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Biomedical subjects

P B Boulos

Publications and source records attributed to P B Boulos.

At least 37 records · Page 2Linked to original sources

Progressive loss of perivascular nerves adjacent to colorectal cancer.

AIMS: The perivascular innervation of arterioles in colorectal cancer and adjacent submucosa was investigated. METHODS: Neurotransmitter markers, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), were studied and immunoreactivity was compared with that of control normal tissue. RESULTS: There was absence of perivascular nerves within tumours and loss of perivascular innervation in the submucosa adjacent to the tumour. The pattern of loss varied for different transmitters. The loss was progressively greater with advancing tumour stage for NPY (controls 95%, Dukes' A 68%, Dukes>> B 13%, Dukes' C 6%) and VIP (50%, 23%, 20%, 17%). For TH there was extensive loss of innervation around tumours of all stages (69%, 5%, 7%, 0%). SP immunoreactive peri-arteriolar nerves were similar in control tissue (39%) and tissue adjacent to Dukes' A tumours (40%) but diminished to 19% and 0% in tissue adjacent to Dukes' B and C tumours, respectively. In none of the tissues was CGRP immunoreactivity above 4%. The mean distance over which there was reduced NPY immunoreactivity from the tumour edge was 2.43 mm for Dukes' A/B tumours compared with 7.20 mm for Dukes' C tumours; for VIP immunoreactivity this distance was 5.22 mm for Dukes' A/B tumours and 5.52 mm for Dukes' C tumours. CONCLUSIONS: The progressive loss, both in terms of vascular nerve immunoreactivity and distance from the tumour edge with tumour grade, suggests that the tumour itself may influence neural integrity in perivascular plexuses, perhaps via the secretion of an inhibitory factor.

Aged↗

Neuromyogenic properties of the internal anal sphincter: therapeutic rationale for anal fissures.

Lateral sphincterotomy diminishes internal anal sphincter hypertonia and thereby reduces anal canal pressure. This improves anal mucosal blood flow and promotes the healing of anal fissures. However, sphincterotomy can be associated with long term disturbances of sphincter function. The optimal treatment for an anal fissure is to induce a temporary reduction of anal canal resting pressure to allow healing of the fissure without permanently disrupting normal sphincter function. Broader understanding of the intrinsic mechanisms controlling smooth muscle contraction has allowed pharmacological manipulation of anal sphincter tone. We performed an initial Medline literature search to identify all articles concerning "internal anal sphincter" and "anal fissures". This review is based on these articles and on additional publications obtained by manual cross referencing. Internal anal smooth muscle relaxation can be inhibited by stimulation of non-adrenergic non-cholinergic enteric neurones, parasympathetic muscarinic receptors, or sympathetic beta adrenoceptors, and by inhibition of calcium entry into the cell. Sphincter contraction depends on an increase in cytoplasmic calcium and is enhanced by sympathetic adrenergic stimulation. Currently, the most commonly used pharmacological agent in the treatment of anal fissures is topical glyceryl trinitrate, a nitric oxide donor. Alternative agents that exhibit a similar effect via membrane Ca2+ channels, muscarinic receptors, and alpha or beta adrenoceptors are also likely to have a therapeutic potential in treating anal fissures.

Anal Canal↗

Effect of colonic obstruction on the distribution of matrix metalloproteinases during anastomotic healing.

BACKGROUND: Anastomotic dehiscence is common after surgery for colonic obstruction. The strength of an anastomosis is dependent on collagen, which is degraded by matrix metalloproteinases (MMPs). The aim of this study was to determine the distribution of the MMPs and their inhibitor, tissue inhibitor of metalloproteinases (TIMP) 1 in an experimental model of colonic obstruction, with and without resection and anastomosis. METHODS: The distal colon of rabbits was obstructed with a Silastic ring for 24 h and then either the ring was removed or the obstructed segment was resected and an anastomosis formed. Rabbits were killed immediately or at intervals for up to 7 days after operation. The distribution of the MMPs and TIMP-1 was examined by indirect immunofluorescence. RESULTS: MMPs and TIMP-1 were present throughout the descending colon for 24 h in both groups. They persisted to the third day in rabbits with an anastomosis but by day 7 were restricted to the suture line. Their presence correlated with microscopic damage. CONCLUSION: The extensive distribution of the MMPs suggests that these enzymes contribute to anastomotic dehiscence, but only in the immediate postoperative period.

