Biomedical subjects

M Thörn

Publications and source records attributed to M Thörn.

At least 19 recordsLinked to original sources

PubMed2006

Sentinel node lymphocytes: tumour reactive lymphocytes identified intraoperatively for the use in immunotherapy of colon cancer.

The sentinel node is the first lymph node to receive lymphatic drainage from a tumour and is usually the first site of metastases. Today, the sentinel node is used for tumour staging. Here, we focus on its immunological role and investigate lymphocytic function in sentinel nodes, identified intraoperatively by peritumoural dye injection, from 15 patients with colon cancer. Tumour infiltrating lymphocytes, sentinel and nonsentinel lymph node cells and peripheral blood leukocytes were studied by flow cytometry, proliferation assays and interferon-gamma secretion after activation with autologous tumour homogenate. Whereas tumour-infiltrating lymphocytes were nonresponsive in the proliferation assays, lymphocytes from sentinel nodes proliferated dose dependently and secreted interferon-gamma upon stimulation with tumour homogenate. The responses were of varying magnitude and tended to be weaker in metastatic sentinel nodes. Sentinel node lymphocytes represents an enriched source of tumour reactive lymphocytes, and may be useful in future trials of adoptive immunotherapy.

Aged↗

PubMed2005

Identification of sentinel nodes in patients with colon cancer.

AIMS: Lymphatic mapping and sentinel node biopsy entails better staging in malignant melanoma and breast cancer and we used this technique in patients with colon cancer to possibly improve detection of lymphatic spread. METHODS: Thirty patients with invasive adenocarcinomas were investigated. The tumour status in identified sentinel node(s) was compared with the status in all other harvested regional nodes for each patient. Patients were followed at regular visits for more than 30 months. RESULTS: Sentinel nodes were identified in all cases, either per-operatively (28 cases) or at dissection of the formalin-fixed specimen (2 cases). The sentinel nodes were diagnostic for the entire lymphatic field in 28 patients and the false negative rate was 2/12. In four cases, the sentinel nodes were the only metastatic nodes. After at minimum 30 months, three patients had died of colon cancer metastases. CONCLUSION: This method improved the identification of patients with lymph-node metastases, especially those with only few metastatic nodes. Patients dying from metastatic disease had lymph-node metastases at diagnosis.

Adenocarcinoma↗

PubMed2003

[Bladder cancer and the sentinel node concept].

PURPOSE: Lymph node status is one of the most important prognostic factors in muscle-invasive bladder cancer. The extent of lymphadenectomy performed in conjunction with cystectomy and the question as to whether this is a staging or therapeutic intervention are matters of discussion. The aim of this study was to evaluate the sentinel node (SN) concept and to correlate findings with tumour status in excised regional lymph nodes. MATERIAL AND METHOD: 26 patients scheduled for cystectomy were investigated with preoperative lymphoscintigraphy, peroperative dye detection (Patent Blue) and dynamic lymphoscintigraphy (Nanocoll or Albures 50 MBq/ml). The substances were injected adjacent to the tumour in the detrusor muscle. RESULTS: Sentinel nodes were detected in 21 of the 26 of the investigated patients. 7/21 SN were located outside the obturator fossa. Of the eight patients with lymph node metastasis, five displayed metastasis in lymph nodes outside the obturator fossa. There was one false negative SN in a patient with multifocal tumour, while in the other seven patients with lymph node metastasis, these were detected in the SN. CONCLUSION: Sentinel node detection is possible in most cases of bladder cancer scheduled for cystectomy. The significance of utilizing this method to detect lymph node metastasis outside the obturator fossa warrants further investigation.

Cystectomy↗

PubMed2002

Inhibition of bacterial alpha-glucosidases by castanospermine in pure cultures and activated sludge.

