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Biomedical subjects

C Fenger

Publications and source records attributed to C Fenger.

At least 55 records · Page 3Linked to original sources
PubMed1995

Reversible hepatic steatosis in patients treated with interferon alfa-2a and 5-fluorouracil.

BACKGROUND: Thirty previously untreated patients with metastatic colorectal carcinoma were randomized as part of two multicenter Phase III trials. Twenty-two patients were randomized to receive either 5-fluorouracil (5-FU)/interferon alfa-2A (IFN-alpha) or 5-FU/leucovorin (11 patients in each arm). Eight patients were randomized to receive 5-FU/IFN-alpha or 5-FU alone (4 patients in each arm). METHODS: Twenty-three patients (13 patients treated with 5-FU/IFN-alpha and 10 patients treated with 5-FU/leucovorin or 5-FU alone) were evaluated regularly for response by computed tomography (CT) scans of the abdomen when treatment began and then every 6-8 weeks. RESULTS: Incidentally, four patients developed hepatic steatosis during treatment with IFN-alpha and 5-FU. The diagnosis was based on a decreased CT value of the liver parenchyma by repeated CT scans of the abdomen during treatment, and this diagnosis was verified histologically by liver biopsy. There was no relationship to cumulative IFN-alpha or 5-FU dose. Based on posttreatment CT scans, the liver parenchyma changes were reversible after therapy was stopped, and there were no significant clinical sequelae. No patients treated with 5-FU/leucovorin or 5-FU alone experienced a decreased CT value of the liver parenchyma. CONCLUSION: Hepatic steatosis was been observed in approximately 30% of patients treated with IFN-alpha and 5-FU. The hepatic changes were fully reversible after the treatment was stopped. Recognition of this condition is important to prevent a patient from being labeled as having progressive hepatic metastases.

Adenocarcinoma↗
PubMed1995

[Rectal exploration and transrectal ultrasound scanning of rectal cancer. A prospective, blind study].

Staging of rectal carcinoma before surgical treatment was performed in a prospective blind study, comparing digital rectal exploration and transrectal linear ultrasonography (TRUS) with the resulting pathological examination. TRUS underestimated the depth of penetration in three of 33 patients and overestimated it in nine of 74. The figures for digital examination were five of 18 and 20 of 76, respectively. Penetration of the rectal wall was correctly identified in 56 of 61 patients by digital rectal examination and in 59 of 61 by TRUS. Specimens without penetration of the rectal wall were identified in 26 of 33 patients by TRUS, but in no more than 13 of 33 by digital examination. Regional lymph node metastases were present in 19 patients; none were diagnosed by digital examination, but TRUS identified 11 of the 19. It is concluded that TRUS will result in more patients being given the possibility of curative local surgery.

Double-Blind Method↗
PubMed1995

Karyotypic characterization of colorectal adenocarcinomas.

Cytogenetic analysis of short-term cultures from 52 primary colorectal adenocarcinomas revealed clonal chromosome aberrations in 45 tumors, whereas the remaining 7 had a normal karyotype. More than 1 abnormal clone was detected in 26 tumors; in 18 of them, the clones were cytogenetically unrelated. The modal chromosome number was near-diploid in 32 tumors and near-triploid to near-tetraploid in 13. Only numerical aberrations were identified in 13 carcinomas, only structural aberrations in 3, and 29 had both numerical and structural changes. The most common numerical abnormalities were, in order of decreasing frequency, gains of chromosomes 7, 13, 20, and Y and losses of chromosomes 18, Y, 14, and 15. The structural changes most often affected chromosomes 1, 17, 8, 7, and 13. The most frequently rearranged chromosome bands were, in order of decreasing frequency, 13q10, 17p10, 1p22, 8q10, 17p11, 7q11, 1p33, 7p22, 7q32, 12q24, 16p13, and 19p13. Frequently recurring aberrations affecting these bands were del(1)(p22), i(8)(q10), i(13)(q10), and add(17)(p11-13). The most common partial gains were from chromosome arms 8q, 13q, and 17q and the most common partial losses from chromosome arms 1p, 8p, 13p, and 17p. A correlation analysis between the karyotype and the clinicopathologic features in our total material, which consists of altogether 153 colorectal carcinomas, including 116 with an abnormal karyotype, showed a statistically significant association (P < 0.05) between the karyotype and tumor grade and site. Carcinomas with structural chromosome rearrangements were often poorly differentiated; well and moderately differentiated tumors often had only numerical aberrations or normal karyotypes. Abnormal karyotypes were more common in rectal carcinomas than in carcinomas situated higher up. Near-triploid to near-tetraploid karyotypes were more than twice as frequent in tumors of the distal colon as in those of the proximal colon and rectum. The cytogenetic data indicate that carcinomas located in the proximal colon and rectum, which often are near-diploid with simple numerical changes and cytogenetically unrelated clones, probably arise through different mechanisms than do tumors located in the distal colon, which more often have complex near-triploid to near-tetraploid karyotypes.

