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J N Primrose

Publications and source records attributed to J N Primrose.

At least 19 recordsLinked to original sources
PubMed2006

Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies.

No consensus on the indications for surgical resection of colorectal liver metastases exists. This systematic review has been undertaken to assess the published evidence for its efficacy and safety and to identify prognostic factors. Studies were identified by computerised and hand searches of the literature, scanning references and contacting investigators. The outcome measures were overall survival, disease-free survival, postoperative morbidity and mortality, quality of life and cost effectiveness, and a qualitative summary of the trends across all studies was produced. Only 30 of 529 independent studies met all the eligibility criteria for the review, and data on 30-day mortality and morbidity only were included from a further nine studies. The best available evidence came from prospective case series, but only two studies reported outcomes for all patients undergoing surgery. The remainder reported outcomes for selected groups of patients: those undergoing hepatic resection or those undergoing curative resection. Postoperative mortality rates were generally low (median 2.8%). The majority of studies described only serious postoperative morbidity, the most common being bile leak and associated perihepatic abscess. Approximately 30% of patients remained alive 5 years after resection and around two-thirds of these are disease free. The quality of the majority of published papers was poor and ascertaining the benefits of surgical resection of colorectal hepatic metastases is difficult in the absence of randomised trials. However, it is clear that there is group of patients with liver metastases who may become long-term disease-free survivors following hepatic resection. Such survival is rare in apparently comparable patients who do not have surgical treatment. Further work is needed to more accurately define this group of patients and to determine whether the addition of adjuvant treatments results in improved survival.

Colorectal Neoplasms↗
PubMed2005

Ruptured left gastric artery aneurysm successfully treated by thrombin injection: case report and literature review.

Aneurysms of the gastric and gastroepiploic arteries account for only about 4% of all splanchnic artery aneurysms. However, rupture is associated with a mortality of up to 70% and usually warrants urgent surgical intervention. We present an interesting case of a patient who presented with haematemasis following rupture of a left gastric artery aneurysm that was successfully treated by percutaneous thrombin injections. A review of the literature for this rare condition is also presented.

Aneurysm, Ruptured↗
PubMed2003

A randomised clinical trial to assess the effect of total enteral and total parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II > or =6).

BACKGROUND: Total enteral nutrition (TEN) within 48 h of admission has recently been shown to be safe and efficacious as part of the management of severe acute pancreatitis. Our aim was to ascertain the safety of immediate TEN in these patients and the effect of TEN on systemic inflammation, psychological state, oxidative stress, plasma glutamine levels and endotoxaemia. METHODS: Patients admitted with predicted severe acute pancreatitis(APACHE II score >5) were randomised to total enteral (TEN; n = 8) or total parenteral nutrition (TPN; n = 9). Measurements of systemic inflammation (C-reactive protein), fatigue (visual analogue scale), oxidative stress (plasma thiobarbituric acid-reactive substances), plasma glutamine and anti-endotoxin IgG and IgM antibody concentrations were made on admission and repeated on days 3 and 7 thereafter. Clinical progress was monitored using APACHE II score. Organ failure and complications were recorded. RESULTS: All patients tolerated the feeding regime well with few nutrition-related complications. Fatigue improved in both groups but more rapidly in the TEN group. Oxidative stress was high on admission and rose by similar amounts in both groups. Plasma glutamine concentrations did not change significantly in either group. In the TPN group, 3 patients developed respiratory failure and 3 developed non-respiratory single organ failure. There were no such complications in the TEN group. Hospital stay was shorter in the TEN group [7(4-14) vs. 10 (7-26) days; p = 0.05] as was time to passing flatus and time to opening bowels [1 (0-2) vs. 2 (1-5)days; p = 0.01]. The cost of TEN was considerably less than of TPN. CONCLUSION: Immediate institution of nutritional support in the form of TEN is safe in predicted severe acute pancreatitis. It is as safe and as efficacious as TPN and may be beneficial in the clinical course of this disease.

APACHE↗
PubMed2001

Minisatellite instability is found in colorectal tumours with mismatch repair deficiency.

