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Biomedical subjects

P A Sylvester

Publications and source records attributed to P A Sylvester.

16 recordsLinked to original sources
PubMed2005

Fast-track barium enema: meeting the two-week wait rule for patients with suspected colorectal cancer.

OBJECTIVES: To meet the introduction of the two-week wait (TWW) rule for patients with suspected colorectal cancer, a fast-track barium enema (FTBE) service was set up. This study was conducted to evaluate the success of this approach in preparation for meeting the forthcoming targets on waiting times to treatment from referral and diagnosis. METHODS: All patients were offered a double-contrast barium enema within two-weeks, except those with a palpable rectal mass. FTBE were double-reported by specialist gastrointestinal radiologists. Patients with a suspected malignancy were booked for an urgent staging CT and outpatient appointment, whilst the remaining patients were referred back to their general practitioner with a report. Prospective data were collected and two 16-month periods analysed. RESULTS: Three hundred and nine patients had a FTBE over the first 16-month period and 277 (89.6%) were seen within two-weeks. Mean times from initial referral to staging CT and first outpatient appointment were 30.7 and 36.0 days, respectively. Cancer was confirmed histologically in 32 (10.4%) patients. Of 267 patients without a malignancy, 46 (17.2%) were referred back to the colorectal outpatient or endoscopy service within 6-months. The number of referrals increased with time from a mean of 19.3 per month in the first period to 27.8 in the second, but the percentage with a suspected malignancy remained similar at 13.6% and 10.1%, respectively. CONCLUSION: FTBE diagnosed malignancy accurately and facilitated rapid staging. The TWW target was met in almost 90% of patients, whilst the impact on the colorectal outpatient and endoscopy service was minimized.

Aged↗
PubMed2005

Pulmonary staging in colorectal cancer--is computerised tomography the answer?

INTRODUCTION: Pulmonary staging in colorectal cancer (CRC) has traditionally been carried out by means of plain chest radiograph (CXR), although computerised tomography (CT) imaging of the chest is increasingly being performed for this purpose. The aim of this study was to assess the value of pre-operative thoracic CT for pulmonary staging in CRC. PATIENTS AND METHODS: Data were collected prospectively on all patients referred into hospital over a 20-month study period for double contrast barium enema evaluation of symptoms suggestive of an underlying CRC. Patients with a CRC went on to have a staging intravenous, contrast-enhanced CT of the chest, abdomen and pelvis prior to an out-patient appointment with a colorectal surgeon. The CXRs of those patients in whom a radiological abnormality was seen on thoracic CT were reviewed blindly by an independent consultant radiologist. RESULTS: A total of 403 barium enemas were performed, of which 38 demonstrated a CRC (9%). In those patients diagnosed with CRC, nine (24%) had an abnormality on thoracic CT. Four patients with positive thoracic CTs had chemotherapy and or radiotherapy with no surgery. One patient underwent colectomy, and 2 patients who had primary lung tumours as opposed to metastases also underwent colectomies. One patient received palliative care only. In addition, one of the patients underwent multiple, non-diagnostic thoracic investigations prior to a diagnosis of sarcoidosis being made and then proceeding to surgery. An independent consultant radiologist reviewed seven out of the nine CXRs of patients with an abnormality on thoracic CT without knowledge of the clinical diagnosis, and reported three of the CXRs to be normal. CONCLUSIONS: Thoracic CT appears to improve the accuracy of pulmonary staging in CRC allowing a more appropriate level of intervention. However, CT is likely to identify more benign radiological abnormalities than CXR alone, and investigations should not occur to the detriment of treating the primary tumour.

Aged↗
PubMed2002

Mucin gene expression in the ileoanal reservoir is altered and may be relevant to the risk of inflammation and dysplasia.

BACKGROUND: Adaptive colonic phenotypic change of the ileal mucosa is a feature of the ileoanal reservoir (IAR) with time, as described by mucin glycoprotein and histological analysis. Mucin gene expression is altered in colorectal neoplasia and inflammatory bowel disease but little is known of its expression in the IAR. AIMS: To examine the changes in mucin gene expression contributing to mucosal protection of the IAR against a background of known changes occurring in inflammatory disease and colorectal neoplasia. PATIENTS: Paraffin embedded specimens from 29 "W" and 11 "J" ileoanal reservoirs were studied. Colonic and ileal control tissue was obtained from normal resection margins. METHODS: Mucin mRNA was detected by in situ hybridisation using [(35)S]dATP labelled oligonucleotide probes. Mucin core protein was detected by immunohistochemistry. RESULTS: There was no change in mRNA expression of MUC1-4 in the IAR compared with ileal controls but there was a decrease in the protein product of MUC1 and MUC3. No mRNA transcripts of MUC5AC, 5B, or 6 were detected but protein product of MUC5AC and MUC6 was detected. Both cases of MUC6 positivity and 1/5 cases of MUC5AC positivity were confined to the ulcer associated cell lineage. No dysplasia was detected. CONCLUSIONS: There is a change in the pattern of the membrane associated mucins MUC1 and MUC3, part of which is in keeping with changes described in colorectal neoplasia. A small number of cases demonstrated mucin gene changes (MUC5AC) which are seen in early neoplasia and this may provide a valuable monitor for such changes in IAR surveillance.

