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M Koch

Publications and source records attributed to M Koch.

At least 109 records · Page 6Linked to original sources

Detection of isolated disseminated tumor cells in bone marrow and blood samples of patients with hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often develop recurrences after curative resection or liver transplantation. Therefore, tumor cell dissemination must have occurred preoperatively or intraoperatively. Current staging methods cannot reliably detect micrometastasis. Reverse transcription-polymerase chain reaction (RT-PCR) for alpha-fetoprotein (AFP) has been used to detect circulating liver cancer cells, but results in blood samples have been contradictory. HYPOTHESIS: AFP-RT-PCR is a specific and sensitive assay for the detection of disseminated tumor cells in central venous blood and bone marrow samples of patients with HCC and has prognostic relevance. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: We performed preoperative, intraoperative, and postoperative analyses of central venous blood samples and preoperative analysis of bone marrow samples of patients with HCC and patients without malignant disease, using a modified AFP-RT-PCR method. Preoperative serum AFP levels were measured. Clinical follow-up ranged from 4 to 20 months. MAIN OUTCOME MEASURES: Sensitivity and specificity of AFP-RT-PCR, correlation of AFP-RT-PCR results to tumor stage and tumor recurrence. RESULTS: In serial dilution experiments, 50 AFP-expressing HepG2 cells were detected in 10 mL of blood. Peripheral blood samples of 20 healthy volunteers and bone marrow samples of 21 patients with benign diseases consistently tested negative for AFP, whereas 4 of 24 patients with HCC showed AFP expression in bone marrow samples. All these patients had advanced disease; however, correlation of positive RT-PCR results to tumor stage was not significant (P = .07). One of the 4 AFP-positive patients developed an intrahepatic recurrence soon after liver transplantation. Central venous blood of patients with HCC (n = 24) and patients with benign liver diseases (n = 13) equally demonstrated AFP-expressing cells. There was no correlation of RT-PCR results to serum AFP levels. CONCLUSIONS: Perioperative screening for micrometastasis in bone marrow of patients with HCC is sensitive and specific with AFP-RT-PCR and may have prognostic relevance. Alpha-fetoprotein is not a suitable marker for the detection of tumor cells in central venous blood samples.

Bone Marrow↗

[Detection of isolated disseminated tumor cells of colorectal carcinomas in lymph nodes].

The 5-year survival of patients with colorectal cancer UICC stage I and II ranges from 70% to 80%. Therefore, at least 20% to 30% of these patients develop recurrent disease, caused by hematogenic or lymphogenic tumor cell dissemination. Using immunohistochemical or molecular biological methods, disseminated tumor cells can be detected in lymph nodes in a high proportion of patients in UICC stage I or II. The detection of disseminated tumor cells could help to identify a subgroup of patients at risk for disease relapse who could benefit from adjuvant therapy. Lymphogenic tumor cell dissemination seems to be a very common event in early colorectal cancer, preceding hematogenic tumor cell dissemination. Although these observations appear to confirm the therapeutic importance of meticulous lymph node dissection, their prognostic relevance has yet to be determined in prospective studies.

Colorectal Neoplasms↗

The tumour necrosis factor alpha -238 G --> A and -308 G --> A promoter polymorphisms are not associated with insulin sensitivity and insulin secretion in young healthy relatives of Type II diabetic patients.

