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T Roskams

Publications and source records attributed to T Roskams.

At least 19 recordsLinked to original sources
PubMed2006

Transrectal ultrasound in the staging of clinical T3a prostate cancer.

INTRODUCTION: The clinical staging of T3a prostate cancer is usually based on digital rectal examination (DRE). Overstaging of clinical T3a prostate cancer is present in 13-27% of the cases presented and understaging is in the range of 30%. The value of transrectal ultrasound (TRUS) as a staging tool is not generally accepted. The purpose of this study is to determine whether TRUS can refine the local staging in unilateral clinical T3a (cT3a) prostate cancer. PATIENTS AND METHODS: Between 1987 and 2004, 200 patients were staged as unilateral cT3a prostate cancer by DRE. All patients underwent radical prostatectomy and bilateral pelvic lymphadenectomy. Preoperative TRUS staging was performed for all patients. Final histopathological staging was compared with DRE and TRUS staging. The operable group (OG) was defined as T2 to unilateral T3a, and the advanced group (AG) was defined as bilateral T3a to T4. RESULTS: All DRE patients were assumed operable. However, in this group histopathology showed 27.0% of the patients had advanced disease. TRUS confirmed 184 patients to be operable (140 having unilateral cT3a, 44 patients having cT1c to cT2). Sixteen patients were considered to have advanced disease by TRUS. Importantly, in this group, 68.7% of the cases were indeed confirmed to have advanced disease by histopathology. CONCLUSION: TRUS can be used to refine clinical staging in unilateral cT3a prostate cancer. In cases where TRUS indicates advanced disease, it might be wise to trust the TRUS staging, rather than the DRE.

Adult↗
PubMed2006

Liver stem cells and their implication in hepatocellular and cholangiocarcinoma.

In the liver, several cell types have the longevity that is needed to be the cell of origin of a cancer: hepatocytes, cholangiocytes and progenitor cells. The latter are located in the most peripheral branches of the biliary tree, the ductules and canals of Hering. The most important risk factors for liver cancer are chronic viral hepatitis B and C and alcoholic and non-alcoholic steatohepatitis. In these and other chronic liver diseases, progenitor cell activation is seen, rendering them a target cell population for carcinogenesis. The degree of activation is positively correlated with the inflammatory activity and the stage of the disease. Recently, it has been shown that in the cirrhotic stage of most chronic liver diseases, the hepatocytes become senescent owing to telomere shortening. This makes it even more plausible that at least part of the hepatocellular carcinomas originate from a progenitor cell. Hepatocellular carcinomas expressing progenitor cell/ductular markers like cytokeratin 19 have a more aggressive clinical course. It is therefore important to recognize this entity.

Bile Duct Neoplasms↗
PubMed2006

The effect of imatinib mesylate on the contractility of isolated rabbit myometrial strips.

BACKGROUND: C-kit receptor expressing interstitial cells generate and coordinate the electrical signals that control peristalsis in the gut. However, the function of interstitial cells in the myometrium is not known. METHODS: (1) Sections of rabbit myometrium were subjected to immunohistochemical staining for the c-kit receptor. (2) Spontaneously contracting myometrial strips from New Zealand White rabbits near term were mounted in an organ bath and attached to a tension-recording device. The effect of increased concentrations of the c-kit receptor antagonist imatinib mesylate on these contractions was observed. The main outcome measures were the change in frequency, amplitude and duration of contraction. RESULTS: (1) Multipolar cells expressing c-kit were identified in the fibromuscular septum confirming the presence of interstitial cells in rabbit myometrium. (2) Imatinib decreased the amplitude of contractions by approximately 20% at 100 microM. No effect was seen at lower concentrations. No effect of imatinib on frequency or duration of contractions was observed at any of the concentrations studied. CONCLUSIONS: In isolated rabbit myometrium, acute inhibition of the c-kit receptor by imatinib mesylate affects only the amplitude of spontaneous contractions at concentrations, the equivalent of x10-100 the normal therapeutic concentration.

Animals↗
PubMed2006

Value of carbon dioxide wedged venography and transvenous liver biopsy in the definitive diagnosis of Abernethy malformation.

We report a 25-year-old man who presented with congenital absence of the portal vein, or Abernethy malformation, a rare congenital disorder in which the mesenteric and splenic venous drainages bypass the liver and directly drain into the inferior vena cava through an extrahepatic portosystemic shunt. Magnetic resonance imaging, which showed multiple nodular lesions in both liver lobes that were associated with an absence of intrahepatic portal venous branches, strongly suggested the diagnosis of the Abernethy malformation. Carbon dioxide wedged venography and transvenous liver biopsy, which were performed in the same session by a right jugular approach, confirmed these findings. This technique can be considered a valuable alternative diagnostic tool to catheter arteriography and percutaneous transhepatic liver biopsy.