Anastomosis, Surgical↗

Raised endothelin 1 levels in patients with colorectal liver metastases.

BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.

Aged↗

Metachronous colorectal cancers.

BACKGROUND: Up to 9 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers. There is no consensus on the detection and management of such cancers. METHODS: The literature was reviewed exhaustively regarding the incidence, clinical characteristics, detection, treatment and molecular genetics of metachronous colorectal cancers. This was based on a Medline search from 1966 to December 1997 for articles on metachronous colorectal cancers. A manual search was also performed on references quoted in these articles. All publications relevant to this study were included. RESULTS: Although the underlying causes for metachronous colorectal cancers are yet to be elucidated, risk factors for the disease have been identified. These include the presence of synchronous polyps or cancers, a history of metachronous cancers, and hereditary non-polyposis colorectal cancer (HNPCC). CONCLUSION: Preoperative colonoscopy and postoperative colonoscopic surveillance are essential in identifying patients at risk of metachronous colorectal cancer. A total colectomy and ileorectal anastomosis should be considered for some patients, certainly for those with HNPCC.

Colorectal Neoplasms↗

Helical CT pneumocolon to assess colonic tumors: radiologic-pathologic correlation.

OBJECTIVE: The objective of this study was to determine the accuracy of helical CT pneumocolon in the staging of colonic carcinomas. SUBJECTS AND METHODS: Fifty-two patients (27 men, 25 women; age range, 40-88 years old; mean age, 67 years old) with known or strongly suspected colonic disorders underwent CT pneumocolon. After bowel cleansing, administration of smooth muscle relaxant, and rectal air insufflation, CT pneumocolon was performed with 5-mm collimation, 2.5-mm reconstruction interval, and a pitch of 1.5. Two contrast administration protocols were used. Twelve patients received 100 ml of i.v. contrast material that was injected at 3 ml/sec; scan delay was 45 sec. The other 40 patients received 150 ml of contrast material at 5 ml/sec; scan delay was 25 sec. Images were prospectively evaluated. All patients had pathologic confirmation: 46 patients had resections and six patients had endoscopic biopsies. RESULTS: Diagnostic images were obtained in 47 of 52 patients. In the 47 patients, there were 38 colonic carcinomas (one synchronous), nine diverticular strictures, eight polyps, one ischemic stricture, and one normal study. Thirty of 38 carcinomas were correctly staged by CT. Sensitivity and specificity for serosal infiltration were 100% (35/35 carcinomas) and 33% (one of three carcinomas), respectively; sensitivity and specificity for lymph node involvement were 56% (nine of 16 carcinomas) and 95% (21/22 carcinomas), respectively. Four polyps that were smaller than 5 mm in diameter were not revealed by CT. Twelve of 14 benign lesions were correctly diagnosed and two were believed to be malignant. No malignant lesion was misdiagnosed. CONCLUSION: CT pneumocolon gave an overall staging accuracy of 79% in 38 carcinomas.

Adult↗

Genetic instability in patients with metachronous colorectal cancers.

BACKGROUND: Nearly 7 per cent of patients who undergo resection for colorectal cancer develop metachronous cancers several years later. A molecular marker that could identify patients susceptible to metachronous cancers would be of clinical importance. METHODS: Twenty-four colorectal cancers from 15 individuals with metachronous colorectal cancer were investigated for microsatellite instability at five loci by single stranded conformational polymorphism analysis. A control group of 14 colorectal cancers from individuals who had only developed one sporadic colorectal cancer each was analysed similarly. RESULTS: Microsatellite instability was demonstrated in 17 of 24 cancers from individuals with metachronous cancer compared with one of 14 cancers from individuals with a single colorectal cancer. CONCLUSION: These results suggest that testing for microsatellite instability may be useful in recognizing patients at high risk of developing metachronous colorectal cancers.

Aged↗

Role of matrix metalloproteinases in healing of colonic anastomosis.