Microsatellite instability (MSI) in colorectal tumours is demonstrated by PCR amplification of several different microsatellite loci. Minisatellites, which are repeats of longer sequences also found throughout the genome, may also be affected by tumorigenesis. Certain minisatellite alleles contain 2 types of similar repeat unit that are randomly interspersed. The interspersion pattern can be analysed by mapping variant repeat units along an amplified allele, minisatellite variant repeat unit mapping PCR (MVR-PCR). We have applied microsatellite analysis with 10 markers and MVR-PCR for locus D7S21 to 33 cases of colorectal neoplasia, 27 sporadic and 6 from patients suspected of having hereditary non-polyposis colorectal cancer (HNPCC). Of the 27 sporadic cases, 3 were MSI-high on microsatellite analysis and one MSI-low. Instability with MVR-PCR was observed, but only in the MSI-high cases. Four of the HNPCC patients had mismatch repair (MMR) gene mutations in either hMLH1 or hMSH2. All 4 had DNA instability by MVR-PCR, but only two of these had MSI (one high, one low). The other 2 of the 6 patients with suspected HNPCC were negative to mutation analysis. One had features strongly suggestive of HNPCC and was unstable by both microsatellite analysis (MSI-high) and by MVR-PCR. The other tumour, from an Amsterdam criteria positive kindred, did not demonstrate instability by any technique. Thus MVR-PCR detects DNA instability in MSI-high sporadic tumours and in those associated with HNPCC where MSI is observed. Further, in some MMR mutation positive cases MSI was not seen but instability was observed by MVR-PCR. MVR-PCR may be a valuable adjunct to the detection of MMR deficiency in colorectal tumours and it may allow new insights into the nature of DNA instability in this condition.

Aged↗
PubMed2001

Cellular resistance to mitomycin C is associated with overexpression of MDR-1 in a urothelial cancer cell line (MGH-U1).

OBJECTIVE: To compare multidrug resistance (MDR)-1 and MDR-3 gene expression in a new urothelial cancer cell line (MGHU-1, with resistance to mitomycin C) against controls and the established (epirubicin-resistant) MDR clone, and to correlate MDR with cytotoxicity data. MATERIALS AND METHODS: Resistance to mitomycin C was induced by the long-term exposure of wild-type MGHU-1 cells to increasing concentrations (20-400 nmol/L) of mitomycin C. The cytotoxicity of mitomycin C or epirubicin was then compared in MGHU-1, MGHU-MMC (mitomycin C-resistant) and MGHU-1R (established MDR) cells, using the tetrazolium biomass assay. The expression of MDR-1 and -3 was investigated by the reverse transcriptase-polymerase chain reaction, using cDNA-specific primers after titration, and compared with DNA and negative controls. RESULTS: MDR-1 and -3 were significantly and equally overexpressed in MGHU-1R, and associated with a dramatic increase in the 50% inhibitory drug concentration (P < 0.001) for mitomycin C and epirubicin against controls. In MGHU-MMC, the overexpression of MDR-1 was three times greater than that of MDR-3. The cytotoxicity profile for both agents was very similar to that of MGHU-1R. Trace amounts of MDR-1, but not MDR-3, were identified in the MGHU-1 wild-type. CONCLUSIONS: Urothelial cancer cell resistance to mitomycin C is associated with cross-resistance to epirubicin and overexpression of MDR-1, suggesting that mitomycin C falls within the MDR category. Clinical application of this methodology may allow patients to be identified who are unlikely to benefit from intravesical chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play a pivotal role in liver fibrosis and stimulating their apoptosis could be an effective treatment for liver fibrosis. METHODS: Activated HSCs, hepatocytes, and rats with liver fibrosis were treated with gliotoxin. RESULTS: Addition of gliotoxin to activated (alpha-smooth muscle actin positive) rat and human HSCs resulted in morphologic alterations typical of apoptosis. Within 2-3 hours of incubation, caspase 3 activity was markedly induced and caspase inhibitor 1 (Z-VAD-FMK)-sensitive oligonucleosome-length DNA fragments were detectable by gel electrophoresis of low molecular weight DNA. Apoptosis was widespread as judged by fluorescence-activated cell sorter analysis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining in both rat and human HSCs at concentrations that had no effect on the viability of rat hepatocytes. Gliotoxin treatment significantly reduced the number of activated stellate cells and mean thickness of bridging fibrotic septae in livers from rats treated with carbon tetrachloride. CONCLUSIONS: These data demonstrate proof-of-concept that by up-regulating HSC apoptosis, the extent of fibrosis can be decreased in inflammatory liver injury.

Animals↗
PubMed2001

Oncofetal fibronectin and oral squamous cell carcinoma.

Fibronectin is a cell matrix glycoprotein, which exists as a number of isoforms that are often found within the cell matrix that surrounds tumours. Collectively these tumour-associated isomers of fibronectin have been termed oncofetal fibronectin (OFFN). We looked for expression of OFFN within oral squamous cell carcinomas (SCC) and related its presence to prognosis. The investigation used a monoclonal antibody (MoAb 5C10) to the glycosylated variant of OFFN, and 100 archival specimens of oral SSC. Immunostaining for OFFN was intense in the adjacent stroma of 43 squamous carcinomas, weak in 27 and absent in 30. Cervical metastases were found in 17/27 (63%) specimens that stained intensely, 6/17 (35%) that stained weakly and 3/13 (23%) that did not stain. Of the 21 cases which had extracapsular lymph node spread, 81% were from those that stained intensely, 19% from those that stained weakly and none from those that did not stain for OFFN expression. Also, 21/44 patients (49%) died in group with intense OFFN staining, 6/26 (23%) in the group with weak staining and 3/30 (10%) in the group that did not stain. The presence of OFFN glycoprotein in oral SCC as evaluated by immunostaining with MoAb 5C10 correlates strongly with the presence of metastatic lymph node involvement, particularly extracapsular involvement, and mortality. We therefore suggest that the degree of expression of OFFN in tumours is a valuable prognostic indicator.