AIMS/HYPOTHESIS: Tumour necrosis factor-alpha (TNF-alpha) is believed to influence skeletal muscle insulin resistance. Two G --> A transitions in the promoter region of TNF-alpha at position -238 and -308 have been identified that could play a part in transcriptional regulation of the gene. Insulin resistance is an independent familial trait that predicts the development of Type II (non-insulin-dependent) diabetes mellitus. We investigated the influence on insulin sensitivity and insulin secretion of both polymorphisms in a cohort of young healthy relatives of patients with Type II diabetes. METHODS: We examined 109 first-degree relatives of Caucasian patients with a history of Type II diabetes, who underwent extensive metabolical and anthropometrical phenotyping, and determined the TNF-alpha -238 and -308 G --> A promoter polymorphisms. RESULTS: For the -238 polymorphism, 3 probands (76.1%) were homozygous for the G-allele, 25 probands (22.9%) were heterozygous and 1 proband (0.9%) was homozygous for the A-allele. For the -308 polymorphism, 83 probands (76.1%) were homozygous for the G-allele, 24 probands (22.0%) were heterozygous and 2 probands (1.18%) were homozygous for the A-allele. Probands with and without the polymorphism did not differ in insulin sensitivity (p = 0.78), insulin-concentrations and C-peptide concentrations in oral glucose tolerance tests (p > 0.05). CONCLUSIONS/INTERPRETATION: We could not detect an association between insulin sensitivity or insulin secretion and TNF-alpha promoter polymorphisms in our cohort. The polymorphisms occur at the same frequencies in probands with either low or high insulin sensitivity.

Adult↗

Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance.

Functional long-term allograft survival after experimental small bowel transplantation (SBT) is limited by chronic rejection. Initial application of high-dose FK 506 has been shown to induce stable long-term graft function. In order to examine whether this long-term function is associated with donor-specific tolerance, we analyzed the functional status of recipient T cells in vivo and in vitro. One-step orthotopic SBT was performed in the allogeneic Brown Norway (BN)-to-Lewis rat strain combination. FK 506 was given daily at a dose of 2 mg/kg from days 0-5 in the rejection model and from days 0-9 in the long-term functional model. Mean survival time in the rejection model was 98 +/- 2.8 days. Histological examination of these small bowel allografts disclosed signs of chronic rejection. In contrast, all animals of the long-term functional model survived long term (> 250 days) without clinical signs of chronic rejection. The latter model, furthermore, produced evidence of donor-specific tolerance. Whereas heterotopic Dark Agouti (DA) hearts were rejected regularly within 7 days, BN hearts survived indefinitely (> 70 days). In vitro, mixed leukocyte reactivity of CD4+ T cells was similarly strong against donor (BN) antigens as against third-party (DA) antigens. The split tolerance revealed by our in vivo and in vitro results enabled acceptance of both the small bowel allograft without signs of chronic rejection and of donor-specific heart allografts.

Animals↗

Role of muscles accumbens dopamine D1 and D2 receptors in instrumental and Pavlovian paradigms of conditioned reward.

RATIONALE: This study investigated the role of nucleus accumbens dopamine D1 and D2 receptors in two different paradigms of conditioned reward. OBJECTIVE: We addressed the question whether accumbal dopamine is important for the motor or for the motivational components of reward. METHODS: We compared the effects of intra-accumbal infusion of the dopamine D1 receptor antagonist SCH23390 (0.3, 1.0, 3.0 microg) and the D2 receptor antagonist sulpiride (0.3, 1.0, 3.0 microg) on conditioned lever pressing for food, with the effects on the inhibition of the startle response by a conditioned reward signal. RESULTS: Both the D1 and the D2 antagonist dose-dependently attenuated conditioned lever pressing for reward under a fixed-ratio of responding and increased the consumption of freely available lab chow. However, the preference for freely available pellets, and the attenuation of the startle response in the presence of a conditioned stimulus predicting reward were not impaired by blockade of accumbal dopamine receptors. CONCLUSIONS: Our data support the idea that dopamine in the nucleus accumbens is necessary for instrumental response selection in the context of reward rather than for the mere motor performance of behavior or for the evaluation of the hedonic properties of rewarding stimuli.

Animals↗

Kinetic profiles of intraepithelial and invasive prostatic neoplasias: the key role of down-regulated apoptosis in tumor progression.

