Search PubMed⌕ Search

Biomedical subjects

A M Abulafi

Publications and source records attributed to A M Abulafi.

17 recordsLinked to original sources

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.

Biomarkers, Tumor↗

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.

Adenocarcinoma↗

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.

Adult↗

The role of colonoscopy in coloproctological practice.

Colonoscopy has completely changed the practice of colorectal surgery. It has both diagnostic and therapeutic roles. In diagnosis, it allows direct visualization of the colon and taking of tissue biopsies for histology. The commonest therapeutic manoeuvre is polypectomy for bleeding. Colonoscopy is safe and, where facilities exist, it should be used as first-line investigation of colorectal disorders.

Colon↗

Adjuvant intraoperative photodynamic therapy in experimental colorectal cancer using a new photosensitizer.

BACKGROUND: Photodynamic therapy is a promising anticancer modality. The effect of adjuvant intraoperative photodynamic therapy (AIOPDT) using photosensitizers Photofrin or mesotetra (hydroxyphenyl) chlorin (m-THPC) was evaluated in a mouse model of local recurrence of colorectal cancer. METHODS: Animals were injected with either photosensitizer 24 h before surgery. Standard excision included removal of all visible tumour by a surgeon blinded to both the drug and subsequent light treatment. Following surgery the tumour beds were illuminated with either 70 J cm-2 of 510-nm light (Photofrin) or 2.5 J cm-2 of 652-nm light (m-THPC). Control groups had either surgery only, surgery and Photofrin only, surgery and m-THPC only, or surgery and either 652-nm or 510-nm light. RESULTS: After a 70-day observation period, the local recurrence rates were 25-26 per cent in the photodynamic therapy groups compared with 80-90 per cent in the control groups (P < 0.001). CONCLUSION: AIOPDT using either Photofrin or m-THPC was equally effective in reducing local recurrence in this model. Since treatment time with m-THPC was only 25 s compared with 11 min with Photofrin, the use of the former new photosensitizer increases the practicality of AIOPDT and could enable the laser to be replaced with cheaper, less intense light sources.

Animals↗

Adjuvant intraoperative photodynamic therapy in experimental colorectal cancer.

A reliable animal model for quantitative assessment of local recurrence of colorectal cancer was developed using colo26 tumour in BALB/c mice. The effect of adjuvant intraoperative photodynamic therapy to potentially curative surgery on local recurrence was examined in four study and four control groups. Study groups received 15 mg kg-1 Photofrin (a photosensitizing drug) 24 h before surgery. After 'curative' tumour excision, the tumour beds were illuminated with either 630 nm or 510 nm laser light each at 40 and 70 J/cm-2. Controls received surgery only, surgery and Photofrin only or surgery and either 630 nm or 510 nm light. The local recurrence rates at 70 days were 17-33 per cent in the study groups compared with 83-100 per cent in the control groups (P < 0.001; log rank test). Photodynamic therapy is capable of reducing local recurrence following potentially curative excision of tumour in this model.

Animals↗

Photodynamic therapy for malignant tumours of the ampulla of Vater.

Ten patients with ampullary carcinoma, not suitable for surgery, were treated with endoscopic photodynamic therapy (PDT) to evaluate the feasibility and safety of treatment. Patients received 4 mg kg-1 of haematoporphyrin derivative intravenously. Two days later, a duodenoscopy was performed and red (630 nm) light delivered to the tumour at fixed energy densities of 50 J or 200 J cm-1 per application, depending on the type of optical fibre used. The tumours were treated by three or four light applications at each session. Treatment was repeated up to five times at intervals of three to six months. The sole complication of PDT was moderate skin photosensitivity, which occurred in three patients. Tumour size was assessed at four to eight weekly intervals. In the absence of macroscopic tumour, biopsy specimens were taken. In three patients with small tumours confined to the ampulla, remission was obtained for periods ranging from eight to 12 months. In a further four patients with small tumours bulk was greatly reduced. There was little response in three patients with extensive duodenal involvement. Therefore PDT for ampullary carcinoma is both feasible and safe, and with refinement may prove curative for small tumours.

Aged↗

Local recurrence of colorectal cancer: the problem, mechanisms, management and adjuvant therapy.

