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R M Charnley

Publications and source records attributed to R M Charnley.

At least 19 recordsLinked to original sources
PubMed2006

Endoscopic necrosectomy as primary therapy in the management of infected pancreatic necrosis.

BACKGROUND AND STUDY AIMS: Open pancreatic necrosectomy is the standard treatment for infected pancreatic necrosis but is associated with significant morbidity, mortality, and prolonged hospital stay. Percutaneous or endoscopic necrosectomy are alternative techniques. We evaluated the use of endoscopic necrosectomy for treatment of patients with necrosis that could be accessed through the posterior wall of the stomach. PATIENTS AND METHODS: We retrospectively analyzed the indication, patient status according to acute physiology and chronic health evaluation (APACHE) 2 severity score, and success of endoscopic necrosectomy as primary treatment, in selected patients with localized infected pancreatic necrosis, who presented between May 2002 and October 2004. After the necrosis cavity had been accessed, with the assistance of endoscopic ultrasound, a large orifice was created and necrotic debris was removed using endoscopic accessories under radiological control. Follow-up was clinical and radiological. RESULTS: 13 patients (nine men, four women, mean age 53 years), 11 with positive bacteriology, underwent attempted endoscopic necrosectomy. Median APACHE 2 score on presentation was 8 (range 1-18). Four patients needed intensive therapy unit care and one other patient required (nonventilatory) high-dependency unit care only. Necrosis was successfully treated endoscopically in 12 patients, requiring a mean of 4 endoscopic interventions (range 1-10); one patient required open surgery; two underwent additional percutaneous necrosectomy and one required laparoscopic drainage. Two patients died of complications unrelated to the procedure. The 11 survivors have a median (range) follow-up of 16 (6-38) months. CONCLUSION: Endoscopic necrosectomy is a safe method for treatment of infected pancreatic necrosis. Multiple procedures are usually needed. It may be combined with other methods of surgical intervention. Larger prospective studies will more precisely define its role.

Adult↗
PubMed2005

Management of hilar cholangiocarcinoma in the North of England: pathology, treatment, and outcome.

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center. METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152 percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these, 36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05). Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions. CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality. Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.

Adult↗
PubMed2003

Heteroplasmic ratio of the A3243G mitochondrial DNA mutation in single pancreatic beta cells.

AIMS/HYPOTHESIS: To examine whether there is a high content of mutated mitochondrial DNA in individual pancreatic beta cells from a patient with the A3243G mitochondrial DNA mutation. METHODS: Tissues were available from a patient with diabetes and the A3243G mutation including pancreatic tissue. We quantified the amount of mutated mitochondrial DNA in tissue homogenates and single pancreatic beta cells using hot last cycle PCR. RESULTS: The percentage ratio of mutated to wild-type mtDNA was high in tissues such as muscle and brain (>60%), but surprisingly low in both pancreatic islets and in individual beta cells from these islets. The islets were smaller in the patient than in control subjects in keeping with a decreased beta-cell mass. CONCLUSIONS/INTERPRETATION: These observations suggest that either the beta cells show increased sensitivity to the effects mtDNA mutations on respiratory chain function, and/or cells with a high mutant load are preferentially removed leading to a progressive decrease in the islet beta-cell mass.

Brain↗
PubMed2002

T cell adhesion and cytolysis of pancreatic cancer cells: a role for E-cadherin in immunotherapy?

