Search PubMed⌕ Search

Biomedical subjects

C Fenger

Publications and source records attributed to C Fenger.

At least 37 records · Page 2Linked to original sources
PubMed1999

The expression of p53, Ki-67 and urokinase plasminogen activator receptor in colorectal adenomas with true invasion and pseudoinvasion.

The recognition of pseudoinvasion is important in the differential diagnosis of adenocarcinoma in patients with adenomas. This distinction might occasionally be difficult, particularly when the dysplasia is pronounced. The present study was undertaken in order to investigate whether the immunohistochemical expression of p53, Ki-67 and the urokinase plasminogen activator receptor (uPAR) was different in adenomas with true invasion and pseudoinvasion. We studied 26 formalin-fixed, paraffin-embedded tumor samples, consisting of 10 cases of adenomas with pseudoinvasion and 16 cases of adenocarcinomas in adenomas. In this series of selected histologically typical cases a constant moderate or strong reaction for uPAR was present at the invasive front in all of the 16 adenomas with adenocarcinoma, but only focally in one of 10 adenomas with pseudoinvasion. The reactions for p53 and Ki-67 showed only minor differences. In conclusion, the immunohistochemical reaction for uPAR seems to be a useful supplement in cases without typical histology or with severe dysplasia.

Adenocarcinoma↗
PubMed1999

Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair.

BACKGROUND: Despite intensive research into the molecular abnormalities associated with colorectal cancer (CRC), no diagnostic tests have emerged which usefully complement standard histopathological assessments. AIMS: To assess the feasibility of using immunohistochemistry to detect replication error (RER) positive CRCs and determine the incidence of RER positivity within distinct patient subgroups. METHODS: 502 CRCs were analysed for RER positivity (at least two markers affected) and/or expression of hMSH2 and hMLH1. RESULTS: There were 15/30 (50%) patients with metachronous CRCs, 16/51 (31%) with synchronous CRCs, 14/45 (31%) with a proximal colon carcinoma, and 4/23 (17%) who developed a CRC under the age of 50 showed RER positivity. However, 0/54 patients who developed a solitary carcinoma of the rectum/left colon over the age of 50 showed RER positivity. Immunohistochemical analysis revealed that 66/66 (100%) RER positive carcinomas were associated with complete lack of expression of either hMSH2 or hMLH1. This correlation was confirmed using a further 101 proximal colon carcinomas. Patients with a mismatch repair defective carcinoma showed improved survival but a 5.54 times relative risk of developing a metachronous CRC. A prospective immunohistochemical study revealed 13/117 (11%) patients had a mismatch repair defective carcinoma. A fivefold excess of hMLH1 defective cases was noted. CONCLUSIONS: All RER positive carcinomas were identified by the immunohistochemical test. This is the first simple laboratory test which can be performed routinely on all CRCs. It will provide a method for selecting patients who should be investigated for HNPCC, offered long term follow up, and who may not respond to standard chemotherapy regimens.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Clinical evidence for the adenoma-carcinoma sequence.

A review is given on evidence supporting or rejecting the hypothesis of a colorectal adenoma-carcinoma sequence. The majority of studies discuss adenomas from a clinical point of view, but pathology has also been considered in detail, and molecular biology has been touched on. It is concluded the adenoma stage is, most probably, a phase on the way to carcinoma. But it remains to be shown what effect the removal of adenomas will have in the long run on the incidence of colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

Cytogenetic analysis of colorectal adenomas: karyotypic comparisons of synchronous tumors.

The phenotypic progression of colorectal tumors is driven by their step-by-step acquisition of genomic alterations. These pathogenetically important mutations are at the same time markers of tumor clonality. The aim of this study was to describe the clonal relation among synchronous colorectal adenomas. Twenty-four colorectal adenomas from 11 patients were subjected to chromosome banding analysis. Clonal chromosome abnormalities were found in 20 tumors. Recurrent structural rearrangements involved chromosomes 1, 13, 17, and 18. The most common numerical changes were gain of chromosomes 7, 13, 20, and 3 and loss of chromosome 18. Eight adenomas had subclones as evidence of clonal evolution. Similar clones in separate polyps were seen in tumors from 6 patients; these adenomas were always located in the same part of the large bowel. In 2 patients, both with one rectal adenoma and one adenoma in the colon, no karyotypic similarity between the lesions was found. Our findings indicate that whereas close, but macroscopically distinct, synchronous colorectal adenomas usually have a common pathway of progression, perhaps even the same clonal origin, large bowel adenomas at a considerable distance from one another exhibit karyotypic differences, indicating that they arise independently.

Adenoma↗
PubMed1998

Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers.

