Plasma basic fibroblast growth factor levels in colorectal cancer: a clinically useful assay?

Angiogenic cytokines in the plasma and serum of cancer patients may serve as 'surrogate' markers of tumour neoangiogenesis. Serum VEGF correlates with disease stage in colorectal cancer (CRC), but the role of bFGF in CRC is uncertain. This study aimed to assess plasma bFGF levels in CRC patients before treatment, during chemoradiotherapy and at one-year follow-up. Plasma samples were taken from 124 CRC patients, 26 polyp patients and 55 controls, and bFGF levels were measured by ELISA. 19 patients underwent pre-operative chemoradiotherapy. One-year follow-up samples were available from 48 disease-free patients and 18 patients with progressive disease. There were no detectable differences between plasma bFGF levels in polyp, Dukes' A or B patients (4.55, 5.77, 4.25 pg/ml, respectively), but there was a significant increase in metastatic CRC patients [Dukes' C and D (7.42 and 6.6 pg/ml; P = 0.004 and 0.048, respectively)], relative to median control levels of 4.14 pg/ml. At follow-up, there was a significant fall in plasma bFGF levels in disease-free patients (pre-op 6.09 and follow-up 3.45 pg/ml, P = 0.0004), but a non-significant rise in 18 patients with progressive disease (pre-treatment 5.90 and follow-up 9.99 pg/ml, P = 0.33). Pre-treatment plasma bFGF in patients receiving chemo-radiotherapy was similar in those with responsive and non-responsive tumours. There were no detectable changes in plasma bFGF through the adenoma-carcinoma sequence or patient groups with non-metastatic cancers. Elevated plasma bFGF was, however, associated with metastatic spread. The significant fall in bFGF in disease-free patients following therapy suggests that bFGF may be useful in clinical practice.

VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression.

We aimed to assess the relationship of the angiogenic cytokines VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR-2 and VEGFR-3 in the adenoma-carcinoma sequence and in metastatic spread of colorectal cancer (CRC). mRNA expression levels were measured using semi-quantitative reverse transcription polymerase chain reaction in 70 CRC (35 with paired mucosae) and 20 adenomatous polyps. Immunohistochemistry and ELISA assessed protein expression. VEGF-D mRNA expression was significantly lower in both polyps and CRCs compared with normal mucosa (P=.0002 and.002, respectively), whereas VEGF-A and VEGF-C were significantly raised in CRCs (P=.006 and.004, respectively), but not polyps (P=.22 and P=.5, respectively). Receptor expression was similar in tumor tissue and normal mucosae. Tumors with lymph node metastases had significantly higher levels of VEGF-A compared with non-metastatic tumors (P=.043). There was no association between VEGF-C or VEGF-D and lymphatic spread. The decrease in VEGF-D occurring in polyps and carcinomas may allow the higher levels of VEGF-A and VEGF-C to bind more readily to the VEGF receptors, and produce the angiogenic switch required for tumor growth. Increased expression of VEGF-A within CRCs was associated with lymphatic metastases, and therefore, this member of the VEGF family may be the most important in determining metastatic spread.

Solitary pancreatic metastasis from a primary colonic tumor detected by PET scan: report of a case.

PURPOSE: A case of a solitary pancreatic metastasis from a primary colonic carcinoma is reported. METHODS: The history and use of carcinoembryonic antigen, computed tomography, and positron emission tomography in this case and the follow-up of colorectal cancer are reviewed. RESULTS: Recurrent disease was suspected by an increasing carcinoembryonic antigen level. However, conventional imaging with computed tomography on more than one occasion failed to identify any recurrence. The pancreatic metastasis was accurately localized by positron emission tomography scanning and confirmed on subsequent laparotomy. A histologically complete resection was performed and the patient remained in remission with a normal carcinoembryonic antigen 12 months postoperatively. CONCLUSION: This case reports an unusual site of solitary metastasis in colorectal cancer and supports the further investigation of positron emission tomography in follow-up of colorectal cancer.

Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging?

Most studies measuring circulating vascular endothelial growth factor (VEGF) have sampled serum rather than plasma. There has been much debate whether the collection of sera (which causes the activation of platelets and VEGF release) is a true reflection of tumor angiogenic activity or whether platelets act as scavengers of VEGF. Addressing this issue, we measured serum and plasma VEGF, before and after colorectal resection, with reference to platelet counts. Serum and plasma samples were collected from 116 colorectal cancer (CRC) and 116 control patients. Ninety CRC and 32 benign resections were performed. Both plasma and serum VEGF were significantly higher in CRC patients (18.5 and 327 pg/ml, respectively) compared with controls (9.0 and 151.5 pg/ml, respectively; P < 0.0001). Paired serum and plasma VEGF measurements correlated in both CRC (r = 0.56) and control patients (r = 0.73; P < 0.0001). Serum and plasma VEGF levels correlated with platelet count in CRC patients (r = 0.58 and 0.44, respectively) but not in controls. Plasma and serum VEGF levels, and VEGF concentration per platelet, increased with advancing disease stage. The correlation of serum and plasma VEGF with platelet counts in CRC but not in benign disease may be attributable to the scavenging of VEGF from the tumor source by platelets, with plasma levels reflecting free circulating VEGF in equilibrium with platelet levels. VEGF levels in citrated plasma are low and lie close to the limits of ELISA sensitivity. We recommend that a standardized measurement of serum VEGF--normalized by the patient's platelet count to give a value of serum VEGF per platelet--be adopted.

Screwdriver assaults and intracranial injuries.

Four patients with intracranial penetrating injuries from screwdrivers are presented. Two cases were fatal; the others were left with functional deficits. In two of the patients a penetrating injury was not suspected initially because the history was limited and the significance of the small entry wounds were not appreciated. Unless these wounds are carefully examined a penetrating injury is easily overlooked.

Morphology of oligodendrocytes during demyelination in optic nerves of mice infected with Semliki Forest virus.

Multiple sclerosis (MS) is a demyelinating disease which affects oligodendrocytes, the myelinating cells of the CNS. Demyelination is known to occur in the optic nerves of Balb/c mice infected with the avirulent A7(74) strain of Semliki Forest virus (SFV), and many of the changes are similar to those of patients with MS. The aim of the present study was to determine how demyelination proceeds in individual oligodendrocytes in SFV infection, to help in understanding the pathology of demyelination and remyelination in MS. The whole-cell morphology of individual oligodendrocyte units (defined as the oligodendrocyte, its processes and the internodal myelin segments of the axons it ensheaths) was characterized using intracellular dye injection in isolated intact optic nerves. In untreated control mice, oligodendrocytes had a relatively uniform morphology and each cell on average provided 20 or so nearby axons with single myelin sheaths with internodal lengths of approximately equal to 150 microns. In SFV infected mice, during the peak of demyelination at post-inoculation days 14-21, 55% of oligodendrocytes displayed a range of morphological abnormalities, which most likely represented sequential changes in oligodendrocytes during demyelination. Thus, at the earliest stage of demyelination oligodendrocytes developed swellings or vacuolations along their internodal myelin sheaths, which became gradually attenuated and were completely lost in extreme cases. The results show that whole oligodendrocyte units were affected during SFV-induced demyelination and this is the basis of the focal nature of lesions in this viral model of MS. Individual oligodendrocyte units which had lost their full complement of myelin sheaths had the appearance of immature oligodendrocytes, suggesting they had undergone dedifferentiation. We concluded that these cells may not be destroyed during demyelination and it is possible they are capable of remyelination which is a feature of SFV infection in mice and MS in humans.