Castanospermine (CAST) is a known and potent inhibitor of various alpha-glucosidases in eukaryotes. In this work, we elucidated whether CAST could also be used for determining bacterial alpha-glucosidase activity, when measured with 4-methylumbelliferyl-alpha- D-glucoside as a substrate, both in a complex bacterial community, in activated sludge and in pure cultures of bacterial isolates. We found that 140 microM CAST inhibited alpha-glucosidase activity by 30% in a pure culture of Pseudomonas stutzeri. The alpha-glucosidase activity in Chryseobacterium gleum was inhibited by 90% at a concentration of 150 microM CAST, whereas the alpha-glucosidase in Paracoccus denitrificans was resistant to the inhibitor. CAST (140 microM) reduced alpha-glucosidase activity in activated sludge by 40%, the respiration rate being reduced by only 12%. No significant inhibition of the respiration rate was observed in Ps. stutzeri or Pa. denitrificans, whereas the respiration rate in C. gleum grown in a medium containing starch was inhibited by 50% with 140 microM CAST. No effect of CAST was observed in C. gleum grown in a complex medium. This indicated that CAST, at the concentration used, did not cause a general negative effect on bacterial activity. The results suggest that the CAST assay may potentially be useful in determining whether alpha-glucosidase activity, starch, poly- and disaccharides contribute appreciably to the overall activity of a bacterial community. However, the assay should not be used for quantitative measurements of such activity.

Bacteria↗

PubMed2001

Independent patterns of cytochrome P450 gene expression in liver and blood in patients with suspected liver disease.

OBJECTIVE: Assessment of liver metabolism using blood samples was tested by comparison of cytochrome P450 (CYP) gene expression in paired liver and blood samples from 13 individuals. METHODS: Total RNA was isolated from percutaneous needle biopsies and blood collected simultaneously. Gene expression for CYP1A2, CYP1B1, CYP2E1 and CYP3A4 was studied using a real-time reverse-transcription polymerase chain reaction (RT-PCR) method. RESULTS: All CYP mRNA species were expressed in all liver biopsies but at varying levels. The highest and lowest levels of expression were observed for CYP2E1 and CYP1B1, respectively. The expression patterns differed between blood and liver. CYP1B1 was expressed in all blood samples at a 20% higher level than in the liver. CYP1A2, CYP2E1 and CYP3A4 were expressed in blood at 35- to 5,000-fold lower levels than in liver. None of the transcripts in blood showed any correlation with the expression in liver. CONCLUSION: We conclude that blood cannot serve as a surrogate organ for assessment of the expression of the studied CYP genes in liver.

Adult↗

PubMed2001

IL-5 and TNF-alpha participate in recruitment of eosinophils to intestinal mucosa in ulcerative colitis.

There is an increased influx of activated eosinophils to the intestinal mucosa in active ulcerative colitis, and an increased release of eosinophil-derived proteins, such as ECP, has also been observed. These findings indicate that eosinophils may contribute to tissue damage and intestinal inflammation in this disease. The relative importance of different chemotactic factors and the impact of steroid treatment on their effect in active ulcerative colitis are not known. We measured the eosinophil chemotactic activity in perfusion fluids from 11 patients with ulcerative colitis before and after steroid treatment and from 7 control patients. The effect of neutralizing antibodies to IL-5 and -8, RANTES, eotaxin, MCP-3, TNF-alpha, GM-CSF was investigated. The chemotactic activity was higher in perfusion fluids from patients than from controls (P = 0.0043). Anti-IL-5 (P = 0.005) and -TNF-alpha (P = 0.017) inhibited the activity in perfusion fluids obtained before treatment. Steroid treatment prevented the effect of all antibodies but had no significant effect on the chemotactic activity. The chemotactic activity correlated with the levels of eosinophil granule proteins in the perfusion fluids. In conclusion, in ulcerative colitis, eosinophils are attracted to the intestinal tissue by chemotactic factors, of which IL-5 and TNF-alpha may be the most prominent steroid-sensitive ones. The steroid-insensitive chemotactic activities remain unidentified.

Adult↗

PubMed2001

Multicentre study of detection and false-negative rates in sentinel node biopsy for breast cancer.