Our purpose was to clarify whether human colorectal cancer cells are equipped to present tumour-associated-antigens to the immune system, and whether this ability correlates with lymphoid infiltration, the Dukes' stage and Jass classification. Enzymatically dissociated tumour cells from 70 different colorectal cancers were monitored by multiparameter flow cytometry. Gating on EP4+ cells, the expression of the surface molecules HLA class I, HLA class II, CD80 (B7-1), CD54 (ICAM-I) and CD58 (LFA-3) was evaluated. In 60 of 70 tumours, all tumour cells expressed HLA class I, in 10 tumours 15-96% of the tumour cells expressed HLA class I. In 1 tumour, all tumour cells expressed HLA class II, in 67 tumours some expressed HLA class II, in 2 tumours none expressed HLA class II. Expression of CD58 was heterogeneous, and there was no or only sparse expression of CD80 and CD54. Expression of the HLA class I molecules, but not the class II, was correlated with lymphoid infiltration and the Jass classification. Expression of these surface molecules was not correlated with the Dukes' stage. The tumour cells were generally equipped to present antigens to the effector arm of the immune system since HLA class I is expressed, but the tumour cells were not optimal in stimulating an immune response, since HLA class II and CD58 were only marginally expressed and CD80 and CD54 were absent.

Adult↗
PubMed1998

Allelic imbalance and cytogenetic deletion of 1p in colorectal adenomas: a target region identified between DIS199 and DIS234.

Both cytogenetic and molecular genetic analyses have shown that many colorectal adenomas carry an acquired deletion distally in the short arm of one chromosome 1, but the two methods have never been brought to bear on the same tumors. The major part of this study was the analysis of 53 previously short-term cultured and karyotyped colorectal adenomas for allelic imbalance at eight microsatellite loci in 1p. Allelic imbalances were detected in seven of the 12 adenomas that had cytogenetically visible abnormalities of chromosome 1, as well as in four adenomas that either had a normal karyotype (one case) or had clonal chromosome abnormalities that did not seem to involve chromosome 1 (three cases); i.e., 30% of the adenomas had abnormalities involving 1p by the combined approach. A minimal region of overlap seemed to map to between DIS199 and DIS234, suggesting that this is a relevant target region. This genomic area contains the human homologue of the tumor modifier gene Mom1 (1p35-36.1), which, in mice, modifies the number of intestinal tumors in multiple intestinal neoplasia (Min)-mutated animals. To evaluate whether the imbalances corresponded to interstitial deletions of 1p material, we performed fluorescence in situ hybridization with a pericentromeric probe (15 adenomas) and a telomeric probe (6 adenomas) on uncultured cells from the 16 adenomas with chromosome 1 abnormalities. Except for three adenomas that had already been shown by banding analysis to have a trisomic pattern, two centromere 1 signals were invariably found. In the cases hybridized with the 1p-telomeric probe, we found the same frequencies of telomeric and centromeric signals, in agreement with the interpretation that the deletions were interstitial. One of the 53 adenomas had genomic instability, seen as new alleles at five of eight microsatellite loci. A comparison of the genetic findings with clinicopathologic data indicated that adenomas in the rectum have 1p abnormalities more often than do adenomas of the sigmoid colon, and that adenomas with 1p changes are larger than adenomas without abnormalities of chromosome 1.

Adenoma↗
PubMed1998

A comparison of flow cytometry and immunohistochemistry in human colorectal cancers.

In human colorectal cancer it has been reported that some tumours lack the HLA-ABC antigens. This has been interpreted as reflecting tumour escape from the immune system. Earlier data have been obtained by immunohistochemistry. In this study, we compared the expression of HLA-ABC, HLA-DR, CD80 (B7-1) and CD54 (ICAM-1) in 20 tumours using both a conventional immunohistochemistry two-layer technique and multiparameter flow cytometry, gating on an epithelial cell marker. Colorectal cancer tissue used in flow cytometry was dissociated with collagenase, deoxyribonuclease and hyaluronidase. The intensity of expression of HLA-ABC, HLA-DR and CD80 was unaffected by the enzymes, but CD54 was decreased by 30%. The reproducibility of flow cytometry was good. Microscopy of sections revealed that about 5% of each tumour sample consisted of normal epithelium, but even after correction for this, flow cytometry was superior to immunohistochemistry in 33 out of 80 cases, and showed that tumours described as HLA-ABC negative by immunohistochemistry were in fact weakly positive for HLA-ABC. We conclude that flow cytometry and immunohistochemistry are complementary, and that flow cytometry is superior to immunohistochemistry for detecting antigens/epitopes present in low amounts.