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly understood. Herein we report the kinetic pattern of PIN, both not associated (primary) and associated (secondary) with coexistent invasive carcinoma (PCa). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeling (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N = (n pi/4)2. Fifty high-power fields (HPF), or the complete lesion if smaller, were screened in each lesion, and both mean and standard deviation were recorded. Statistical differences were studied by means of Fisher's exact test. ISEL indices were significantly (P < 0.0001) lower in PCa (0.1 +/- 0.3) than in primary PIN (0.5 +/- 0.3), while the MIB-I indices were similar in both conditions (P = 0.56). Statistically significant differences were also detected for both MIB-1 and ISEL indices when secondary PIN (MIB-1 1.9 +/- 0.7, ISEL 3.7 +/- 3.3) was compared with primary PIN (MIB-1 2.5 +/- 2.1, ISEL 0.5 +/- 0.3) and PCa (P < 0.0001). In terms of cellularity, primary PIN (26.3 +/- 7.1) revealed scores significantly lower (P < 0.0001) than those recorded in PCa (39.0 +/- 8.8) and secondary PIN (32.9 +/- 14.3). In conclusion, early prostatic tumor is mainly defined by down-regulated apoptosis rather than by increased proliferation. Secondary PIN displays unique kinetic features suggesting an evolved stage of primary PIN.

Aged↗

Vagus-sparing gastric fundectomy in the rat: development of osteopenia, relationship to urinary phosphate and net acid excretion, serum gastrin and vitamin D.

In man and experimental animals, partial and total gastrectomy and gastric vagotomies disturb extracellular mineral homeostasis, osteopenia being among the late outcomes. The sequence of events is complex and insufficiently understood. We report on the long-term effects of gastric fundectomy (FX; FX-1, n=11; sham-operated controls, n=14) sparing gastric vagal fibers at the lesser curvature in the rat, a procedure eliminating gastric acid production but preserving gastric reservoir function. After FX-1 there was a marked increase of gastrinemia [FX-1: 590 (SE 95); controls: 82 (5) pg-equiv/ml; P<0.001], serum 1,25-dihydroxyvitamin D [FX-1: 188 (17); controls: 86 (6) pg/ml; P<0.001], phosphaturia [FX-1: 32 (2); controls 23 (2) micromol/h; P<0.001] due to increased fractional phosphate clearance, elevated urinary net acid [FX-1: 21 (2); controls: 16 (1) micromol/h; P=0.03], and low urinary pH. The urinary excretion of hydroxyproline was increased [FX-1: 137 (15); controls: 99 (8) micromol/h; P=0.01], and crosslinks were also high. These changes were associated with a significant decrease of bone ash calcium, magnesium, and phosphorus. Bone histomorphometry revealed signs of high bone turnover. No signs of hyperparathyroidism were detectable. Acute stimulation of serum gastrin by gastric acid abolishing omeprazole failed to provoke extra-osseous changes, as seen in the long-term after fundectomy. It was concluded that the described type of fundectomy disturbs gastrinemia, acid-base and phosphorus metabolism, thereby initiating osteopenia. This animal model may be suitable for research into post-gastrectomy bone disease.

Acid-Base Equilibrium↗

Amygdaloid N-methyl-D-aspartate and gamma-aminobutyric acid(A) receptors regulate sensorimotor gating in a dopamine-dependent way in rats.

Sensorimotor gating can be measured as prepulse inhibition of the startle response in humans and rats. Since prepulse inhibition is impaired in schizophrenics there is considerable interest in understanding the neuronal basis of prepulse inhibition. Neuropathological findings indicate a dysfunction of the glutamatergic and GABAergic system in cortico-limbic areas in schizophrenics. We tested whether blockade of N-methyl-D-aspartate or GABA(A) receptors in the basolateral amygdala affects prepulse inhibition in rats. Local infusion of the N-methyl-D-aspartate receptor antagonist dizocilpine (0, 6.25 microg/0.5 microl), or of the GABA(A) receptor antagonist picrotoxin (0, 5.0, 10.0 ng/0.5 microl) reduced prepulse inhibition. The prepulse inhibition-disrupting effect of 6.25 microg dizocilpine or 10.0 ng picrotoxin was reversed by systemic co-administration of the dopamine antagonist haloperidol (0.1mg/kg i.p.). These data indicate that sensorimotor gating is regulated in a dopamine-dependent way by N-methyl-D-aspartate and GABA(A) receptors in the basolateral amygdala. Our findings are discussed with respect to neuropathological findings in schizophrenics.