Adenocarcinoma↗
PubMed1995

Intraoperative ultrasonography in detection of hepatic metastases from colorectal cancer.

PURPOSE: 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. METHODS: Blind, prospective comparisons of diagnostic examinations mentioned above were performed in 295 consecutive patients with colorectal cancer. An experienced ultrasonologist performed the preoperative examinations, and results were unknown to the other experienced ultrasonologist who performed the intraoperative examinations. The latter, also was unaware of the findings by the surgeon. The presence of metastases was further assessed by ultrasonography three months postoperatively, as well as additional surgery and liver biopsy in some of the patients. RESULTS: 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 only 33 patients by the surgeon. Intraoperative ultrasonography demonstrated the highest specificity of all examinations. CONCLUSIONS: Intraoperative ultrasonography reduces the number of patients with liver metastases from being subjected to superfluous or even harmful liver surgery, and it may increase the number in whom liver surgery will prolong life.

Adult↗
PubMed1995

Booster vaccination against diphtheria and tetanus in man. Comparison of calcium phosphate and aluminium hydroxide as adjuvants--II.

Diphtheria and tetanus antibody levels were measured before and four weeks after booster vaccination of 313 Danish military recruits participating in a clinical trial to compare aluminium hydroxide and calcium phosphate as adjuvants in diphtheria-tetanus vaccines (DT). Twenty-eight percent of the men had a diphtheria pre-vaccination content below a protective level of 0.01 IU ml-1. The calcium phosphate adsorbed vaccine showed the highest efficacy for both antigens. Adverse reactions were rare but more frequent in the calcium group than in the aluminium group. No correlation was found between pre- or post-vaccination levels and adverse reactions and both vaccines gave rise to specific IgE formation. The results show that calcium phosphate is more effective but not a safer alternative to aluminium hydroxide when compared in vaccines containing 1.0 mg ml-1 of Ca or of Al.

Adjuvants, Immunologic↗
PubMed1995

A randomized surveillance study of patients with pedunculated and small sessile tubular and tubulovillous adenomas. The Funen Adenoma Follow-up Study.

BACKGROUND: We wanted to assess the influence of various surveillance intervals on the risk of new neoplasia after removal of pedunculated and small sessile tubular and tubulovillous adenomas. METHODS: After initial colonoscopic polypectomy patients were randomized to surveillance with either 2 years (group A) or 4 years (group B) between colorectal examinations. RESULTS: The cumulated risk of a patient having new adenomas was 35.0% (28.7-41.4%) in group A and 35.5% (28.4-42.7%) in group B after 48 months. The risk increased to 44.9% (36.0-53.9%) and 60.1% (48.5-71.7%), respectively, after 96 months. The risk of significant neoplasia (carcinoma or adenoma with villous structure, severe dysplasia, or diameter > 10 mm) was 5.2% (2.3-8.1%) and 8.6% (3.8-13.3%) after 48 months and 8.6% (4.2-13.0%) and 17.4% (7.6-27.2%) after 96 months. More than one adenoma at first examination was associated with higher risk of new adenomas. Furthermore, we found a tendency for age above 60 years and male gender to be associated with higher risk of new adenomas. More than two adenomas at first examination was the only factor found to be associated with a higher risk of new significant neoplasia. One patient in group A and two patients in group B developed cancer, which is not significantly different from the number expected (3.43) in the average Danish population (RR = 0.9, 0.2-2.6). CONCLUSION: After colonoscopy with removal of all polyps, colorectal examination at 4 years resulted in a similar risk of new adenomas compared with examinations at 2 and 4 years. However, new significant neoplasia tended to be more frequent when first surveillance was at 4 years. Extending the surveillance to 8 years also tended to increase the risk more in the group being examined every 4 years, but reduction of the number of surveillance examinations by more than 50% and a probable reduction of complications from surveillance examinations themselves may justify a recommendation for the longest interval.

Adenoma↗
PubMed1995

Omeprazole in the long-term treatment of gastro-oesophageal reflux disease. A double-blind randomized dose-finding study.

BACKGROUND: Omeprazole is effective in the treatment of reflux oesophagitis, and it is important to determine the lower dose limit with still appropriate clinical efficacy. METHODS: Patients with endoscopic oesophagitis grade 1-4 (N = 220) were randomized to double-blind treatment with 20 mg or 40 mg omeprazole daily for 4-8 weeks. Those healed after this initial treatment phase were re-randomized to double-blind treatment with 20 mg omeprazole daily (n = 67), 10 mg omeprazole daily (n = 68), or placebo (n = 33) for 6 months. Remission was defined as the absence of any endoscopic sign of oesophagitis. RESULTS: Healing rates were increased with 40 mg omeprazole, the therapeutic gain compared with the 20-mg dose being 15% after 4 and 8 weeks. The proportion of patients in remission after 6 months was 59% with 20 mg omeprazole, 35% with 10 mg omeprazole, and 0% with placebo. CONCLUSION: Maintenance treatment with 10 mg omeprazole can prevent recurrence of oesophagitis in about one-third of patients with all grades of oesophagitis, and 20 mg omeprazole in about twice as many.