Child↗
PubMed2001

Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials.

OBJECTIVE: To determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes. DESIGN: Systematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials. MAIN OUTCOME MEASURES: Anastomotic dehiscence, infection of any type, wound infection, pneumonia, intra-abdominal abscess, length of hospital stay, and mortality. RESULTS: Eleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046). CONCLUSIONS: There seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.

Anastomosis, Surgical↗
PubMed2001

Differential expression of the chromosome 11 mucin genes in colorectal cancer.

The four secretory mucin genes clustered on chromosome 11, MUC2, MUC5AC, MUC5B and MUC6, were screened in 37 patients with cancers in the left hemi-colon or rectum and 10 normal rectal controls. The mucin genes were detected by in situ hybridization using oligonucleotide probes to the variable number tandem repeat (VNTR) sequences, while the proteins were stained with non-VNTR (MUC2, MUC5AC and MUC5B) or VNTR (MUC6) antibodies. Low levels of MUC2 mRNA were detected in non-mucinous adenocarcinomas (5/27) while a higher proportion of mucinous carcinomas (4/9) was positive. All 25 cases of adjacent normal tissue expressed MUC2 mRNA. No transcripts for MUC5AC, MUC5B or MUC 6 were detected in any of these specimens. MUC2 protein product was detected immunohistochemically in 34/36 carcinoma specimens, with no change from normal controls. There was de novo expression of MUC5AC in 23/36 carcinomas. No MUC5B or MUC6 protein was detected. No difference in MUC2 and MUC5AC protein was found between mucinous and non-mucinous carcinomas. The level of MUC2 was increased in moderately differentiated cancers compared with normal controls and decreased in the poorly differentiated group. Decreased MUC2 was found in poorly differentiated compared with moderately differentiated tumours. More MUC5AC protein was detected in well and moderately differentiated tumours than in poorly differentiated tumours and in all tumours relative to controls. The pattern of MUC2 staining in cancers was different from control tissue, with strong staining in the perinuclear region and none in goblet cell vesicles. MUC5AC staining was mainly detected in the cytoplasm. Poor detection of MUC2 and MUC5AC mRNA and associated strong staining for the total protein suggests altered biosynthesis and processing, leading to the characteristic subcellular distribution. Hence, change in the synthesis of MUC2 and the de novo appearance of MUC5AC in colorectal carcinomas may be significant events in the adenoma-carcinoma sequence, with possible implications for tumour prognosis.

Adenocarcinoma↗
PubMed2000

Coordinated localisation of mucins and trefoil peptides in the ulcer associated cell lineage and the gastrointestinal mucosa.

BACKGROUND AND AIMS: Trefoil factor family (TFF) peptides and the chromosome 11p15.5 mucin glycoproteins are expressed and secreted in a site specific fashion along the length of the gastrointestinal tract. Evidence for coexpression of mucins and trefoil peptides has been suggested in numerous gastrointestinal mucosal pathologies. The ulcer associated cell lineage (UACL) occurs at sites of chronic ulceration in Crohn's disease, expresses all three trefoil peptides, and is implicated in mucosal restitution. We tested the hypothesis that individual trefoil peptides are uniquely localised with specific mucins in the UACL and normal gastrointestinal epithelia. METHODS: Expression of mucin genes in the UACL from small bowel tissue of patients with Crohn's disease was detected by in situ hybridisation, and localisation of the products by immunohistochemistry. Colocalisation of mucins and trefoil peptides was demonstrated by immunofluorescent colabelling in UACL and normal gastrointestinal epithelia. RESULTS: MUC5AC and TFF1 were colocalised in distal ductular and surface elements of the UACL and in foveolar cells of the stomach, whereas MUC6 and TFF2 were colocalised to acinar and proximal ductular structures in the UACL, in the fundus and deep antral glands of the stomach, and in Brunner's glands of the duodenum. MUC5B was found sporadically throughout the UACL and gastric body. MUC2 was absent from the UACL, Brunner's glands, and stomach. MUC2 and TFF3 were colocalised throughout the large and small bowel mucosa. CONCLUSIONS: The UACL has a unique profile of mucin gene expression. Coordinated localisation of trefoil peptides and mucins in UACL and normal gastrointestinal epithelia suggests they may assist each others' functions in protection and repair of gastrointestinal mucosa.