PURPOSE: The aim of this study was to compare the distribution of the matrix metalloproteinases (MMPs) during anastomotic healing in a normal colon with that in an ischemic colon in a rabbit. This family of enzymes degrades all components of connective tissue and has been implicated as a cause of anastomotic dehiscence. METHODS: A left-sided anastomosis was formed in the distal colon of one group of rabbits, and in the other group, 9 cm of distal colon was made ischemic before resection and anastomosis 12 hours later. Tissues from the anastomosis and sites around the colon were removed at 12 hours, 1 day, and 3 days after anastomosis and, also, at 7 days in the normal group. Distribution of the MMPs and their inhibitor, tissue inhibitor of metalloproteinases (TIMP), was localized by indirect immunofluorescence. RESULTS: In rabbits having only an anastomosis, the MMPs and TIMP-1 were, at all times, seen solely in the anastomotic segment and were strictly confined to the immediate vicinity of the suture line. While in rabbits with an ischemic colon before anastomosis, the MMPs initially extended several centimeters proximally and distally from the suture line. By the third day, however, there were only minor differences between the two models. CONCLUSION: Distribution of the MMPs and TIMP-1 in normal healing is consistent with a role in the remodeling of colonic anastomosis, but when healing of the colon is compromised, these enzymes are more widespread and may contribute to anastomotic dehiscence.

Anastomosis, Surgical↗

Neurochemical coding in the small intestine of patients with Crohn's disease.

BACKGROUND: There have been conflicting results regarding the effect of Crohn's disease on the neurochemical composition of the enteric nervous system. AIMS: To examine the effect of Crohn's disease on the neurochemical composition of enteric nerve fibres and cell bodies using whole mount preparations of human ileum. METHODS: Whole wall ileum from seven normal subjects and nine patients with Crohn's disease was used to investigate the neurochemical composition of neurones and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of ileum using immunohistochemical techniques. RESULTS: Increased tyrosine hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was exclusively seen in the myenteric plexus. There was increased neurofilament immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle layer, and thick bundles of immunoreactive nerve fibres in the serosa layer. Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary adenylate cyclase activating peptide immunoreactivity was seen in the myenteric plexus and nerve fibres of the circular muscle layer, and aggregates of inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum. In addition, there was a chaotic display of nerve fibres containing some of the neuroactive substances with a high frequency of enlarged varicosities in the myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's ileum. CONCLUSION: Results show quantitative as well as qualitative changes in the neurochemical composition of enteric nerve fibres and nerve cell bodies of Crohn's ileum. These changes and the presence of nitric oxide synthase and peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve-immune interactions may have a significant role in the process of the inflammatory changes seen in Crohn's ileitis.

Adult↗

Technical report: spiral CT pneumocolon for suspected colonic neoplasms.

Abdominal spiral computed tomography (CT) pneumocolon is performed after cleansing the colon, using a smooth muscle relaxant and rectal air insufflation. Rapid dynamic scanning is undertaken with intravenous contrast to give optimal hepatic and vascular enhancement, and 5-10 mm contiguous slices. The area of interest in the colon is reconstructed every 2.5 mm. This technique was performed in four patients with colorectal cancer and the CT findings were compared with the barium enema and pathology following surgical resection. Spiral CT pneumocolon clearly showed the primary tumour in all cases as an enhancing soft tissue mass, and was able to detect local extension and lymphadenopathy as well as assess the liver, peritoneum and remaining abdomen. CT depicted the morphology of the primary tumour more clearly than barium enema, and in one case also detected a 1 cm polyp which was not seen on the barium study because the patient was incontinent of barium and views were limited. There was good correlation between the CT and pathological findings. Compared to a barium enema, spiral CT pneumocolon is quick, with minimal patient discomfort, no risk of barium incontinence, and there is good assessment of the local and distant abdominal disease. Multiplanar formatting is possible and 3-D reconstruction gives intra- and extra-luminal views.

Aged↗

[The effect of the physico-chemical properties of suture materials and the surface structure on adherence of tumor cells].

Local recurrence following curative resection for colorectal cancer may be caused by the seeding of free malignant cells at the anastigmatic site. This study investigated the influence of suture material on in vitro tumor cell adherence. Radiolabeled rat colonic cancer cells (RCC5) were incubated with a variety of suture materials, and the relative contribution of chemical composition and physical configuration to cell adherence was assessed. Nonadherent cells were washed free, and the cell adherence was determined by radioactive counting. Marked differences in adherence were observed, with cells preferentially adhering to protein-based and multifilament sutures. These observations were confirmed using scanning electron microscopy. These findings indicate that both chemical composition and physical configuration influence the adherence of tumor cells to sutures and suggest that the use of protein-based and multifilament sutures be carefully considered in situations where free malignant cells may be present following colorectal surgery.

Animals↗

Influence of temporary faecal diversion on long-term survival after curative surgery for colorectal cancer.