BACKGROUND: Sentinel node biopsy has recently evolved as a means of staging the axilla in breast cancer with minimal surgical trauma. The aim of this prospective multicentre study was to identify factors that influenced the detection and false-negative rates during the learning phase. METHODS: Data on all 498 sentinel node biopsies performed between August 1997 and December 1999 in Sweden were collected. RESULTS: A sentinel node was found in 450 patients (90 per cent). Preoperative scintigraphy visualized 83 per cent of all sentinel nodes. The detection rate was higher with same-day injection of tracer than with injection the day before (96 versus 86 per cent; P < 0.01). Dye injected less than 5 min or more than 30 min before the start of the operation lowered the detection rate (less than 60 per cent versus more than 65 per cent; P = 0.02). The detection rate varied from 61 to 100 per cent between surgeons. The false-negative rate was 11 per cent. The presence of multiple tumour foci and a high S-phase fraction increased the risk of a false-negative sentinel node, whereas the number of operations performed by each surgeon was less important. CONCLUSION: Training of the individual surgeon influenced the detection rate, as did timing of tracer and dye injection. The false-negative rate seemed to be related to biological factors.

Adult↗

PubMed2001

Sentinel node in breast cancer--a Swedish pilot study of 75 patients.

OBJECTIVE: To find out if the sentinel node can be detected in sufficient numbers of women with breast cancer to be useful as a prognostic sign, whether it reflects that state of the entire axilla, and whether it detects micrometastases that would otherwise be missed. DESIGN: Prospective study. SETTING: 3 teaching hospitals, Sweden. SUBJECTS: 75 patients with breast cancer who were listed to have axillary dissection as well as resection of their tumour. INTERVENTIONS: Injection of 99Tc nanocolloid 0.4 ml and patent blue dye 1 ml around the tumour or under the skin above the tumour, followed by preoperative lymphoscintigraphy and then identification of the sentinel node during operation either because it had turned blue or with a gamma probe. Removal of the sentinel node and complete axillary dissection. MAIN OUTCOME MEASURES: Identification of the sentinel node and presence of metastatic nodes in the axilla. RESULTS: The sentinel node was identified in 69/75 (92%). It correctly predicted the state of the axilla in 66/69 (96%), and detected metastases in 24 of the 27 with invaded nodes in the axilla (89%). The false negative rate was 11%. In 14/27 with axillary metastases (52%) the sentinel node was the only involved node. In 3/24, metastases were detected by immunohistochemistry alone. CONCLUSION: Biopsy of the sentinel node predicted the presence or absence of axillary metastases with acceptable accuracy. However, before axillary node dissection is rejected in favour of sentinel node biopsy alone, large multicentre studies are needed to establish the true false negative rate.

Adult↗

PubMed2001

Neutrophil and eosinophil granule proteins as markers of response to local prednisolone treatment in distal ulcerative colitis and proctitis.

OBJECTIVE: The pathophysiological role of neutrophil and eosinophil granulocytes in relation to steroid enema treatment was studied in patients with distal ulcerative colitis and proctitis. METHODS: The rectal release of the neutrophil (myeloperoxidase, MPO), and eosinophil (eosinophilic cationic protein, ECP and eosinophil peroxidase, EPO) granule constituents were measured in 11 patients using intraluminal segmental perfusion of the rectum. The released amounts of MPO, ECP, and EPO in the perfusion fluids were determined by radioimmunoassays before and during prednisolone enema treatment and related to clinical, endoscopical, and histopathological data in addition to treatment outcome. RESULTS: Clinical activity and particularly endoscopic activity correlated well with intraluminal MPO concentrations both before and during treatment. At the end of the study, eight of 11 patients fulfilled predefined response criteria; all responding patients had significant decrease of MPO concentrations (p < 0.01). This decline of MPO concentration was seen after 7 days of treatment (p < 0.05) in the response group and often occurred before clinical improvement. There was a nonsignificant trend toward a decrease in the concentrations of ECP and EPO at the end of treatment in responders.

Administration, Topical↗

PubMed2001

Lymphatic mapping and detection of sentinel nodes in patients with bladder cancer.