Crohn Disease↗
PubMed2000

Lack of mucin MUC5AC field change expression associated with tubulovillous and villous colorectal adenomas.

BACKGROUND: MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection. AIM: To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence. METHODS: In a prospective cohort study paired mucosal biopsies of adenomatous and macroscopically "normal" mucosa were obtained from 11 patients with villous and 11 patients with tubulovillous adenomas who underwent primary resection for purpose of cure. The tissues were studied to determine MUC5AC gene expression by immunohistochemistry and in situ hybridisation. Patients were followed up by flexible sigmoidoscopy to detect the presence of early local recurrence. RESULTS: 10 villous adenomas showed mature MUC5AC glycoprotein and all 11 expressed MUC5AC mRNA. Five tubulovillous adenomas showed mature MUC5AC glycoprotein and 10 expressed MUC5AC mRNA. Neoexpression of the MUC5AC mucin gene was not detected in any of the mucosal biopsies taken adjacent to either villous or tubulovillous adenomas, even in three patients with early, locally recurrent disease. CONCLUSIONS: Aberrant MUC5AC gene expression is not a "field change" in the colorectal mucosa in patients with rectal adenomas and therefore cannot be used to predict local recurrence of villous and tubulovillous adenomas.

Adenoma, Villous↗
PubMed1999

Vitamin D receptor expression in colorectal cancer.

AIMS: To determine whether the vitamin D receptor is expressed in colorectal cancer, and its relation to stage of disease. METHODS: Paraffin embedded sections of colorectal cancer from 30 patients who had undergone surgery were studied. Immunohistochemistry using the specific monoclonal antibody 9A7 gamma directed against the nuclear vitamin D receptor was used to identify receptors for the active metabolite of vitamin D3 (1,25-dihydroxyvitamin D3). RESULTS: Microscopically normal human colorectal epithelium showed vitamin D receptor expression predominantly in the mid and upper crypts. All the colorectal cancer tissue studied showed vitamin D receptor expression, with a median of 25.3 (range 10.1 to 43.7) cells/graticule field (x 400). Although vitamin D receptor staining was heterogeneous within the individual cancers, neither Dukes stage nor the degree of differentiation appeared to influence expression of the receptor. CONCLUSIONS: Colorectal cancer tissue expresses the nuclear vitamin D receptor and this could act as a potential therapeutic target for synthetic vitamin D3 differentiating agents.

Cell Nucleus↗
PubMed1998

Unacceptably high site variability in postmortem blood alcohol analysis.

Blood alcohol concentration is a frequently requested test in forensic pathology. The variability of this value was studied by measuring the blood alcohol concentration from six sites in nine subjects at necropsy in whom alcohol was the implicated cause of death. There were small consistent differences in the blood alcohol concentrations between the sites in the nine subjects (p < 0.04). Calculation of the mean blood:vitreous humour alcohol concentration ratio (B:V ratio) showed that vitreous humour alcohol concentration most closely reflected the concentration at the femoral vein (B:V ratio = 0.94, r = 0.98), which is considered the optimal site for blood alcohol measurement. The correlation of left heart blood with femoral blood was lower compared with the other sites. There is a potential for an unacceptably large variation in the postmortem measurement of blood alcohol within each subject.

Accidents, Traffic↗
PubMed1997

A comparative audit of prevalent, incident and interval cancers in the Avon breast screening programme.

The 4th year of the Avon breast screening programme comprises two distinct groups: those called for screening for the first time (prevalent group) and those who were initially screened 3 years earlier (incident group). The cancer detection rate, stage of disease and rate of interval cancers in these patients have been compared. For the prevalent groups of year 1 and year 4 there was no statistically significant difference in the cancer detection rate, proportion of small tumours or node positivity. For the prevalent and incident groups of year 4, there was no statistically significant difference in the cancer detection rate or proportion of small tumours. There were significantly fewer node-positive tumours in the incident group (5/45 vs 8/23; P < 0.05). Fifty-six interval cancers presented in the 3-year period between years 1 and 4 of screening; 28 (50%) after 24 months. The screening programme may result in tumours being detected at an earlier stage, but this may be offset by the high rate of interval cancers. This suggests that the time between screens may need to be reduced to 2 years.

Breast Neoplasms↗
PubMed1997

Rate and classification of interval cancers in the breast screening programme.

There has been concern about the number of interval cancers which have been detected within the National Breast Screening Programme. A series of 134 women presenting with interval cancers was studied by prospective audit and the rate and radiological classification of the tumours determined. The cancers were classified as true (67), false-negative (22), unclassifiable (28), occult (12), and minimal sign (5). The interval cancer rate did not achieve the new National Guidelines in either the first 2 years or the 3rd interval year. The false-negative cancers presented mainly in the 1st interval year, whereas the true cancers were predominantly confined to the 2nd and 3rd years. These data suggest that alterations to the screening programme may be beneficial. It may be, however, that the programme is still on the learning curve and this should be taken into account when interpreting these data.