Aged↗
PubMed1997

[Randomized population study of screening for intestinal cancer with Hemoccult-II].

The aim of the randomised study was to compare mortality rates from colorectal cancer (CRC) in persons screened with faecal occult-blood tests every two years during a 10-year period with those of unscreened similar controls. Thirty thousand nine hundred and sixty-seven persons aged 45-75 years in 1985 were allocated to screening and another 30,966 to a control group. Only participants who completed the first round with Hemoccult-II were invited for further screening. Participants with positive tests were offered colonoscopy. The primary endpoint was death from CRC. Sixty-seven percent completed the first screening round, and of these more than 90% accepted repeated screenings. During the 10 year study, 481 persons in the screening group had a diagnosis of CRC, compared with 483 unscreened controls. CRC mortality was significantly lower in the screening group (205 deaths) than in controls (249 deaths) (mortality ratio 0.82 [95% conf. lim. 0.68-0.99], p = 0.03). Our findings indicate that biennial screening by faecal occult-blood tests can reduce CRC mortality.

Adenoma↗
PubMed1997

Cytogenetic findings in metastases from colorectal cancer.

Eighteen tumor samples from 11 patients with metastatic colorectal cancer were cytogenetically analyzed after short-term culturing. Of the 13 metastases examined, 11 were from lymph nodes, 1 from the peritoneum and 1 from the lung. In 5 of the 11 patients, matched samples from the primary tumor and lymph node metastases were analyzed. Cytogenetic similarities between the primary and secondary lesions were found in all 5 cases, indicating that many of the chromosomal aberrations presumably occurred before disease spreading took place. Compared with the primaries, the metastases appeared to exhibit decreased clonal heterogeneity but, concurrently, an increase in the karyotypic complexity of individual clones. Among the aberrations recurrently found in metastatic lesions were del(1)(p34), i(17)(q10), -18, -Y, -21, +7 and +20, all of which have been seen repeatedly in previous series of primary colorectal carcinomas, and del(10)(q22) and add(16)(p13), which so far have not been associated with primary tumors and which may play a particular pathogenetic role in the metastatic process.

Adenocarcinoma↗
PubMed1997

[Reversible liver steatosis in patients treated with 5-fluorouracil and interferon-alpha].

Twenty-three patients with metastatic colorectal carcinoma were randomized as part of two multicenter Phase III trials to receive either 5-fluorouracil (5-FU)/interferon alpha-2A (INF-alpha) or 5-FU +/- leucovorin. The patients were evaluated regularly for response by CT of the abdomen when treatment began and then every six to eight weeks. incidentally, we found that four of 13 patients treated with 5-FU/INF-alpha and none of ten patients treated with 5-FU +/- leucovorin developed hepatic steatosis during treatment. The diagnoses were based on a decreased CT value of the liver parenchyma by the repeated CT, and histologically verified by liver biopsies. There was no relationship to cumulative 5-FU or INF-alpha dose. Based on posttreatment CT, the liver parenchyma changes were reversible after therapy was stopped. Recognition of this condition in patients receiving 5FU/INF-alpha is important to prevent a patient from being labeled as having progressive hepatic metastases.

Antimetabolites, Antineoplastic↗
PubMed1997

The pattern of recurrent colorectal cancer in a prospective randomised study and the characteristics of diagnostic tests.

In a prospective randomised study, 597 patients subjected to curative surgery for colorectal cancer were allocated to either a group with frequent follow-up or a control group with follow-up every 5 years. The pattern of recurrence is reviewed. An equal number of recurrences was detected in the two groups, but the recurrence was diagnosed 9 months earlier in patients followed frequently, and the diagnostic characteristics of various tests dependent upon how often they were used. It is unlikely that frequent follow-up after curative surgery for colorectal cancer has a large positive influence upon survival, but a small benefit from an intensive follow-up program cannot be ruled out. The present results indicate that clinical examination, digital rectal examination, proctoscopy, colonoscopy and chest x-ray should be included in such a programme, whereas others (blood haemoglobin, faecal occult blood test, double contrast braium enema, serum alanine aminotransferase, and serum bilirubin) should be avoided, having a low sensitivity for detecting recurrent colorectal cancer.

Adult↗
PubMed1997

Amantadine and equine influenza: pharmacology, pharmacokinetics and neurological effects in the horse.