Adult↗
PubMed1994

[Rectoscopy and Hemoccult-II as initial diagnosis. A procedure in patients with symptoms of irritable colon].

The diagnostic accuracy for colorectal cancer (CRC) of rigid sigmoidoscopy and faecal occult blood test (Hemoccult-II) (H-II) was investigated in patients with irritable bowel syndrome in general practice in a three year period and the results were compared with those of the previous three years, where rigid sigmoidoscopy and double contrast barium enema (DCBE) were the initial preferred examinations. Colonoscopy was recommended in patients with positive H-II, but also in patients with repeated negative H-II within three months, provided that the symptoms persisted. CRC was detected in 141 of 630 patients with positive H-II and in 52 of 8697 with negative H-II. The number of CRC's in the two study periods was similar, in spite of a pronounced reduction in DCBE's from 12,196 to 5656 and a small increase in colonoscopies from 3053 to 4127. It was concluded that the new strategy was no worse than the previous one and the major savings in DCBE's could be used to exchange the rigid sigmoidoscopy with a 60 cm flexible sigmoidoscopy, increasing diagnostic accuracy, shortening delay of diagnosis and removing more adenomas, which eventually may reduce the future incidence of CRC and thereby the mortality from CRC.

Adenoma↗
PubMed1994

[99mTc anti-carcinoembryonic antigen in colorectal cancer].

This investigation is a part of a phase three multicentre immunoscintigraphy study of a technetium-99m labelled monoclonal antibody (Mab), BW 431/26, directed against carcino-embryonic antigen (CEA). Ten patients with recently colonoscopically verified primary colorectal cancer were evaluated. In nine of ten patients colorectal cancers were detected by wholebody immunoscintigraphy and by single photon emission computerized tomography (SPECT). The ten patients were operated upon, and in nine cases immunohistochemical investigations were performed. Immunohistochemical investigation of nine tumour specimens show that CEA was present in much higher concentrations in the tumour than in normal intestinal epithelium. Active accumulation of the labelled Mab in tumours was demonstrated by scintimetry. There is a demand for new diagnostic techniques for early diagnosis of colo-rectal cancer. Immunoscintigraphy must however compete with other diagnostic possibilities. The development of immunoscintigraphic technique is proceeding very rapidly, and there is probably a future for the use of immunological methods in diagnosis and therapy of cancer.

Antibodies, Monoclonal↗
PubMed1994

Clonal karyotypic abnormalities in colorectal adenomas: clues to the early genetic events in the adenoma-carcinoma sequence.

Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and together with other numerical changes in another. A +7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were -14 and -18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only numerical changes. The chromosome most often involved in structural aberrations was chromosome 1. In 6 cases, the rearrangements led to changes in 1p, always with loss of material. The breakpoints were at 1p32-36. One adenoma had deletion of 1p as the only change. Other chromosomes that were involved in changes in more than 2 cases were chromosomes 8, 13, and 17. These rearrangements typically led to gain of 8q and 13q and loss of 17p. The adenomas with structural abnormalities were generally larger and had a higher degree of dysplasia than did the adenomas with numerical changes only or those with a normal karyotype. All adenomas with a tubulovillous or villous architecture had structural rearrangements. Our findings confirm that a subset of colorectal adenomas exists that have only numerical chromosome aberrations. They also support our previous conclusion that loss of material from distal 1p is an early event in colorectal tumorigenesis, but that other cytogenetic aberrations follow and typically are present already at the adenomatous stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Digital rectal examination and transrectal ultrasonography in staging of rectal cancer. A prospective, blind study.

Staging of rectal carcinoma before surgical treatment was performed in a prospective blind study, comparing digital rectal exploration and transrectal linear ultrasonography (TRUS) with the resulting pathological examination. TRUS underestimated depth of penetration in 3 of 33 patients and overestimation resulted in 9 of 74. The figures for digital examination were 5 of 18 and 20 of 76, respectively. Penetration of the rectal wall was correctly identified in 56 of 61 patients by digital examination and in 59 of 61 by TRUS. Specimens without penetration of the rectal wall were identified in 26 of 33 patients by TRUS, but in not more than 13 of 33 by digital examination. Regional lymph node metastases were present in 19 patients; none were diagnosed by digital examination, but TRUS identified 11 of the 19. It is concluded that TRUS will result in more patients having the possibility of local surgery for cure.