Amygdala↗

Prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury: risk factors for serious complications.

BACKGROUND: 1-2% of all patients under non-steroidal anti-inflammatory drug therapy are exposed to serious upper gastrointestinal complications. The policy of prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal mucosal injury by using misoprostol or suppressing acid secretion is still a matter of debate. AIMS: To discuss the effectiveness of prophylaxis of a gastrointestinal complication during non-steroidal anti-inflammatory drug treatment, according to the number and relevance of risk factors. PATIENTS: A total of 8.843 patients with rheumatoid arthritis, admitted to the widest prospective multicentre mega-trial, on 6-month complication prevention of non-steroidal anti-inflammatory drug-induced ulcers. METHODS: The results are presented in terms of the number of patients to be treated (number needed to treat) in order to prevent one serious upper gastrointestinal complication, and corrected for the number of patients, that receiving the prophylaxis therapy, would lead to one additional withdrawal (number needed to harm). RESULTS: The base-line risk for a complication strongly depended on the number and relevance of risk factors: history of peptic ulcer disease, of gastrointestinal bleeding, of cardiovascular disease, and age. In the general study population, the relative risk reduction of gastrointestinal complications with misoprostol was 40%: thus the number needed to treat to prevent 1 event was 250 in the experimental period (6 months) or 125 when normalized at one-year treatment (1 year number needed to treat]. When considering the prophylaxis gain in intermediate (risk 1-2%) or high risk subjects (patients with a probability of an event over 2%, for the presence of 1 important risk factor or multiple factors), the 1-year number needed to treat rapidly drops from about 100 to about 17. The number needed to harm for one withdrawal was 18. The number needed to treat corrected for withdrawals in order to avoid major complications rises from 125 to 132 in the general population of non-steroidal anti-inflammatory drug users; from 102 to 105 in subjects at intermediate risk, such as patients with history of cardiovascular disease; in the groups at high risk, from 26 to 27 (patients with history of peptic ulcer disease), and from 16 to 17 (patients with history of peptic ulcer disease, cardiovascular disease and aged over 65 years). CONCLUSIONS: Patients at intermediate and high risk for complications from non-steroidal anti-inflammatory drug-induced ulcers should be considered for prophylaxis. In this group of patients, misoprostol prevention of severe complications is effective, and its clinical relevance similar to that of other preventive measures in medical practice.

Adolescent↗

Impairment in a discrimination reversal task after D1 receptor blockade in the pigeon "prefrontal cortex".

Dopamine (DA) is known to modulate cognitive functions of the prefrontal cortex (PFC) of mammals, especially via D1 receptor mechanisms. Like the PFC, the neostriatum caudolaterale (NCL) of birds is characterized by dopaminergic input, and NLC and PFC lesions cause similar deficits. The significance of DA in a color discrimination reversal was assessed by evaluating the effects of bilateral infusions of the D1 receptor antagonist SCH 23390 into the NCL of pigeons (Columba livia). Reversal deficits were qualitatively similar to those in mammals. At a low dose, perseveration occurred predominantly to the incorrect stimulus. Higher doses caused additional spatial perseveration. The data demonstrate, for the first time, that D1 receptor mechanisms in the NCL of pigeons contribute substantially to its function in cognitive processes. Thus, the avian NCL and mammalian PFC could represent functionally equivalent neural networks under control of the DA system.

Animals↗

Upregulation of bradykinin B1-receptor expression after myocardial infarction.