PURPOSE: We examined the possibility for detecting sentinel nodes in patients with bladder cancer and whether the histopathological status of identified sentinel nodes reflected that of the lymphatic field. MATERIALS AND METHODS: A total of 13 patients with bladder cancer who met the criteria qualifying them for radical cystectomy had intravesical injections of radioactive tracer and blue dye marker around the tumor followed by lymphoscintigraphy to visualize lymphatic drainage and detect sentinel nodes. Sentinel nodes were identified preoperatively by the blue color and increased radioactivity and were compared histopathologically with other routinely excised lymph nodes. RESULTS: Sentinel nodes were detected in 85% (11 of 13) of patients. There were 4 patients who had sentinel nodes containing tumor cells, and each metastasis was only seen in the detected sentinel node. There were no false-negative sentinel nodes. Of the metastatic sentinel nodes 3 were located outside the normally excised lymph nodes of the obturator fossa. CONCLUSIONS: Sentinel nodes can be detected in patients with bladder cancer. The histopathological status of the identified sentinel nodes was diagnostic for all other excised lymph nodes. Sentinel nodes often seem to be located outside the obturator lymphatic field, which is normally examined during preoperative staging of bladder cancer.

Adult↗

PubMed2000

Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EBBeta) and C/EBzeta (CHOP) correlate with invasiveness of human colorectal cancer.

Regulation of cell differentiation is most often impaired in malignant tumors and may represent a key mechanism for the progression of the disease. CCAAT-enhancer binding protein (C/EBP) is a family of transcription factors involved in the regulation of embryonic gut development in rodents, which has also been detected in various malignancies, e.g., liposarcomas and breast and ovarian epithelial tumors. We studied the relationship between C/EBP and tumor histology (Duke's invasive stage and pathological grade) in colorectal cancer. Immunoblotting techniques were used on microdissected fresh frozen tumor specimens, and expression of C/EBPalpha, C/EBPbeta and C/EBPzeta (CHOP) was analyzed in addition to that of the cell-cycle regulator p53 and the proliferation marker PCNA. Expression of C/EBPbeta (LAP isoforms) was markedly increased in all tumors compared with normal colon mucosa. Although the inter-patient variability was large, we found that LIP, the isoform of C/EBPbeta known to inhibit transcription, was expressed at higher levels in Duke's stage B tumors compared with Duke's stage A, whereas Duke's C tumors had the lowest LIP expression. A similar relationship was seen for CHOP. The cell-cycle regulator gene p53 was the only factor that clearly correlated with pathological grade: a decrease in p53 expression was demonstrated. Our data suggest that genetic and cellular events involving C/EBPbeta and CHOP are important for tumor invasion and that these events do not appear to be related to the pathological grade of the tumor.

Aged↗

PubMed2000

Factors influencing the functional outcome of restorative proctocolectomy in ulcerative colitis.

BACKGROUND: Restorative proctocolectomy is considered to be the procedure of choice in the operative treatment of ulcerative colitis. The aim of this study was to evaluate the functional outcome following operation and to identify possible predictive factors. METHODS: Some 168 patients (median age 32 years, 102 men) with ulcerative colitis underwent restorative proctocolectomy. The functional outcome was evaluated by a symptom index created from a questionnaire at a median of 29 (13-123) months of follow-up. The records of these patients were reviewed, and preoperative, peroperative and postoperative variables were registered and related to outcome. RESULTS: The response rate to the questionnaire was 155 (92 per cent) of 168. The symptom index was related to patients' overall assessment of outcome. In spite of a perceived good result many patients experienced a number of symptoms. Age over 50 years (P < 0.01), presence of extraintestinal manifestations (P < 0.05) and late complications, such as anastomotic stricture (P < 0.05), pouchitis (P < 0.01) and anal pain (P < 0.05), were related to a less favourable outcome. CONCLUSION: While preoperative data may help in selecting patients suitable for restorative proctocolectomy, prevention of late complications seems most important in improving the functional outcome.

Adolescent↗

PubMed2000

Intestinal mucosal secretion of basic fibroblast growth factor in patients with ulcerative colitis.