Local recurrence of colorectal cancer after 'curative' surgery is a major clinical problem. Typically, 50-70 per cent of patients presenting to a surgical clinic will undergo apparently curative surgery for disease and of these about 10-25 per cent will develop local recurrence, in either the tumour bed or bowel wall. The wide differences in local recurrence rate both between and within institutions is probably caused by variation in surgical technique. The main causes of local recurrence are inadequate excision of the primary tumour or the draining lymph nodes, and intraoperative tumour cell implantation. The most significant single factor prognostic of local recurrence is Dukes' tumour stage. Other important factors include tumour grade and fixity, level of the tumour in the rectum, blood and lymphatic vessel invasion, inadvertent perforation of the tumour during resection, and the surgeon's experience. The prognosis of patients with local recurrence is poor. Prevention of recurrence by adequate surgery and adjuvant therapy as well as its early detection offer the best prospect of improving results.

Antineoplastic Agents↗

Adjuvant intraoperative photodynamic therapy for colorectal carcinoma: a clinical study.

The local recurrence rate of colorectal carcinoma after surgery is unacceptable in most series, and adjuvant therapies have made only a small impact on this. There is experimental evidence that adjuvant intraoperative photodynamic therapy (AIOPDT) may be effective. AIOPDT involves systematically photosensitizing the patient preoperatively with a drug (HpD) which relatively localizes to tumour and is activated using visible light. At operation the resected tumour bed is illuminated with a predetermined uniform light energy density to eradicate microscopic tumour deposits left at the lateral resection margin. We have previously investigated technical and biological factors leading to this clinical trial. Seventeen patients have received AIOPDT in a potentially effective dose, and safety and technical matters have been investigated. Cutaneous phototoxicity occurred in 3 patients. Three patients had anastomotic breakdown, none considered attributable to PDT. The intraoperative technique was a practical option. AIOPDT carried a low patient morbidity and should be investigated in prospective clinical trials to determine if local recurrence rates can be decreased.

Aged↗

Accurate measurement of surface areas of anatomical structures by computer-assisted triangulation of computed tomography images.

There is a need for accurate surface area measurement of internal irregular anatomical structures in order to define light dosimetry in adjunctive intraoperative photodynamic therapy (AIOPDT). No satisfactory preoperative method exists of measuring this parameter. We have investigated whether computer-assisted triangulation of serial sections generated by computed tomography (CT) scanning can give an accurate assessment of the surface area of the walls of the true pelvis after anterior resection and before colorectal anastomosis. We have shown that the technique of paper density tessellation is an acceptable method of measuring the surface areas of phantom objects, with a maximum error of 0.5%, and is used as the gold standard. Computer-assisted triangulation of CT images of standard geometric objects and accurately-constructed pelvic phantoms gives a surface area assessment with a maximum error of 2.5% compared with the gold standard. The CT images of 20 patients' pelves have been analysed by computer-assisted triangulation and this shows that the surface area of the walls varies from 143 cm2 to 392 cm2. Simple step-like analysis of images and approximation to geometric shapes with subsequent calculation give unacceptably high errors. The surface area of an internal, rigid, irregular surface area for illumination in AIOPDT can be accurately measured preoperatively by computer-assisted triangulation of CT images.

Anthropometry↗

Leaking abdominal aortic aneurysm presenting as an inguinal mass.

Two patients with leaking abdominal aortic aneurysm (AAA) presenting as a tender inguinal mass are reported. Unusual presentations such as this often cause delays in definitive surgery which result in increased morbidity and mortality. It follows that the diagnosis of a leaking AAA should be considered in all patients with a tender pulsatile abdominal mass regardless of the presentation.

Aged↗

Malignant lymphoma in ulcerative colitis. Report of a case.

The authors present the case of a 40-year-old woman with primary malignant lymphoma complicating chronic ulcerative colitis. Twenty-one cases reported in the literature are reviewed and the various available data analyzed. Variations in the distribution of lymphoma in both the normal and colitic bowel supports a relationship between both conditions. Any lymphocytic infiltrate seen in biopsies obtained from ulcerative colitis should be assessed to exclude associated lymphoma. The prognosis is poor.

Adult↗

Délorme's operation for rectal prolapse.

Between 1981 and 1988 inclusive, 22 patients with full-thickness rectal prolapse presenting to two surgeons in this hospital were treated using the Délorme operation. There was no mortality and morbidity was minimal. Twenty-one patients (95.5%) were cured of prolapse and 19 patients (86.4%) had normal anal sphincter function after the operation.

Adult↗

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.

Adenomatous Polyps↗