To determine the influence of the myocardial infarction (MI) on bradykinin B1-receptor (B1R) regulation, we studied its expression in the left ventricle (LV) after MI. Rats were submitted to a permanent occlusion of the left coronary artery. Six hours, 24 h and 6 days after MI or after sham operation, left ventricular pressure (LVP) and dP/dt(max) were measured. LV-total RNA was extracted and B1R expression was analysed by a RNase-protection assay (each group n = 6). LVP and dP/dt(max) were impaired at all time points after MI. Basal B1R expression was not detectable in controls. Six hours after MI, the B1R expression was upregulated and reached a maximum 24 h after MI (4 fold vs. 6 h). Six days post-MI, B1R expression returned to levels found 6 h after MI. These data are the first demonstration for an induced myocardial B1R expression in an in vivo model of MI.

Animals↗

Budesonide in the treatment of Crohn's disease: a meta-analysis.

AIM: To perform a meta-analysis to assess the effectiveness and safety of oral budesonide for inducing remission in active Crohn's disease and for preventing relapse in Crohn's disease with medically- or surgically-induced remission. METHODS: All randomized, double-blind controlled trials involving oral budesonide therapy in Crohn's disease were retrieved from a Medline search, reviews articles or their bibliographies. Of 83 articles retrieved, 12 met the inclusion criteria. Data extraction was performed by three independent observers and scoring disagreements were resolved by consensus. RESULTS: Six trials tested budesonide in active disease and six in quiescent disease. Budesonide was less effective than conventional corticosteroids for inducing remission of active Crohn's disease (pooled rate difference, RD -8.5%; 95% CI: -16.4 to -0.7%; P=0.02), but corticosteroid-related adverse events were reduced (RD -22.4%; 95% CI: -32 to -12.8%; P < 0.001). In quiescent Crohn's disease, budesonide was as effective as placebo for preventing relapse in medically induced remission (RD -0.8%; 95% CI: -9.9 to 8.3%; P=0.42) and endoscopic recurrence in surgically induced remission (RD -3.5%; 95% CI: -16.9 to 9.8%; P=0.30). In the long term treatment, budesonide had an occurrence rate of corticosteroid-related adverse effects similar to placebo (RD 5.3%; 95% CI: -3.9 to 14.5%; P=0.30). CONCLUSIONS: Budesonide is significantly less effective than conventional corticosteroids for inducing remission in active Crohn's disease, but the risk of corticosteroid-related adverse effects is significantly reduced. Budesonide is not effective in preventing relapse of Crohn's disease after medically- or surgically-induced remission.

Administration, Oral↗

Comparative genome analysis reveals extensive conservation of genome organisation for Arabidopsis thaliana and Capsella rubella.

Genome colinearity has been studied for two closely related diploid species of the Brassicaceae family, Arabidopsis thaliana and Capsella rubella. Markers mapping to chromosome 4 of A. thaliana were found on two linkage groups in Capsella and colinear segments spanning more than 10 cM were revealed. Detailed analysis of a 60 kbp region in A. thaliana and its counterpart in C. rubella showed virtually complete conservation of gene repertoire, order and orientation. The comparison of orthologous genes revealed very similar exon-intron structures and sequence identities of 90% or more were found for exon sequences. This extensive genome colinearity at the genetic and molecular level allows the efficient transfer of data from the well-studied A. thaliana genome to other species in the Brassicaceae family, substantially facilitating genome analysis studies for species of this family.

Amino Acid Sequence↗

The silent PPARgamma exon 6 CAC(His) --> CAT(His) polymorphism does not affect the plasma leptin levels in a collective of first degree relatives of type 2 diabetes patients from South West Germany.