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes angiogenesis and several other biologic processes, including proliferation of mesenchymal cells and tumor progression. We investigated whether bFGF could be detected in the intraluminal secretion of the small intestine, sigmoid colon, and rectum in healthy individuals and in patients with ulcerative colitis. METHODS: We used endoscopic perfusion techniques to obtain samples from well-defined intestinal segments. The perfusion fluid concentrations of bFGF, biochemical markers of inflammation, myeloperoxidase (MPO), interleukin-6 (IL-6), and permeability (albumin) were determined with immunochemical methods. RESULTS: In the perfusion fluids the albumin concentration, which reflects passive diffusion, was less than 1% of the plasma concentration, whereas the intestinal concentration of bFGF was similar to that in plasma. Among healthy subjects the concentration of bFGF was eightfold higher in the jejunum and twofold higher in the rectum than in the sigmoid colon. The perfusion fluid from colorectal segments in patients with ulcerative colitis had a significantly higher mean concentration of bFGF than that from healthy individuals; an almost 10-fold difference was found in rectal segments. There were strong correlations between the concentration of bFGF and the concentrations of MPO and IL-6. CONCLUSIONS: The high concentrations of bFGF in the intestinal perfusion fluid reflect either a local synthesis or an active secretion of bFGF within the mucosa. The bFGF concentration differs in intestinal anatomic location and increases significantly in patients with ulcerative colitis in close relationship with biochemical markers of inflammation and permeability.

Adult↗

PubMed2000

Lymphatic mapping and sentinel node biopsy: is the method applicable to patients with colorectal and gastric cancer?

The current status of lymphatic mapping and sentinel node biopsy in the treatment of patients with malignant melanoma and breast cancer is described. The possible use of a similar method in patients with colorectal and gastric cancer is outlined. Peroperative lymphatic mapping and identification of sentinel node(s) in patients with gastrointestinal cancer may lead to modified (tailored) resections and extended lymph node dissections only in those patients in whom the sentinel node(s) contains tumour cells. The method offers the possibility of improving staging by identification of patients with early disseminated disease who should be considered for adjuvant treatment or be included in trials of adjuvant treatment to speed up the breakthrough of more effective adjuvant regimens. Large studies are needed to find out if the sentinel node concept is as valid in gastrointestinal cancer as studies so far have shown that it is for malignant melanoma and breast cancer.

Breast Neoplasms↗

PubMed1999

Cancer risk in patients with earlier diagnosis of cutaneous melanoma in situ.

We calculated the short-term and long-term risks of developing cancer among 3,766 patients with a diagnosis of cutaneous melanoma in situ in Sweden from 1958 to 1992. In total, 393 patients developed a primary cancer at any site compared with an expected number of 177 [standardized incidence ratio (SIR) = 2.2, 95% confidence interval (CI) = 2.0-2.4]. Patients below 60 years of age at diagnosis had the highest SIR (2.7, 95% CI = 2.3-3.2). The overall risks were similar between men and women. The highest risk was seen during the first year of follow-up, though the risk remained elevated also after 15 or more years of follow-up. For specific sites, the highest SIR was found for developing invasive cutaneous malignant melanoma (SIR = 22.2). The risk of subsequent primary non-melanoma skin cancer was elevated 8-fold in men and almost 7-fold in women. An elevated risk was also found for female breast cancer (SIR = 1.4). Especially among women, other sites with increased cancer risk (though not significant) were non-Hodgkin's lymphoma (SIR = 1.9), multiple myeloma (3.2) and cancers of the colon (1.6) and pancreas (1.6). In conclusion, patients with melanoma in situ run a generally increased risk of developing primary cancers, especially cutaneous malignant melanoma and non-melanoma skin cancer. The increased long-term risk of cancer after diagnosis of melanoma in situ may be due to continuing carcinogenic exposure or to intrinsic tumor susceptibility.

Adult↗

PubMed1999

Second primary cancers in patients with squamous cell carcinoma of the skin: a population-based study in Sweden.

