopy is a new, sensitive, promising diagnostic procedure that showed improved detection of bladder tumors, in particular CIS. The procedure is well tolerated and can easily be implemented in current clinical practice.

Aged↗
PubMed2003

Zinc-based fixative improves preservation of genomic DNA and proteins in histoprocessing of human tissues.

Advantageous preservation of histology and detailed cellular morphology has rendered neutral buffered formalin (NBF) the most widely used fixative in clinical pathology. Despite excellent morphology for routine diagnostics, a major drawback of NBF fixation is its detrimental effect on DNA and RNA quality. In addition to complicating analysis of genes and transcripts in complex tissues, NBF denatures proteins and thereby hampers immunohistochemical visualization of certain antigens. In the present study, we evaluated a zinc-based fixative (ZBF) regarding its effects on tissue morphology, quality of genomic DNA, and preservation of protein immunoreactivity in a broad spectrum of tissues. Four different modes of fixation were analyzed: ZBF-paraffin embedding, NBF-paraffin embedding, ZBF-fixation prior to snap-freezing, and immediate snap-freezing. Laser-assisted microdissection, allowing retrieval of a defined number of cells for PCR, was used to study DNA quality. Genomic DNA was analyzed using primers for beta2-microglobulin and the transferrin receptor. Immunohistochemistry was performed using nine antibodies. Tissue microarray blocks were used for analysis of morphology and immunoreactivity. Only slight impairment of morphologic qualities was found after ZBF-paraffin embedding, whereas ZBF prior to freezing resulted in a more crisp morphology compared with routine cryosections. A significantly higher DNA yield was observed in samples isolated from ZBF-paraffin-embedded tissues compared with NBF-paraffin-embedded tissues. Both yield and quality of DNA was comparable in frozen tissues irrespective to prior ZBF fixation. Immunoreactivity in paraffin-embedded tissue was superior in ZBF-fixated tissue compared with NBF-fixated for a majority of tested antibodies. Furthermore, for seven out of nine antibodies, antigen retrieval pretreatment proved unnecessary in ZBF-fixated tissue. Thus, despite a slight impairment of morphology, ZBF preserves protein structures well. We conclude that ZBF is superior to NBF for analysis of DNA and protein expression. Fixation of tissues in ZBF may also be an alternative strategy to freeze storage of tissue specimens, eg, in future bio-banks.

Carcinoma, Transitional Cell↗
PubMed2002

Early metastatic progression of bladder carcinoma: molecular profile of primary tumor and sentinel lymph node.

PURPOSE: We characterized early metastatic progression of bladder carcinoma from the primary tumor, separated in the central part and invasive front, to the first lymphatic metastasis. MATERIALS AND METHODS: Included in this study were 8 patients undergoing sentinel lymph node detection for invasive bladder cancer, of whom 4 had metastasis in the sentinel lymph node and 4 were randomly chosen without metastases. After microdissection p53 genomic structure and immunohistochemical expression of p53, pRB, Ki67 and E-cadherin were analyzed. Microvessel density and apoptosis were also assessed. RESULTS: In 5 patients there were p53 gene mutations in the primary tumor, while 3 had the wild-type gene. The genotypes were identical in the central part and invasive front. All sentinel lymph node metastases harbored p53 mutations, in contrast to all nonmetastatic sentinel lymph nodes. Two patients had the same mutation as the primary tumor and 1 had an additional mutation. In a patient with a wild-type gene in each compartment of the primary tumor a mutation appeared in the corresponding sentinel lymph node metastasis. There was poor concordance of p53 mutation with protein status. The expression of p53, pRB, Ki67, E-cadherin, and the evaluation of apoptosis and angiogenesis showed in most cases only slight variations in tumor compartments and the sentinel lymph node. CONCLUSIONS: In this study invasive bladder carcinoma involved monoclonal proliferations with a mainly homogenous biomarker profile. The first metastases in sentinel lymph nodes had a similar molecular profile but in half of the cases signs of clonal evolution appeared.

Apoptosis↗
PubMed2002

Guidelines on bladder cancer.

OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of bladder cancer patients were established. Criteria for recommendations were evidence based, and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS: TNM 1997 classification and WHO grading 1998 are recommended. Recommendations are developed for diagnosis for bladder cancer in general, treatment of superficial and infiltrative bladder cancer, and follow-up after different types of treatment modalities, such as intravesical instillations, radical cystectomy, urinary diversions, radiotherapy and chemotherapy.

Follow-Up Studies↗
PubMed2002

A randomized comparative dose-ranging study of interferon-alpha and mitomycin-C as an internal control in primary or recurrent superficial transitional cell carcinoma of the bladder.