Adult↗
PubMed2006

Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review.

Advanced and metastatic renal cell cancer (RCC) is resistant to conventional chemotherapy. Only a very small number of patients survive long term after immunotherapy. However, any effect of interleukin-2 (IL-2) and/or interferon on median overall survival is small, and treatment-associated toxicities may be severe. The disease is therefore an area of high unmet medical need. Activation of the VEGF and EGF/RAS/RAF/MAP kinase pathways is frequent in solid tumours such as RCC. Such activation is implicated in tumour angiogenesis and proliferation. VEGF and EGF receptors and molecules (such as RAF kinase) involved in downstream signalling are therefore potential appropriate targets for drug therapy. Several antibodies and low molecular weight tyrosine kinase inhibitors (TKIs) have completed phase II clinical trials. Phase II studies of multitargeted agents, which include inhibition of VEGFR tyrosine kinase in their repertoire (sorafenib, sunitinib and AG 013736), show clear second-line activity in metastatic RCC. The same is true of the anti-VEGF antibody, bevacizumab. In a randomised phase III comparison against placebo in pretreated patients, sorafenib doubled median progression free survival (24 versus 12 weeks). Studies now in progress will determine whether benefits seen second-line will also be evident first-line, and whether the activity of novel agents can be increased by combining them with each other, with cytokines, or with chemotherapy.

Antibodies, Monoclonal↗
PubMed2006

A stable model of cirrhotic portal hypertension in the rat: thioacetamide revisited.

BACKGROUND: Cirrhotic animal models are vital to investigate complications of chronic liver disease. We chronologically characterized the effect of thioacetamide, administrated orally and adapted weekly to weight changes, focusing on the optimal moment to obtain all typical features of portal hypertension and cirrhosis. MATERIALS AND METHODS: Male Wistar rats, 200-250 g, were intoxicated for 6, 12 or 18 weeks (n = 8 per group), respectively, and compared with age-matched controls (n = 4 per group). An in-situ perfusion model was used to evaluate intrahepatic resistance and endothelial function. Splanchnic blood flow and portosystemic shunting were assessed by a perivascular flow probe. RESULTS: Rats intoxicated for 6 or 12 weeks had no mortality and histologically showed hepatitis and advanced fibrosis, respectively. At 18 weeks, mortality was 16% (on a total of 56 animals) and only at that moment all animals showed homogenous macronodular cirrhosis with signs of high-grade hepatocellular dysplasia. Portal hypertension was present at 12 weeks (11 +/- 0.4 vs. 5.9 +/- 0.4 mmHg, P < 0.001), but was not associated with the hyperdynamic state until 18 weeks (12.1 +/- 0.8 vs. 5.6 +/- 0.5 mmHg, P < 0.001). At this latter time-point, we also observed increased intrahepatic resistance associated with endothelial dysfunction, hyperresponsiveness to vasoconstrictors, splanchnic hyperaemia and portosystemic shunting. These alterations were associated with increased systemic levels of nitrate/nitrite and thromboxane A(2). CONCLUSION: Thioacetamide, adapted to weekly weight changes, leads to a homogenous, reproducible model of cirrhosis in the rat in 18 weeks, which is associated with all the typical characteristics of portal hypertension, including endothelial dysfunction.

Administration, Oral↗
PubMed2006

The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin.

AIMS: Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients. METHODS AND RESULTS: The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), alpha-fetoprotein (AFP), p53 and beta-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7-/CK19- (72%), 13 CK7+/CK19- (12%), seven CK7-/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) (P = 0.023), tumour AFP expression (P < 0.0001), presence in serum of anti-hepatitis B core (P = 0.016), less fibrosis in non-neoplastic parenchyma (P = 0.009) and less nuclear beta-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear beta-catenin expression (P = 0.003). HCC expressing CK19 had a higher rate of recurrence (P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19- tumours. CONCLUSIONS: In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19- HCC.

Adult↗
PubMed2005

Elucidation of the tumoritropic principle of hypericin.