Amantadine is an antiviral agent effective against influenza A viruses. We investigated 1) the antiviral efficacy, 2) analytical detection, 3) bioavailability and disposition, 4) pharmacokinetic modelling and 5) adverse reactions of amantadine in the horse. In vitro, amantadine and its derivative rimantadine suppressed the replication of recent isolates of equine-2 influenza virus with effective doses (EDs) of less than 30 ng/ml. Rimantadine was more effective than amantadine against most viral isolates; we suggest a minimum plasma concentration of 300 ng/ml of amantadine for therapeutic efficacy. In vivo an i.v. dose of amantadine 15 mg/kg bwt produced mild, transient CNS signs which were no longer apparent after 30 min. Amantadine administered at a dose of 15 mg/kg bwt was established as the maximum safe single i.v. dose. However, if repeated i.v. administration of amantadine is required no more than 10 mg/kg bwt t.i.d. should be used. The maximal safe plasma concentration of amantadine was not evaluated but is probably greater than 2000 ng/ml and possibly greater than 4000 ng/ml. On the other hand, horses with lower seizure thresholds, or those on medications that lower seizure thresholds, may be at increased risk of amantadine-induced seizures, which show few premonitory signs and are rapidly fatal. After i.v. administration of amantadine 10 mg/kg bwt, the disposition kinetics were well fitted by a 2-compartment open model. The estimated peak plasma concentration after this dose was about 4500 ng/ml, the volume of distribution at steady-state (Vdss) was (mean +/- s.d.) 4.9 +/- 1.9 l/kg bwt and the beta phase half-life was 1.83 +/- 0.87 h. Computer projections of plasma amantadine concentrations after i.v. administration of amantadine at a dose of 10 mg/kg bwt t.i.d. at 8 h intervals suggest peak plasma concentrations of 4000-5000 ng/ml and troughs of less than 300 ng/ml will be achieved. Amantadine administered orally at 10 mg/kg bwt and 20 mg/kg bwt showed mean oral bioavailability of about 40-60% and a plasma half life of 3.4 +/- 1.4 h; however, there was substantial inter-animal variation in bioavailability. Projections based on the kinetics observed in individual animals suggest that some animals readily maintain effective plasma concentrations of amantadine after oral administration of 20 mg/kg bwt t.i.d. On the other hand, animals in which amantadine is poorly bioavailable may require up to a 6-fold (120 mg/kg bwt) increase in the oral dose to achieve effective blood concentrations. Withholding food for 15 h did not reduce these inter-animal differences in bioavailability. Our results showed that simple dosing with oral amantadine will not yield effective plasma concentrations in all animals. While i.v. administration yielded more reproducible plasma concentrations, care should be taken to see that the seizure threshold is not exceeded. In acute situations, i.v. administration (5 mg/kg bwt) every 4 h should maintain safe and effective plasma and respiratory tract concentrations of amantadine.

Administration, Oral↗
PubMed1997

A prospective randomized study of follow-up after radical surgery for colorectal cancer.

BACKGROUND: The possible benefit for patients from follow-up examinations after curative surgery for colorectal cancer is unproven. The purpose of this study was to determine whether survival is improved by frequent follow-up examinations. METHODS: A total of 597 patients less than 76 years old treated with radical surgery for colorectal cancer were included in the study from 1983 to 1994. Patients were randomized to frequent follow-up (group 1) or virtually no follow-up (group 2) with examinations at 5 and 10 years. RESULTS: Group 1 comprised 290 patients, group 2 contained 307. Recurrence was equally frequent (26 per cent), but the time of diagnosis was 9 months earlier in group 1; also, more recurrences were asymptomatic in group 1 and more patients had new surgery with curative intent (P = 0.02). However, no improvement in overall survival or in cancer-related survival resulted. CONCLUSION: Patients subjected to intensive follow-up have recurrence diagnosed earlier, and have more operations for recurrence, but the survival results suggest that any major improvement by intensive follow-up is unlikely.

Adult↗
PubMed1996

Randomised study of screening for colorectal cancer with faecal-occult-blood test.