The peroxisome proliferator activated receptors-gamma (PPARgamma) belong to the superfamily of nuclear transcription factors acting as master genes regulating events in adipocyte differentiation. Thus, PPARgamma is a candidate gene for affecting insulin sensitivity and the pathogenesis of insulin resistance. PPARs trigger endocrine response of two important adipose tissue-derived signalling factors, leptin and tumor necrosis factor-alpha. Leptin is the afferent signal in a negative feedback loop regulating adipose tissue mass and energy balance. It generates insulin-like signals for glucose transport and glycogen synthesis via leptin receptors and the PI3-kinase and could, therefore, play a role as a mediator of obesity-related insulin resistance. Recently, a silent substitution in the coding sequence of the PPARgamma2 gene, leading to the substitution of a C by a T in exon 6 (nt 161), was described. In a recent study, it was proposed that mutations in PPARgamma could play a role in individuals who are at increased risk for developing obesity and type 2 diabetes mellitus by influencing leptin levels. We therefore examined the prevalence of the CAC(His) --> CAT(His) mutation in non-diabetic first degree relatives of subjects with type 2 diabetes to determine a possible association of this mutation to leptin levels and insulin sensitivity. 138 probands were characterised by oral glucose tolerance tests, euglycemic-hyperinsulinemic glucose-clamp and by measuring leptin levels. We found 93 (67.4%) probands without the CAC(His) --> CAT(His) substitution and 45 heterozygotes (36.6%). When the whole group was analysed for an association of the mutation with plasma leptin concentration and insulin sensitivity, no statistical significance could be demonstrated. Independently of the mutation, leptin levels were significantly (p<0.001) higher in female subjects.

Adolescent↗

The PPARgamma2 polymorphism pro12Ala is associated with better insulin sensitivity in the offspring of type 2 diabetic patients.

Recently, a highly prevalent polymorphism of the PPARgamma2-receptor (Pro12Ala) was described and found to be associated with reduced transcriptional activity. Both human and animal studies suggested that this polymorphism may be associated with increased insulin sensitivity. However, an effect independent of other factors known to influence insulin sensitivity has yet to be demonstrated. Therefore, we compared insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique in 37 subjects heterozygous for the PPARgamma2-Pro12Ala mutation and 37 control subjects negative for the PPARgamma2-Pro12Ala. The control group was selected from 190 subjects by pair-matching for sex, BMI, fat distribution and body composition. In the group heterozygous for the polymorphism steady-state plasma insulin during the clamp was significantly lower (63.3 microU/ml +/- 2.8) than in the control group (74.9 microU/ml +/- 4.0, p = 0.02). While MCR of glucose was similar in the PPARgamma2-Pro12Ala group (8.1 ml/kg x min x 100 +/- 0.5) and the control group (7.6 ml/kg x min x 100 +/- 3.0, p = 0.7), the insulin sensitivity index was significantly higher in the PPARgamma2-Pro12Ala group (12.5 mg/kg x min x microU/ml +/- 0.9 vs. 9.7 mg/kg x min x microU/ml +/- 0.8, p = 0.039). In addition, an arbitrary lipolysis index (decrease in FFA divided by increase in insulin) was also found to be marginally higher in the PPARgamma2-Pro12Ala group (8.0 +/- 0.9) compared to the control group (6.1 +/- 0.7, p = 0.097). In conclusion, these data suggest that the PPARgamma2-Pro12Ala mutation is associated with better insulin sensitivity of glucose disposal and possibly, also of antilipolysis.

Adult↗

Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response.

PURPOSE: Photodynamic therapy (PDT), the light activation of photosensitizers to produce free radicals, is known to inhibit experimental intimal hyperplasia (IH). However, its clinical application has been limited by the lack of a suitable approach and a clinically appropriate photosensitizer. The aim of this study was to determine the effectiveness of a clinical approach for PDT, while testing its ability to favorably modulate the vascular wound healing response. METHODS: Rat carotid arteries were balloon-injured (BI), and for PDT, the arteries were irradiated with thermoneutral laser light (lambda = 660 nm, 100 J/cm(2)) after the photosensitizer methylene blue (MB) was delivered locally. Control rats included BI alone and MB after BI alone. Arteries were analyzed after 2 weeks with morphometric evaluation (n = 6) and in situ hybridization for versican and procollagen type I gene expression (digitized image pixel analyses, n = 3). RESULTS: No IH developed in PDT-treated arteries (0 +/- 0 mm(2); compared with BI, 0.192 +/- 0.006 mm(2); P <.0001). The diameters remained unchanged (PDT, 0.95 +/- 0.04 mm; BI, 0.94 +/- 0.05 mm; uninjured artery, 0.91 +/- 0.06 mm). Arterial injury resulted in an increase of versican and procollagen type I messenger RNA (mRNA) in the adventitia and neointima. In the repopulating cells of the adventitia after PDT, there was a significant decrease in versican mRNA (% of positive pixels per high-power field: PDT, 1.13% +/- 0.39%; BI, 2.93% +/- 0.61%; P <.02), but not in procollagen type I mRNA. CONCLUSION: The decrease of versican mRNA expression of repopulating cells after PDT reflects favorable healing on a molecular level. Site-specific delivery of MB, a clinically appropriate photosensitizer, followed by PDT represents a suitable method to promote favorable healing after balloon intervention and further supports its role for inhibiting postinterventional restenosis.