Experimental carcinogenesis is enhanced at colorectal anastomoses, inhibited by proximal faecal diversion and promoted by the closure of a defunctioning stoma. The clinical relevance of these observations was investigated in a retrospective study of curative restorative resection for colorectal carcinoma. The 5-year disease-free survival rate (95 per cent confidence interval) in 122 patients with a temporary stoma (50.4 (41.1-59.7) per cent) was significantly reduced (P < 0.01) compared with that in 218 with no stoma (66.8 (59.4-73.5) per cent). In patients with Dukes B tumours early stoma closure (within 3 months of resection) was associated with a worse survival (P < 0.005) and a higher tumour recurrence rate (P < 0.05) than in those with no stoma. Survival rates after late stoma closure were no different from those in patients with no stoma. Multivariate analysis revealed Dukes stage (P < 0.0001), tumour differentiation (P = 0.02) and timing of stoma closure (P = 0.02) as independent predictors of survival. In curative surgery for colorectal cancer temporary faecal diversion confers a survival disadvantage that can be prevented by delayed closure of the stoma.

Adenocarcinoma↗

The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer.

Studies suggest that the interplay between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs) is an important mediator of tumour invasion and metastasis. Using immunohistochemistry, 40 specimens of colorectal cancer were examined for the presence of TIMP-1 and the MMPs, stromelysin, gelatinases A and B and interstitial collagenase. Neither enzyme nor TIMP-1 was detected in histologically normal mucosa. Within malignant tissue, stromelysin and gelatinase A were conspicuously absent in tumor cells but were immunolocalized to the extracellular matrix and for gelatinase A also to peritumoural fibroblast-like cells. Gelatinase B was confined to polymorphonuclear leucocytes. Interstitial collagenase was not identified. TIMP-1 was present in only three of the 40 tumours within the malignant stroma. These observations suggest that the mesenchymal elements of colorectal carcinomas, by acting as a source of MMPs and TIMPs, may modulate tumour invasion.

Collagenases↗

The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer.

Studies suggest that the interplay between matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), is an important mediator of tumour invasion and metastasis. Using immunohistochemistry, 40 specimens of colorectal cancer were examined for the presence of TIMP-1 and the MMPs, stromelysin, gelatinases A and B and interstitial collagenase. Neither enzyme nor TIMP-1 was detected in histologically normal mucosa. Within malignant tissue, stromelysin and gelatinase A were conspicuously absent in tumour cells but were immunolocalized to the extracellular matrix and for gelatinase A also to peritumoural fibroblast-like cells. Gelatinase B was confined to polymorphonuclear leucocytes. Interstitial collagenase was not identified. TIMP-1 was present in only three of the 40 tumours within the malignant stroma. These observations suggest that the mesenchymal elements of colorectal carcinomas, by acting as a source of MMPs and TIMPs, may modulate tumour invasion.

Collagenases↗

Intra-abdominal sepsis and survival after surgery for colorectal cancer.

Of 361 patients who survived curative left colonic or sphincter-saving rectal resection for cancer, 44 developed significant postoperative intra-abdominal sepsis and 317 did not. The two groups were well matched for age, sex, site of tumour, Dukes stage, tumour differentiation and timing of operation. There was no significant difference in the 5-year overall actuarial survival rate (P = 0.25) or in the 5-year disease-free survival rate (P = 0.23). Stepwise regression analysis of prognostic variables including age, sex, site of tumour, Dukes stage, tumour differentiation, timing of operation, grade of surgeon and postoperative intra-abdominal sepsis identified Dukes stage, age at operation and tumour differentiation as predictors of survival. These results suggest that postoperative intra-abdominal sepsis is not a prognostic factor for long-term survival in colorectal cancer as has been previously reported.

Abdomen↗

Effects of the H2-antagonists famotidine and nizatidine and the cytoprotectant misoprostol on human colonic and rat peritoneal mast cells.

The H2-antagonists famotidine and nizatidine produced a dose-dependent inhibition of histamine release from human colonic mucosal and muscle mast cells stimulated with anti-IgE. The IC30 values were in the range 0.5-10 microM and the maximum inhibition approached 50%. The compounds showed similar efficacy against rat peritoneal mast cells but were more potent. The cytoprotectant misoprostol had a striking effect on the human colonic mast cells, producing more than 50% inhibition at concentrations of 0.1-1 nM, but was much less active against the rat cells.

Animals↗