BACKGROUND: Case-control studies and a voluntary-based follow-up study have suggested that repeated screening with faecal-occult-blood (FOB) tests can lead to a reduction in mortality from colorectal cancer (CRC). The aim of this randomised study was to compare mortality rates after FOB tests every 2 years during a 10-year period with those of unscreened similar controls. METHODS: 140,000 people aged 45-75 years lived in Funen, Denmark, in August, 1985, and were considered for inclusion in our study. Before randomisation we excluded individuals who had CRC or precursor adenomas and those who had taken part in a previous pilot study. Randomisation of 137,485 people in blocks of 14 allocated three per 14 to the screening group (30,967), three per 14 to the control group (30,966), and eight not to be enrolled in the study (75,552). Controls were not told about the study and continued to use health-care facilities as normal. Hemoccult-II blood tests (with dietary restrictions but without rehydration) were sent to screening-group participants. Only those participants who completed the first screening round were invited for further screening--five rounds of screening during a 10-year period. Participants with positive tests were asked to attend to full examination and were offered colonoscopy whenever possible. The primary endpoint was death from CRC. FINDINGS: Of the 30,967 screening-group participants, 20,672 (67%) completed the first screening round and were invited for further screening; more than 90% accepted repeated screenings. During the 10-year study, 481 people in the screening group had a diagnosis of CRC, compared with 483 unscreened controls. There were 205 deaths attributable to CRC in the screening group, compared with 249 deaths in controls. CRC mortality, including deaths attributable to complications from CRC treatment, was significantly lower in the screening group than in controls (mortality ratio 0.82 [95% CI 0.68-0.99]) p = 0.03). INTERPRETATION: Our findings indicate that biennial screening by FOB tests can reduce CRC mortality. This study is being continued to improve its statistical power and to assess the effect of the removal of more precursor adenomas in the screening-group participants than in controls on CRC incidence.

Adenoma↗
PubMed1996

[Intraoperative ultrasonography in colorectal cancer. A prospective, blind study].

This study was designed to compare diagnostic accuracies of measuring liver enzymes, preoperative ultrasonography, surgical examination, and intraoperative ultrasonography for detection of liver metastases from colorectal cancer. A blind prospective comparison between the diagnostic examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations and the results were not known to the other experienced ultrasonologist, who did the intraoperative examinations. The latter was also unaware of the findings by the surgeon. The presence of metastases was further assessed by ultrasonography three months postoperatively, as well as surgery and liver biopsy in some of the patients. The sensitivity of intraoperative ultrasonography (62/64) was significantly superior to that of surgical exploration (54/64), and that of preoperative ultrasonography (45/64). The lowest sensitivity was presented by liver enzymes. "Bilobar" metastases were detected in 42 of 46 patients by intraoperative ultrasonography, but in no more than 33 by the surgeon. Intraoperative ultrasonography demonstrated the highest specificity of all examinations. Intraoperative ultrasonography reduces the number of patients with liver metastases being subjected to superfluous or even harmful liver surgery and it may increase the number in whom liver surgery will prolong life.

Adult↗
PubMed1996

Comparison of two techniques of transrectal ultrasonography for the assessment of local extent of polypoid tumours of the rectum.

The capability of transrectal ultrasonography (TRUS) to differentiate between benign and malignant rectal polyps was evaluated. Digital palpation and sigmoidoscopy were followed by TRUS with a 7.5-MHz linear-array transducer, in a blinded design. In the second part of the study the procedure was extended with an acoustic window system (AWS), preventing compression of the polyp. Pathological examination after surgical resection was used for definitive diagnosis in 110 polyps. Digital examination detected 10 of 22 carcinomas with adenomas, compared with 19 by TRUS (P < 0.01). However, TRUS falsely indicated 20 of 49 adenomas to be carcinomas, compared with 4 out of 49 by digital examination (P < 0.001). TRUS combined with AWS detected 23 of 24 carcinomas, and gave a false positive result in only 3 of 26 benign polyps. The results suggest that the best way to discriminate between benign and malignant rectal polyps is to combine TRUS with AWS.

Adult↗
PubMed1996

Chromosome abnormalities in colorectal adenomas: two cytogenetic subgroups characterized by deletion of 1p and numerical aberrations.

Cytogenetic analysis of short-term cultures from 34 benign colorectal polyps, all histologically verified as adenomas, revealed clonal chromosome aberrations in 21 of them. Eight polyps had structural rearrangements, whereas only numerical changes were found in 13. A combination of structural and numerical chromosomal aberrations was found in three polyps. The most common numerical change was gain of chromosome 7, found either as the sole anomaly (five polyps), together with other numerical changes (six polyps), or together with structural rearrangements (two polyps). Other recurrent numerical changes were +20, +13, and monosomy 18, found in six, five, and two adenomas, respectively. Rearrangement of chromosome 1 was the most common structural change. Abnormalities involving 1p were seen in six adenomas, leading to visible loss of material in three. One adenoma had one clone with a large and another with a small 1p deletion. In three adenomas, del(1)(p36) was the only cytogenetic aberration, supporting the authors' previous conclusion that loss of one or more gene loci in band 1p36 is a common early change in colorectal tumorigenesis. Chromosome 8 was involved in structural changes in two adenomas; in one this led to loss of 8p and in the other to gain of 8q. The cytogenetic findings did not correlate in a statistically significant manner with clinicopathologic parameters, such as grade of dysplasia, macroscopic or microscopic adenoma structure, tumor size and location, or the patients' sex and age.

Adenoma↗