Analysis of Variance↗

An assessment of eddy current sensitivity and correction in single-shot diffusion-weighted imaging.

Artefacts caused by eddy currents are a major problem in diffusion weighted imaging. This is particularly acute in experiments in which a number of images with differing degrees of diffusion weighting and/or differently oriented diffusion-weighting gradients need to be combined. The echo-planar imaging sequence is particularly sensitive to the effects of residual eddy currents, especially due to the low bandwidth in the phase-encoding direction. Two published schemes are investigated regarding the effectiveness of eddy current correction. That of Jezzard et al (1998 Magn. Reson. Med. 39 801-12) requires the acquisition of additional experimental data in order to perform a post-acquisition correction, whereas that of Wider et al (1994 J. Magn. Reson. A 108 255-8) attempts to reduce the eddy currents directly. It is found that the latter experiment gives a somewhat superior performance and a combination of the two approaches results in an almost complete elimination of artefact. An alternative single-shot imaging experiment to echo-planar imaging is given by sequences based on fast spin-echo methods, which should be insensitive to the effects of constant eddy currents. It is shown that the intrinsic eddy-current-related artefact level in such experiments is indeed low, residual artefacts being attributed to eddy current decay during the echo train. In situations of poor main magnetic field homogeneity or large eddy currents such sequences may be gainfully used instead of echo-planar imaging.

Diagnostic Imaging↗

Detection of hematogenic tumor cell dissemination in patients undergoing resection of liver metastases of colorectal cancer.

OBJECTIVE: To determine the extent of pre- and intraoperative hematogenic tumor cell dissemination in patients undergoing liver resection for metastatic colorectal cancer. SUMMARY BACKGROUND DATA: For patients with hepatic metastases of colorectal cancer, liver resection is the only potentially curative therapy. However, 38% to 53% of patients develop extrahepatic tumor recurrence, probably caused by tumor cells disseminated before or during surgery not detected by current staging systems. METHODS: Blood samples harvested before, during, and after surgery from 41 patients and bone marrow samples from 30 patients undergoing resection of liver metastases of colorectal cancer were analyzed for disseminated tumor cells using cytokeratin 20 reverse transcriptase-polymerase chain reaction. RESULTS: Tumor cells were detected in the blood samples of 26 of the 41 patients (63.4%) and in the bone marrow samples of 8 of the 30 patients (26.7%). Tumor cells were detected significantly more often during surgery than before or after surgery. Intraoperative tumor cell dissemination was detected in 41.7% of patients undergoing resection of two or more liver segments but only 14.3% of patients undergoing resection of one liver segment. Compared with resection of primary colorectal cancer, major liver resection carries an increased risk for intraoperative tumor cell dissemination. CONCLUSIONS: Detection of disseminated tumor cells in patients undergoing liver resection for metastases of colorectal cancer using cytokeratin 20 reverse transcriptase-polymerase chain reaction might help to identify patients at high risk for tumor recurrence who may benefit from adjuvant therapy. Major liver resection of metastases leads to frequent intraoperative tumor cell shedding, possibly preventable by alternative surgical strategies.

Adult↗