Biomarkers, Tumor↗
PubMed2001

Body composition, physiological function and psychological changes in patients with predicted severe acute pancreatitis.

BACKGROUND: Serious sepsis and major blunt trauma have adverse effects on body composition, physiological function and psychological state. The effect of severe acute pancreatitis on these groups of variables has not yet been reported. METHODS: We have studied the effect of predicted severe acute pancreatitis (admission APACHE II score > or = 6) on body fat and mid arm muscle circumference (assessed by dual-energy X-ray absorptiometry and anthropometry), respiratory function (measured by spirometry and vitalography), voluntary muscle function (measured by hand dynamometry) and psychological state (measured by use of the hospital anxiety and depression score and visual analogue scale for fatigue) on admission, and three and seven days thereafter. RESULTS: The median APACHE II score of the 15 patients (7 men) in this study was 10 (6-13). The patients showed significant improvement in respiratory function (FEV1 1.3, 1.6, 2.3 litres/s, p < 0.01; FVC 1.5, 2.0, 2.9 litres, p < 0.01; PEFR 304, 372, 409 litres/min, p = 0.01 but no change in voluntary muscle function (210, 205, 213 N, p = 0.41) over the 7-day study period. Psychological state improved in terms of fatigue (2.4, 4.2, 7.0, p < 0.01) and depression (6, 9, 4, p = 0.12) but not in anxiety (8, 6, 7, p = 0.07). Body fat measured by DEXA (17.3 kg on admission, 16.7 kg on day 7, p = 0.13) and the mid upper arm muscle circumference (262, 248, 251 mm, p = 0.10) did not change implying that energy and nitrogen balance over the 7-day study period was achieved. CONCLUSION: Predicted severe acute pancreatitis has an adverse effect on respiratory function and psychological state similar to that observed in serious sepsis. Improvement in these variables is apparent over 7 days of effective treatment. Further research is indicated to examine the effect of nutritional support on these variables.

APACHE↗
PubMed2001

Body composition, muscle function and psychological changes in patients undergoing operation for hepatic or pancreatic disease.

BACKGROUND: There is currently a dearth of data with respect to changes in body composition, physiological function and pSychological state in patients undergoing operative treatment for pancreatic or hepatic disease although marked changes in these variables have been reported in colorectal surgical patients. METHODS: In 36 patients (37 operations) we have studied the effect of a pancreatic or hepatic operation (with and without nutritional support) on body fat and body protein (assessed by Dual energy X-ray absorptiometry (DEXA) and anthropometry), respiratory function (measured by spirometry and vitalography), voluntary muscle function (measured by hand dynamometry) and psychological state (measured by use of the hospital anxiety and depression score and visual analogue scale for fatigue) over a 1-week period postoperatively. RESULTS: On the 3rd postoperative day there were significant changes in: grip strength 307 (135-499) to 249 (85-461) N; FEV1 2.28 (0.48-3.98) to 1.02 (0-2.42) litres/min; FVC 2.90 (0.75-5.02) to 1.28 (0.22-3.31) litres; anxiety score 7 (0-17) to 6 (1-20); depression score 3 (0-10) to 5 (0-20), and fatigue 3.9 (0.4-10) to 6.8 (1.0-9.7). These persisted on day 7 by which time mid-arm circumference and total body fat (by DEXA) had fallen from 30.1 (21.1-45.0) to 29.5 (20.2-43.2) cm, and 20.7 (5.8-53.7) to 20.4 (6.6-53.5) kg, respectively. CONCLUSION: We conclude that operative treatment for pancreatic or hepatic disease has an adverse effect on body composition, physiological function and psychological state.

Adipose Tissue↗
PubMed2001

Blind percutaneous insertion of Hickman lines by a specialist team.

BACKGROUND: Long-term intravenous lines for the delivery of chemotherapy can be inserted by the percutaneous route or under direct vision by surgical exploration. Though the percutaneous route is widely used, many centres still employ a surgical approach. This study evaluates the safety of the blind percutaneous approach. METHOD: Prospective records were kept of all Hickman lines inserted on the oncology unit of a large teaching hospital. RESULTS: 127 consecutive lines were inserted in 115 adults by a single surgeon over a 30 month period using a blind percutaneous approach. There were 4 complications of insertion: 2 pneumothoraces (1.6%), 1 arrhythmia (0.8%) and bleeding from the subcutaneous tunnel (0.8%). Only 1 line had to be removed in the first 14 days because of hub fracture and leakage. CONCLUSIONS: Percutaneous insertion of Hickman lines using the blind technique is associated with a low incidence of complications when performed by an experienced operator.