Hypericin is a potent agent in the photodynamic therapy of cancers. To better understand its tumoritropic behaviour, we evaluated the major determinants of the accumulation and dispersion of hypericin in subcutaneously growing mouse tumours. A rapid exponential decay in tumour accumulation of hypericin as a function of tumour weight was observed for each of the six tumour models investigated, and a similar relationship was found between tumour blood flow and tumour weight. Moreover, there was a close correlation between the higher hypericin uptake in RIF-1 tumours compared to R1 tumours and tumour vessel permeability. To define the role of lipoproteins in the transport of hypericin through the interstitial space, we performed a visual and quantitative analysis of the colocalization of hypericin and DiOC18-labelled lipoproteins in microscopic fluorescent overlay images. A coupled dynamic behaviour was found early after injection (normalised fluorescence intensity differences were on the whole less than 10%), while a shifted pattern in localisation of hypericin and DiOC18 was seen after 24 h, suggesting that during its migration through the tumour mass, hypericin is released from the lipoprotein complex. In conclusion, we were able to show that the tumour accumulation of hypericin is critically determined by a combination of biological (blood flow, vessel permeability) and physicochemical elements (affinity for interstitial constituents).

Animals↗
PubMed2005

Cancer cell dissemination during curative surgery for colorectal liver metastases.

AIM: The amount of cancer cells disseminated during curative surgery for colorectal liver metastases (CRLM) may be responsible for recurrence. Haematogenous and intrahepatic cancer cell dissemination was evaluated, and its impact on cancer recurrence was assessed. METHOD: Twenty patients with resectable CRLM were included in a prospective study. Twelve patients underwent curative resection for 21 metastases. Ten selected metastases in eight patients were treated with radiofrequency ablation (RFA) followed by resection at the same operative session. Cancer cell dissemination was determined before, during and after surgery using 'real time' quantitative RT-PCR assay, based on detection and quantification of CEA and CK20 mRNA transcripts. RESULTS: Circulating cancer cells were detected in 80% and intrahepatic cancer cells in 37% of the patients, though without impact on cancer recurrence. The amounts of disseminated cancer cells were significantly increased after surgery. This increase was similar in patients treated with and without RFA. RFA caused complete tumour destruction. CONCLUSION: Curative surgery for CRLM significantly increases the amount of disseminated cancer cells. Radiofrequency ablation can completely destroy selected resectable CRLM without excessive cancer cell dissemination. Neither haematogenous nor intrahepatic cancer cell dissemination were related to cancer recurrence in this small patient series.

Aged↗
PubMed2005

Nodular regenerative hyperplasia, portal vein thrombosis, and avascular hip necrosis due to hyperhomocysteinaemia.

A male patient with portal hypertension, portal vein thrombosis, spontaneous splenorenal shunt formation, and encephalopathy, thought to have post-hepatitis B cirrhosis, is described. His condition deteriorated and necessitated liver transplantation. In the explant liver, nodular regenerative hyperplasia with pronounced vascular lesions both in portal venules and in arterioles was found instead of classical cirrhosis. Two years post-transplant he developed bilateral ischaemic femur head necrosis. The three disorders (portal vein thrombosis, nodular regenerative hyperplasia, and ischaemic hip necrosis) seemed to be due to a common vasculopathy induced by hyperhomocyteinaemia. Genetic studies showed that he carried a mutation in the gene encoding for formation of methylenetetrahydrofolate reductase. Treatment with folic acid combined with pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) normalised his serum homocysteine levels.

Femur Head Necrosis↗
PubMed2004

Hepatic fibrogenesis requires sympathetic neurotransmitters.

BACKGROUND AND AIMS: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. METHODS: We studied cultured HSC and intact mice with liver injury to test the hypothesis that HSC respond to and produce SNS neurotransmitters to promote fibrogenesis. RESULTS: HSC expressed adrenoceptors, catecholamine biosynthetic enzymes, released norepinephrine (NE), and were growth inhibited by alpha- and beta-adrenoceptor antagonists. HSC from dopamine beta-hydroxylase deficient (Dbh(-/-)) mice, which cannot make NE, grew poorly in culture and were rescued by NE. Inhibitor studies demonstrated that this effect was mediated via G protein coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3-kinase. Injury related fibrogenic responses were inhibited in Dbh(-/-) mice, as evidenced by reduced hepatic accumulation of alpha-smooth muscle actin(+ve) HSC and decreased induction of transforming growth factor beta1 (TGF-beta1) and collagen. Treatment with isoprenaline rescued HSC activation. HSC were also reduced in leptin deficient ob/ob mice which have reduced NE levels and are resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC proliferation, upregulated hepatic TGF-beta1 and collagen, and increased liver fibrosis. CONCLUSIONS: HSC are hepatic neuroglia that produce and respond to SNS neurotransmitters to promote hepatic fibrosis.

Animals↗
PubMed2003

Aggregated colon cancer cells have a higher metastatic efficiency in the liver compared with nonaggregated cells: an experimental study.