We studied second primary cancer among 25,947 patients diagnosed with squamous cell carcinoma of the skin (SCC) in Sweden between 1958 and 1992. In total, 5,706 patients developed a second primary cancer at any site, compared with an expected number of 2,651 [standardized incidence ratio (SIR) = 2.15; 95% confidence interval (CI) = 2.10-2.21]. Men below 60 years of age at diagnosis of SCC had higher SIR (2.5; CI = 2.2-2.8) with the highest risk during the first year of follow-up (SIR = 9.2; CI = 6.9-12.2). If second primary SCC was excluded, the SIR was reduced to 1.30 (CI = 1.25-1.34); the relationships by sex, age and time since diagnosis remained similar. For skin cancer, the SIR for second SCC was markedly elevated (SIR = 15.6) and the risk of malignant melanoma was elevated 3-fold. Significantly increased risks were found for most second cancers in squamous cell epithelium: lip (SIR = 5.2), respiratory organs (SIR = 1.7), esophagus (SIR = 1.5), cervix uteri (SIR = 2.2), and vulva including vagina (SIR = 2.3). There was a generally increased risk of almost 2-fold for second cancer in hematopoietic or lymphoproliferative tissues. Slightly increased rates (SIR = 1.0-1.5) were seen for second tumors in digestive tissues. Finally, a high SIR (SIR = 5.5) was observed for second primary cancer in salivary glands. In conclusion, patients with SCC are at increased risk to develop new primary cancer, especially in skin, squamous cell epithelial and tobacco-related tissues. Common risk factors among the tumor types might explain our findings, however, an intrinsic susceptibility among SCC patients to develop cancer is also possible.

Age Distribution↗

PubMed1999

Quantitation of cytochrome P450 mRNAs in patients with suspected liver diseases as assessed by reverse transcriptase-polymerase chain reaction.

The cytochrome P450 system (CYP) is vital for the oxidation and detoxification of numerous drugs and other xenobiotics in the liver. Many of the CYP enzymes are polymorphically expressed and may be induced or inhibited by xenobiotics including drugs and alcohol. The measurement of gene expression is thus important in studies of the mechanisms of interaction with and function of the CYP system. We have developed a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method for the study of the mRNA expression of three CYP enzymes--2E1, 1A2, and 3A4--in snap-frozen percutaneous liver biopsy samples. The method was made quantitative by the introduction of a recombinant RNA internal standard that contains a transcript of the beta-globin gene and sequences specific for the studied CYP enzymes. The method allows the analysis of mRNA expression of several enzymes in as little as 5 mg of liver tissue. Liver tissue specimens from 19 patients with suspected liver disease were analyzed for CYP-specific mRNA expression. The mean mRNA concentrations for CYP1A2, 2E1, and 3A4 were 0.16, 0.74, and 0.32 amol of specific mRNA per nanogram of poly (A+) mRNA, respectively, but a large interindividual variation was observed. CYP3A7 primers were included in the internal standard. However, because of low expression it was not possible to quantitate the enzyme. This quantitative RT-PCR method is of value for studies of the mechanisms of variation and interactions with the members of the CYP enzyme family in healthy and diseased liver and other organs.

Cytochrome P-450 Enzyme System↗

PubMed1998

Trends in colorectal cancer incidence in Sweden 1959-93 by gender, localization, time period, and birth cohort.

OBJECTIVES: This study examined invasive colorectal cancer incidence-rates in Sweden from 1959 through 1993 (n = 134,643 cases). METHODS: Age-standardized rates were calculated using the Swedish population in 1970 as a reference. RESULTS: In right-sided colon cancer (ascending and transverse colon including right and left flexures), male age-standardized rates rose from 8.0 to 15.0 (1.8 percent annually, 95 percent confidence interval [CI] = 1.3-2.4) and female rates increased from 9.1 to 14.4 (1.5 percent annually, CI = 1.0-2.0). For left-sided colon cancer (descending and sigmoid colon), the rates have been stable recently. For rectal cancer, the rates among men rose from 18.8 to 23.0 and among women from 10.7 to 14.7. For both men and women, the relative risk (RR) of right-sided colon cancer had been increasing in successive generations, until leveling-off in those born after 1930. The RR of left-sided colon cancer had been almost constant for cohorts born before 1930 but steadily decreasing in later-born cohorts. The RR of rectal cancer was slightly increasing in successive cohorts. CONCLUSIONS: Changes in lifestyle or carcinogenic exposures during early life probably explain Swedish colorectal cancer incidence-trends better than improved diagnostic activities.

Adult↗