Breast Neoplasms↗
PubMed1995

Tortuosity of the human splenic artery.

Arantius (1571) was the first to describe tortuosity of the splenic artery. The present study investigated the variations in its tortuosity in man, and possible relationships with age, sex, and presence of atheroma. Twenty-nine cadaveric specimens and forty-four celiac angiograms were studied. The straight distance from the origin of the splenic artery, from the celiac trunk, to the point of commencement of the hilar branches was measured, as was the total length of the artery between these two points. The ratio of these two measurements is called the "index of tortuosity." The cadaveric arteries were then opened and graded for the presence of atheroma on a scale of 0 to 3. Marked variation in the index was found in both the cadavers and the angiograms. No definite relationship was found with sex. However, there was a suggestion of increasing tortuosity with age, although in one 10-year-old girl, marked tortuosity was demonstrated on angiography. No significant correlation was shown between increased tortuosity and the extent of atheroma. At present, there is apparently no satisfactory explanation for tortuosity of the splenic artery.

Adolescent↗
PubMed1995

The role of thrombolysis in the management of thromboembolic disorders: a four-year review.

OBJECTIVE: To examine the role of thrombolysis alone, or in conjunction with surgery and angioplasty, in the treatment of thromboembolic disorders. DESIGN: A retrospective review of 70 patients, who received thrombolysis on 73 occasions between 1990 and 1993. PATIENTS AND METHODS: Four groups were defined: (1) thrombolysis alone (40%); (2) thrombolysis followed by angioplasty (23%); (3) thrombolysis followed by surgery (13%) and (4) thrombolysis after failed angioplasty (24%). RESULTS: Twenty-eight patients (40%) received thrombolysis alone of which 13 were successful. In 25 cases (36%) thrombolysis was initially successful in that it permitted further angioplasty or surgical reconstruction. This adjunctive treatment was successful in 16 cases. Overall, when used as a first-line treatment, thrombolysis was successful in 72% of cases. Success in this context includes those in which a further procedure was possible after thrombolysis. These groups included 20 occluded grafts in which thrombolysis played an important part in unblocking 13 (65%) of them. In a separate group of 17 patients (24%) thrombolysis was given after failed angioplasty and was successful on 15 (88%) occasions. Local complications occurred in 17 patients. There were three deaths. There were no intra-cerebral haemorrhages. CONCLUSIONS: Thrombolysis alone can be used successfully. There is a large group in which thrombolysis can help to increase the success rate of interventional radiology.

Adult↗
PubMed1995

Neuropathic urinary retention in the absence of neurological signs.

We present two cases of painless urinary retention secondary to central intervertebral disc prolapse. In neither case were there signs or symptoms suggesting an underlying neurological insult. Both patients voided spontaneously following neurosurgical intervention. The classical features of acute cauda equina compression may be absent in patients with central lumbar disc protrusion. Painless urinary retention may be the only physical sign.

Adolescent↗
PubMedDate not supplied

Abnormal subcellular distribution of mature MUC2 and de novo MUC5AC mucins in adenomas of the rectum: immunohistochemical detection using non-VNTR antibodies to MUC2 and MUC5AC peptide.

Anti-mucin variable number tandem repeat (VNTR) antibodies have been used previously to demonstrate the de novo presence of MUC5AC and MUC6 mucin in colorectal adenomas and increased synthesis of MUC2, the major secreted mucin in normal colorectal mucosa. Here we examined secreted mucins in tubular, tubulovillous and villous adenomas of the rectum using non-VNTR antibodies designed to assess mature mucin. Mucin gene messenger RNAs were detected by in situ hybridization. The anti-MUC2 non-VNTR antibody in the goblet cells of adenomas revealed a staining pattern of increased cytoplasmic, Golgi and membrane staining with no change in goblet vesicle reactivity compared with normal controls. In addition, blank goblet cell vesicle immunostaining for MUC2 was found in the transitional mucosa adjacent to all types of adenoma. Although a trend to overexpression of MUC2 was observed with in situ hybridization this was not detected with immunohistology. De novo synthesis of MUC5AC, but not MUC5B or MUC6 mucin was seen in all adenomas and transitional mucosa using immunohistochemistry. There was no correlation of MUC2 or MUC5AC mucin with polyp size or the grade of dysplasia using the non-VNTR antibodies. This study demonstrates that anti-mucin non-VNTR antibodies reveal a different subcellular-localization in rectal adenomas compared with normal colorectal mucosa. Further, this pattern is in contrast to that reported for anti-mucin VNTR antibodies. Combined use of these reagents may benefit future assessment of these cancers.

Adenoma↗