OBJECTIVE: To compare, in a phase II study, the activity and toxicity of three dose levels of interferon-alpha, and of mitomycin-C given intravesically (as an internal control to validate the results), the primary objective being to investigate the percentage of complete responses (complete disappearance of a marker lesion) induced by the three interferon-alpha dose levels on a marker lesion; a secondary objective was to compare the interferon-alpha doses for toxicity. PATIENTS AND METHODS: In all, 115 patients were enrolled, with the inclusion criteria being multiple grade 1 or 2, stage Ta or T1, primary or recurrent transitional cell carcinoma of the bladder. Interferon-alpha (30, 50 and 80 MU) and mitomycin-C (40 mg) intravesical treatments were given as follows. Patients randomized to one of three interferon-alpha dose levels were treated weekly for 12 weeks. However, in week 9 (first cystoscopy after baseline) interferon-alpha treatment was stopped if there was a complete response or disease progression. Patients randomized to mitomycin-C were treated weekly for 8 weeks only and in week 9 underwent follow-up cystoscopy. RESULTS: Interferon-alpha at doses of 30, 50 and 80 MU gave response rates at 13 weeks of 19%, 33% and 41%, respectively. Although the response rates were higher for 50 and 80 MU than for 30 MU, the differences were not statistically significant. All three interferon-alpha groups had significantly lower response rates than the internal control, mitomycin-C (72%). The safety analysis showed that most of the adverse events were of mild to moderate severity. Adverse events were experienced by 37%, 37% and 48% of patients receiving 30, 50 and 80 MU interferon-alpha, respectively, and by 55% of patients receiving mitomycin-C. The corresponding rates for severe adverse events related to treatment were 9% for interferon-alpha and 10% for mitomycin-C. CONCLUSION: Ablative therapy with interferon-alpha was less effective than mitomycin-C in patients with superficial bladder cancer. Both drugs were well tolerated, although interferon-alpha appeared to have a slightly better overall safety profile.

Adult↗
PubMed2002

Neoadjuvant cisplatin-methotrexate chemotherapy for invasive bladder cancer -- Nordic cystectomy trial 2.

BACKGROUND: In the first Nordic cystectomy trial (1986-1989) a chemotherapy combination of cisplatin-doxorubicin and external radiation seemed to improve the long-term survival after cystectomy in patients with stage T3-T4a bladder carcinomas. The aim of this study was to investigate if solely neoadjuvant chemotherapy could influence survival in patients with advanced urothelial bladder cancer undergoing cystectomy. METHODS: The study (1991-1997) recruited 317 patients with T2-T4aNXM0 urothelial bladder tumours. The patients were randomly allocated to three courses of cisplatin-methotrexate or no pretreatment before cystectomy, eight were subsequently excluded due to protocol violation. RESULTS: Chemotherapy according to protocol was administered to 74% (115/155) of the patients in the experimental arm. No chemotherapy related mortality was observed. Of remaining patients in the experimental arm, 14 did not receive any chemotherapy, nine discontinued after one course and 14 after two courses due to side effects. Median follow-up time among censored patients was 5.3 years. Estimated 5-year overall survival was 53% in the experimental arm and 46% in the control arm (n.s. log-rank test). The proportion of patients with pathological stage pT0 was 26.4% in the experimental arm and 11.5% in the control arm (p = 0.001). Risk of locoregional relapse and distant metastases was similar in the study arms. CONCLUSIONS: The chemotherapy regimen was well tolerated. Despite substantial downstaging no statistically significant survival benefit with the neoadjuvant therapy could be seen after 5 years of follow-up.

Adult↗
PubMed2002

HER-2--a possible target for therapy of metastatic urinary bladder carcinoma.

Human epidermal growth factor receptor 2, HER-2, is overexpressed in various tumours, e.g. breast- and bladder tumours. The aim of this study was to predict the potential use of HER-2 receptors as targets in systemic treatment of disseminated bladder tumours. HER-2 expression was assessed in bladder carcinoma metastases and the corresponding primary tumours, and subsequently compared with the EGFR expression. HER-2 and EGFR expression was analysed by immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 21 patients with metastatic bladder carcinoma. HER-2 was overexpressed in 81% of the primary tumours and in 67% of the metastases. All HER-2-positive metastases were from HER-2-positive primary tumours. The results for EGFR were 71% of both primary and metastases-positive tumours. In 90% of the primary tumours and 86% of the metastases, at least one of the receptors was overexpressed. These results suggest that HER-2 targeted therapy can be considered as an alternative or a complement to other modalities in the treatment of metastatic urinary bladder carcinoma.

Aged↗