Pancreatic cancer is an aggressive and potent disease, which is largely resistant to conventional forms of treatment. However, the discovery of antigens associated with pancreatic cancer cells has recently suggested the possibility that immunotherapy might become a specific and effective therapeutic option. T cells within many epithelia, including those of the pancreas, are known to express the alphaEbeta7-integrin adhesion molecule, CD103. The only characterised ligand for CD103 is E-cadherin, an epithelial adhesion molecule which exhibits reduced expression in pancreatic cancer. In our study, CD103 was found to be expressed only by activated T cells following exposure to tumour necrosis factor beta 1, a factor produced by many cancer cells. Significantly, the expression of this integrin was restricted mainly to class I major histocompatibility complex-restricted CD8+ T cells. The human pancreatic cancer cell line Panc-1 was transfected with human E-cadherin in order to generate E-cadherin negative (wild type) and positive (transfected) sub-lines. Using a sensitive flow cytometric adhesion assay it was found that the expression of both CD103 (on T cells) and E-cadherin (on cancer cells) was essential for efficient adhesion of activated T cells to pancreatic cancer cells. This adhesion process was inhibited by the addition of antibodies specific for CD103, thereby demonstrating the importance of the CD103-->E-cadherin interaction for T-cell adhesion. Using a 51Cr-release cytotoxicity assay it was found that CD103 expressing T cells lysed E-cadherin expressing Panc-1 target cells following T cell receptor stimulation; addition of antibodies specific for CD103 significantly reduced this lysis. Furthermore, absence of either CD103 from the T cells or E-cadherin expression from the cancer cells resulted in a significant reduction in cancer cell lysis. Therefore, potentially antigenic pancreatic cancer cells could evade a local anti-cancer immune response in vivo as a consequence of their loss of E-cadherin expression; this phenotypic change may also favour metastasis by reducing homotypic adhesion between adjacent cancer cells. We conclude that effective immunotherapy is likely to require upregulation of E-cadherin expression by pancreatic cancer cells or the development of cytotoxic immune cells that are less dependent on this adhesion molecule for efficient effecter function.

Antigens, CD↗
PubMed2000

Mutations of the cationic trypsinogen gene in patients with hereditary pancreatitis.

BACKGROUND: Hereditary pancreatitis has been shown to be caused by one of two mutations (R117H and N21I) of the cationic trypsinogen gene (PRSS1). Families with hereditary pancreatitis in the north of England were investigated for these mutations. The clinical features associated with each mutation were compared. METHODS: In individuals from nine families with hereditary pancreatitis, DNA was screened for the R117H and N21I mutations. All five exons of the cationic trypsinogen gene were also sequenced to search for additional mutations. Haplotype analysis was carried out to identify common ancestors. Clinical data were collected. RESULTS: The R117H mutation was identified in three families and N21I in a further five. The R117H mutation was associated with a more severe phenotype than N21I in terms of mean(s.d.) age of onset of symptoms (8.4(7.2) versus 16. 5(7.1) years; P = 0.007) and requirement for surgical intervention (eight of 12 versus four of 17 patients respectively; P = 0.029). Haplotype analysis suggested that each mutation had arisen more than once. CONCLUSION: Two mutations in the cationic trypsinogen gene cause hereditary pancreatitis in eight of nine families originating in this region. The R117H mutation is associated with a more severe form of the disease in terms of age at onset of symptoms and requirement for surgical intervention.

Age of Onset↗
PubMed1999

Selection of metastatic tumour phenotypes by host immune systems.

Metastasis and the processes underlying this phenomenon make epithelial cancers so malignant. Local control of cancers by surgery is sometimes possible but locoregional and distant recurrence commonly lead to the failure of treatment with ensuing morbidity and mortality. Tumour cells express a range of new antigens during growth and there are opportunities for the host immune system to interact with these antigens. This immune interaction eliminates the tumour or allows selection of phenotypic variants. Cell phenotypes selected by an incomplete immune response resemble the cell type commonly associated with metastases. Thus we propose that the host immune system may be responsible for selection of this phenotype and progression of the disease.

Animals↗
PubMed1999

Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours.

BACKGROUND: Spiral computed tomography (CT) allows high-resolution examination of the pancreas, surrounding vascular structures, lymph nodes and liver. Endoscopic ultrasonography (EUS) also allows high-resolution imaging of the pancreas and adjacent structures but is an invasive procedure. With the availability of spiral CT, the role of EUS in the investigation of patients with suspected pancreatic or ampullary tumours is unclear. METHODS: Forty-eight patients with clinical suspicion of a pancreatic or ampullary tumour underwent both spiral CT and EUS. Thirty-four patients had surgical exploration, of whom 17 underwent pancreatic resection and 17 had biliary and gastric bypass. The results of spiral CT and EUS were compared with the operative findings. RESULTS: The final histological diagnosis was ductal adenocarcinoma (24 patients), ampullary carcinoma (six), serous cystadenoma (two) and chronic pancreatitis (two). EUS demonstrated 33 and spiral CT 26 of the 34 primary lesions. EUS was particularly useful in the assessment of small resectable tumours missed by spiral CT. The sensitivity and specificity of EUS and spiral CT for detecting involvement by the tumour of the superior mesenteric vein, portal vein and lymph nodes were similar, but EUS was less effective at evaluating the superior mesenteric artery. CONCLUSION: EUS is an important additional investigation after spiral CT in patients with a suspected pancreatic or ampullary tumour.