BACKGROUND: It remains unclear whether aggregated colon cancer cells have a higher tendency for metastasis formation than nonaggregated cells. Also, the absolute number of cancer cells required for hepatic metastasis remains undefined. The aim of the present study was to compare in the liver the metastatic efficiency of viable nonaggregated colon cancer cells versus cell aggregates for equivalent numbers of cancer cells. MATERIALS AND METHODS: DHD/K12/TRb colon cancer cells were administered through the portal vein in syngeneic male BD IX rats. Surgical exploration was performed 8 weeks after injection. Four groups of rats were injected with 0.25 or 0.5 x 10(6) DHD/K12/TRb viable cancer cells, either as single nonaggregated cells or as cell aggregates. RESULTS: Hepatic metastases were observed in 81% of the rats after intraportal injection of cell aggregates equivalent to 0.5 x 10(6) cancer cells. A significant lower metastatic efficiency was found after the injection of 0.5 x 10(6) non-aggregated, and 0.25 x 10(6) aggregated or nonaggregated cancer cells i.e., 16%, 32%, and 27%, respectively. CONCLUSION: Aggregated colon cancer cells have a higher metastatic efficiency in the liver compared with non-aggregated cells, although a critical number of cancer cells are necessary.

Adenocarcinoma↗
PubMed2003

Is low-grade prostatic intraepithelial neoplasia a risk factor for cancer?

INTRODUCTION: High-grade prostatic intraepithelial neoplasia (HGPIN) is generally accepted to be a precursor lesion of prostate cancer. The likely outcome of isolated low-grade PIN (LGPIN) lesions in prostate biopsies remains unclear. A follow-up study of 106 patients with LGPIN- and HGPIN lesions was performed. MATERIALS AND METHODS: In a 2-y period, 207 men were diagnosed with isolated PIN on standard systematic sextant biopsy of the prostate. In total, 104 patients had LGPIN and 103 had HGPIN. No patients had ever received androgen deprivation therapy, chemotherapy or radiation therapy. In all, 106 patients who underwent repeat second or third sextant biopsies were analysed in the study; 30% of these patients received a selenium-vitamin E supplement for at least 6 months. RESULTS: In total, 43 had LGPIN and 63 HGPIN on the first biopsy. The mean age was 63.5 y (range 46-77) in the LGPIN group and 64.9 y in the HGPIN group. The mean total PSA was 6.96 ng/ml (range 0.59-34.13) in the LGPIN group and 8.44 ng/ml (range 0.59-35.3) in the HGPIN group. In the LGPIN group, 30% of the patients had cancer in at least one of the repeat biopsy cores. In the HGPIN group, 27% had cancer in at least one of the repeat biopsy cores. The mean total PSA of patients who had cancer in repeat biopsies with LGPIN was 7.84 ng/ml (range 2.92-34.13). The mean total PSA of the patients who had cancer in repeat biopsy in the HGPIN was 6.73 ng/ml (range 0.56-25). There was no significant difference in PSA and pathological stage between those patients who did and those who did not receive selenium-vitamin E supplements. CONCLUSIONS: These data are intriguing since the risk of finding prostate carcinoma on repeat sextant biopsy in the LGPIN group is 30%. This is higher than commonly reported. The importance of recognising and re-biopsying HGPIN was confirmed. If chemoprevention could be shown to be effective, it might be beneficial not only in HGPIN but also in LGPIN. The possible activity of chemopreventive agents and their combination with iso-flavonoids needs further investigation.

Aged↗
PubMed2002

Hypericin-based fluorescence diagnosis of bladder carcinoma.

OBJECTIVE: To determine the use of hypericin instillation for the fluorescent detection of papillary bladder cancer and carcinoma in situ. PATIENTS AND METHODS: Eighty-seven patients with papillary bladder cancer and/or carcinoma in situ received instillations with 40 mL of an 8 micromol/L hypericin solution for at least 2 h. Fluorescent excitation with blue light was effective for up to 16 h, and biopsies were examined by fluorescence microscopy. RESULTS: There were no side-effects reported, no photobleaching and all papillary lesions fluoresced red. The sensitivity and specificity for detecting carcinoma in situ was 94% and 95%, respectively. An interval of 4 months is recommended after BCG instillations before using this test. Fluorescence microscopy showed that hypericin was selectively localized in the epithelium. CONCLUSIONS: Hypericin-induced fluorescence has a high sensitivity and specificity for detecting bladder cancer. After 4 months there are few false-positive results in patients treated with BCG.

Anthracenes↗