Female↗
PubMed1993

Tumor detection with 131I-labeled human monoclonal antibody COU-1 in patients with suspected colorectal carcinoma.

A major factor limiting the use of rodent monoclonal antibodies for diagnosis and therapy of cancer is the development of human anti-mouse immunoglobulin antibodies. Here we report a phase I/II immunodetection study of a human monoclonal antibody, COU-1, labeled with 131I. COU-1 is produced by a human-human hybridoma and recognizes a M(r) 43,000 cytokeratin-like protein strongly expressed by adenocarcinomas of the colon, breast, and ovary. Ten patients were given an i.v. infusion of 2 mg of antibody COU-1 labeled with 185 MBq of 131I. No adverse effects or toxicity were detected by conventional clinical tests nor by a complement activation assay for C3d. None of the patients developed antibodies against antibody COU-1 as determined by enzyme-linked immunosorbent assay and agglutination analysis. Tumor detection was successful in 7 of 9 cancer patients. The tenth patient proved to be a true negative. In several instances immunoscintigraphy gave additional or more correct information than conventional detection techniques. Tumors were most clearly outlined at days 5 and 7 after infusion. Primary colorectal carcinomas were detected by planar imaging in the cecum, ascending colon, and rectum with the smallest lesion measuring 3.0 cm in diameter. Immunoscintigraphy revealed multiple liver metastases in 1 of 3 patients. However, the livers of all 3 patients contained significantly more radioactivity (P < 0.005) than tumor-free livers of the other patients. Pharmacokinetics was evaluated in all patients. The clearance of 131I-labeled COU-1 from the circulation followed a triphasic pattern; an initial phase [t1/2 = 0.4 +/- 0.4 (SD) h] cleared 23% of the radioactivity followed by a rapid phase with a half-life of 13 +/- 3.8 h. The third phase (beta-phase) exhibited a half-life of 119 +/- 36 h, which is similar to the half-life reported for normal IgM. The human monoclonal antibody COU-1 directed against a predominantly intracellular cancer-associated antigen does not produce toxicity or induce antibody formation and seems to be a promising agent for detecting tumors with immunoscintigraphy.

Animals↗
PubMed1993

Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis.

Cytogenetic analysis of short-term cultures from benign intestinal tumors revealed clonal chromosome aberrations in five colorectal adenomas, one adenoma of the papilla Vateri, and one hyperplastic polyp of the rectum. One adenoma had numerical aberrations only, but in all other tumors structural rearrangements were found that led to loss of genetic material from 1p. In three of the cases, the deletion was restricted to the 1p36 band; the rest had lost larger 1p segments. The rearrangement of chromosome 1 was the sole karyotypic anomaly in three adenomas, all with mild or moderate dysplasia, and in the hyperplastic polyp. Both adenomas that had additional aberrations beyond the 1p loss showed severe dysplasia. We conclude that cytogenetically detectable loss of genetic information from 1p36 is an early, seemingly primary, premalignant event in intestinal tumorigenesis. The fact that the adenomas with 1p- as the sole change showed only mild or moderate dysplasia and that the del(1p) was found also in the hyperplastic polyp suggests that this aberration is more related to the induction of hyperproliferation than to differentiation disturbances in the intestinal mucosa.

Adenoma↗
PubMed1993

[Liver disease in erythropoietic protoporphyria].

In erythropoietic protoporphyria, the genetically determined decreased activity of the enzyme ferrochelatase causes accumulation of the photoreactive molecule protoporphyrin in various tissues. Dermatological symptoms are dominant, but in some patients the excess protoporphyrin affects hepato-biliary structures, and a spectrum of changes, which ranges from ultrastructural bile canalicular damage to cirrhosis, can be observed. Most clinical reports have described severe cases with a rapid deterioration and a fatal outcome. We present a case with spontaneous recovery from hepatic decompensation on two occasions with three years interval. The first incidence might have been provoked by hormonal substitution therapy.

Female↗
PubMed1993

The Funen Adenoma Follow-Up Study. Characteristics of patients and initial adenomas in relation to severe dysplasia.

Between 1978 and 1992 a total of 1689 colorectal adenomas were removed in 1042 patients with no history of previous colorectal neoplasms. One hundred and eighteen patients had at least one adenoma with severe dysplasia. A 'clean colon' was ensured by total colonoscopy in 97% of the patients. A multiple logistic model was used to assess the independent risk factors associated with severe dysplasia. The size of largest adenoma and the extent of villous component were identified as independent patient risk factors associated with high risk of severe dysplasia. The results indicated that the risk of severe dysplasia is high in patients with large and/or villous adenomas and the risk is even higher when the adenomas are found in the sigmoid colon or rectum.

Adenoma↗