Adult↗
PubMed1999

Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case-control studies.

BACKGROUND: It has been hypothesized that the cirrhotic liver is afforded protection against metastasis. The evidence has been examined and the plausibility of such a phenomenon is reviewed. METHODS: A systematic literature review was conducted with analysis of combined data from post-mortem case-control studies. RESULTS: Overall, the crude rate of metastasis to normal liver was 37.3 per cent, while the rate to cirrhotic liver was 23.7 per cent. The Mantel-Haenszel (MH) fixed-effects estimate of the odds ratio was 0. 47 (95 per cent confidence interval (c.i.) 0.41-0.53; chi2 = 136, 11 d.f., P < 0.001). The DerSimonian-Laird (DL) random-effects estimation of the odds ratio was 0.42 (95 per cent c.i. 0.31-0.58; chi2 = 28, 1 d.f., P < 0.001). For tumours arising within the distribution of the portal vein, the crude rate of metastasis to normal liver was 47.6 per cent, whereas the rate to cirrhotic liver was 29.8 per cent. The MH estimate of the odds ratio was 0.45 (95 per cent c.i. 0.37-0.54; chi2 = 68.2, 5 d.f., P < 0.001). The DL pooled odds ratio was 0.44 (95 per cent c.i. 0.28-0.70; chi2 = 12.3, 1 d.f., P < 0.001). The MH and DL pooled estimates of the odds ratio were similar for groups of patients from the East (Japan) and the West (Europe and the USA). CONCLUSION: The post-mortem evidence reviewed suggests that the likelihood of metastasis to the cirrhotic liver is lower than that to normal liver. The degree of protection for tumours arising from within the distribution of the portal vein is neither greater nor less than it is overall. Eastern and Western populations appear to have a similar degree of risk reduction. The differences noted were significant on testing in the meta-analysis, but confounding bias accounting for these differences has not been excluded.

Autopsy↗
PubMed1994

Factors influencing the natural history of colorectal liver metastases.

Palliative treatment of unresectable colorectal liver metastases is common and often justified with reference to historical data on the natural history of the disease. However, in view of the improved diagnostic accuracy of modern imaging techniques, these previously published series do not provide sufficient guidance to judge the prognostic efficacy of palliative treatment. In the late 1970s we started prospectively to collect data on consecutive patients with colorectal liver metastases according to a standard protocol. We now present data derived from this series on factors that may affect outcome in untreated patients. Between January, 1980, and December, 1990, 1099 consecutive patients were recorded, of whom 566 (51.5%) received no treatment for their hepatic tumour. Excluding 34 early deaths and 48 patients with a second malignant tumour, 484 patients provided the basis for analysis. All patients were followed up to July 1, 1993, or death. At the closing date of the study only 1 untreated patient was still alive. The impact of various factors on survival was analysed by univariate and multivariate analyses. Six independent determinants of survival were identified in the following order: percentage liver volume replaced by tumour (LVRT), grade of malignancy of the primary tumour, presence of extrahepatic disease, mesenteric lymph-node involvement, serum carcino-embryonic antigen, and age. The subsequent combination of the independently significant factors, separately for patients with up to or more than 25% LVRT, yielded a prognostic tree that displayed median survival times of various subgroups of 3.8 to 21.3 months. These findings provide a framework to estimate the survival expectancy of untreated patients, thereby allowing improved assessment of the prognostic significance of palliative therapeutic approaches.

Colorectal Neoplasms↗
PubMed1993

A case of bilateral trench foot.

A case of severe bilateral trench foot is presented in a patient who lived rough for 3 weeks without removing his boots. Non-operative management yielded no clinical improvement and bilateral below-knee amputation was necessary. Histology revealed subcutaneous and muscle necrosis with secondary arterial thrombosis.

Adult↗