Adult↗
PubMed2000

Bombesin family receptor and ligand gene expression in human colorectal cancer and normal mucosa.

Bombesin-like peptides and their receptors are widely distributed throughout the gut and are potential mitogens for a number of gastrointestinal (GI) cancers. We have analysed the expression of bombesin-like peptides and their receptor subtypes in normal and neoplastic colorectal tissue. Expression was analysed by reverse transcription polymerase chain reaction (RT-PCR) using receptor and ligand subtype-specific primers and then expression localized by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR product. Colorectal cancer tissue and matched normal mucosa from 23 patients were studied. Two of these patients had synchronous adenomatous polyps and two had synchronous hepatic metastases which were also studied. An additional two patients with adenomatous polyps were studied along with matched normal mucosa. Gastrin releasing peptide (GRP) receptor and ligand expression was present in all samples but with overall greater expression in the tumour samples. Neuromedin B (NMB) receptor expression was not detectable. NMB ligand was detected in all but one mucosal sample with overall overexpression in the tumour samples. Bombesin receptor subtype 3 (BRS-3) receptor expression was not detectable. These data support the possibility that GRP may be an autocrine growth factor in colorectal cancer.

Adenocarcinoma↗
PubMed1999

Optimisation of DNA and RNA extraction from archival formalin-fixed tissue.

Archival, formalin-fixed, paraffin-embedded tissue is an invaluable resource for molecular genetic studies but the extraction of high quality nucleic acid may be problematic. We have optimised DNA extraction by comparing 10 protocols, including a commercially available kit and a novel method that utilises a thermal cycler. The thermal cycler and Chelex-100 extraction method yielded DNA capable of amplification by PCR from every block and 61% of sections versus 54% using microwave and Chelex-100, 15% with classical xylene-based extraction and 60% of sections using the kit. Successful RNA extraction was observed, by beta-actin amplification, in 83.7% sections for samples treated by the thermal cycler and Chelex-100 method. Thermal cycler and Chelex-100 extraction of nucleic acid is reliable, quick and inexpensive.

Archives↗
PubMed1999

Marimastat in recurrent colorectal cancer: exploratory evaluation of biological activity by measurement of carcinoembryonic antigen.

Marimastat is a specific inhibitor of matrix metalloproteinases that has been shown to be effective in cancer models. A pilot, escalating-dose study of oral marimastat was performed in patients with recurrent colorectal cancer, in whom evaluation of serological response was made by measurement of carcinoembryonic antigen (CEA) levels. The study assessed the safety and tolerability of 4 weeks administration of marimastat, and determined a dose range producing detectable serological effects. Patients were recruited with a serum CEA level greater than 5 ng ml(-1), and rising by more than 25% over a 4-week screening period. Patients were treated for 28 days and entered into a continuation protocol if a serological response or clinical benefit was observed. Pharmacokinetic and safety data determined that groups of patients were recruited sequentially at 25 mg and 50 mg twice daily, and, thereafter, 10 mg twice daily, 10 mg once daily, 5 mg once daily and 20 mg once daily. A biological effect (BE) was defined as a CEA value on day 28 no greater than on day 0; a partial biological effect (PBE) was defined as a rise in CEA over the 28-day treatment period of less than 25%. Of 70 patients recruited, 63 completed the 28-day treatment period, and 55 were eligible for cancer antigen analysis. Examination of the dose-effect relationships provides evidence for a causal relationship between marimastat and biological effects: the proportion of patients with BE or PBE was higher with twice daily dosing (16 out of 25, 64%) than with once daily dosing (11 out of 30, 37%) (P = 0.043, chi2 test). Furthermore, the median rates of rise of CEA fell markedly during treatment compared with the screening period for patients receiving twice daily marimastat (P<0.0001), but not for patients receiving marimastat once daily (P = 0.25). Musculoskeletal adverse events emerged as the principal drug-related toxicity of marimastat, occurring in a dose- and time-dependent fashion. It was concluded that marimastat was associated with dose-dependent biological effects in cancer patients. The occurrence of musculoskeletal side-effects define 25 mg twice daily as the upper limit of the dose range for continuous use in further studies. Therefore, a dose range of 20 mg once daily to 25 mg twice daily seems appropriate for further studies, which should aim to demonstrate the efficacy of the drug in terms of conventional clinical end points and describe the long-term tolerability of this novel agent.

Administration, Oral↗
PubMed1998

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer.

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.

Adult↗