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Biomedical subjects

A K Siriwardena

Publications and source records attributed to A K Siriwardena.

At least 19 recordsLinked to original sources
PubMed2006

Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer.

BACKGROUND: Although many biochemical markers have been examined in pancreatic cancer none are definitive for pre-operative diagnosis. This systematic review examines studies using biochemical markers for the diagnosis of pancreatic cancer in order to appraise their role in contemporary management algorithms. METHODS: A search of the MEDLINE database was undertaken using the key words pancreatic neoplasm and serum tumour marker. Only studies providing original data on sensitivity and specificity are included and data are presented on diagnostic accuracy, effect of cholestasis and the relation of tumour stage to blood levels of markers. RESULTS: CA 19-9 is the most extensively evaluated with pooled data from 2283 patients. The median sensitivity of CA 19-9 for diagnosis is 79 (70-90%) and median specificity 82 (68-91%). CA 19-9 elevation in non-malignant jaundice results in a fall in specificity. Combination with other markers improves accuracy. CONCLUSION: As the most extensively evaluated marker, CA 19-9 should be used in contemporary algorithms for the diagnosis of pancreatic cancer. Elevated values should be repeated after relief of jaundice.

Biomarkers, Tumor↗
PubMed2006

Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer.

BACKGROUND: Tumour clearance during pancreatectomy may be facilitated by resection of the portal-superior mesenteric vein, but this is associated with increased perioperative risk. There is no consensus about which patients benefit from portal-superior mesenteric vein resection. METHODS: A systematic appraisal was carried out of the literature on portal-superior mesenteric vein resection during pancreatectomy to identify recurrent themes to guide management. A computerized search of the Medline and Embase databases found 52 non-duplicated studies providing relevant data in 1646 patients. Pooled data were examined for information on outcome categories relating to operation, complications, histopathology and overall outcome. RESULTS: The median (range) number of patients with portal-superior mesenteric vein resection per cohort was 23 (4-172). Median operating time was 513 (168-1740) min and blood loss 1750 (300-26000) ml. Postoperative morbidity ranged from 9 to 78 per cent with a median per cohort of 42 per cent. There were 73 perioperative deaths (5.9 per cent of 1235 for whom mortality data were provided). Median survival was 13 months, and 1-, 3- and 5-year survival rates were 50, 16 and 7 per cent respectively. Specimen histopathology confirmed positive nodes in 67.4 per cent. CONCLUSIONS: This is the largest collective report to date on portal-superior mesenteric vein resection in pancreatectomy. The high rate of nodal metastases and low 5-year survival rates suggest that by the time of tumour involvement of the portal vein cure is unlikely, even with radical resection.

Adult↗
PubMed2006

Hyperlipidaemia and outcome in acute pancreatitis.

There is a well-recognised association between hyperlipidaemia and acute pancreatitis. However, the role of hyperlipidaemia in modulating disease course is not clear. The aim of the study was to conduct a prospective study in acute pancreatitis to assess the relation between hyperlipidaemia and disease severity using current disease descriptors. The study population constituted 43 patients with acute pancreatitis, admitted during the calendar year 2001. There were 19 (44%) males. The median (range) age was 50 (21-86) years. Serum triglycerides, cholesterol and high-density lipids were measured on admission. Patients were followed-up for at least 6 months after discharge. Principal outcomes were relation between hyperlipidaemia and peri-pancreatic complications and end-of-episode disease severity. The results showed that hypertriglyceridaemia was present in 14 patients (33%). There was a significant difference in mean (SEM) serum triglyceride levels between patients with alcohol-induced pancreatitis compared with pancreatitis of other aetiologies [3.07 (1.0) mmol/l vs. 1.26 (0.11) mmol/l; p = 0.03, Fisher's exact test]. There was no correlation between admission hypertriglyceridaemia and admission APACHE II score (r(2) = 0.0015). Similarly, there was no correlation between triglyceride level and either pancreatic inflammatory complications or final outcome. In conclusion, this study has demonstrated that there was no significant correlation between hypertriglyceridaemia and either complications of disease or overall end-of-episode severity in this population of patients with acute pancreatitis.

Acute Disease↗
PubMed2005

Intravenous antioxidant modulation of end-organ damage in L-arginine-induced experimental acute pancreatitis.

BACKGROUND: Oxidative stress mediates acinar injury in experimental acute pancreatitis (AP) and antioxidants are depleted in human AP. This study tests the hypothesis that exogenous antioxidant supplementation ameliorates experimental AP. METHODS: Male Sprague-Dawley rats were randomly allocated to 1 of 4 groups (n = 5/group) and sacrificed at 72 h. AP was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/l sodium chloride. Group allocations were: group 1 (control) no intervention; group 2 AP; group 3 early multiple antioxidant (MAOX) intervention comprising 15 microg/kg selenium, 30 microg/kg ascorbate and 300 mg/kg N-acetylcysteine given at 6 and 30 h and group 4 the MAOX combination above given at 24 and 48 h. Endpoints were: serum amylase, antioxidant levels, bronchoalveolar lavage (BAL) protein and lung myeloperoxidase (MPO) activity and histological assessment of pancreatic injury. RESULTS: L-arginine induced AP characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Early MAOX reduced pulmonary MPO and BAL protein and reduced acinar swelling, degranulation and pancreatic parenchymal infiltration by inflammatory cells. These features were absent when intervention was delayed. CONCLUSION: In this model, early but not late antioxidant intervention ameliorates pancreatic and pulmonary injury.

Acetylcysteine↗
PubMed2005

Strategic management of severe acute pancreatitis in the Jehovah's witness.

Haemorrhage can be a lethal complication of severe acute pancreatitis. Management includes identification and control of the source of bleeding and supportive therapy such as blood transfusion. Individuals who refuse transfusion on the grounds of religious belief can provide a further major challenge. The management in these individuals can be focused from the outset with a strategy that aims to avert anaemia and transfusion. This article reports a case of severe acute pancreatitis in a woman of the Jehovah's Witness faith. The episode was complicated by infected pancreatic necrosis requiring surgical intervention. Careful strategic planning is critical to the management of severe acute pancreatitis in patients of the Jehovah's Witness faith. In this case, acute pancreatitis complicated by infected necrosis was successfully managed by the use of preoperative erythropoietin, venesection using paediatric blood vials, meticulous intraoperative attention to haemostasis and the use of adjunctive intraoperative techniques such as argon diathermy.

Adult↗
PubMed2004

Development of procedure-specific patient information sheets for acute abdominal surgery and validation in patients undergoing urgent cholecystectomy or appendicectomy.

This prospective study was carried out in three related phases. In phase I, the information needs perceived by a cohort of 49 patients undergoing urgent abdominal surgery were assessed postoperatively and areas of perceived deficiency identified. In phase II, information provided by consultant surgeons caring for these patients was assessed. This information was then integrated with material gained from insurance companies and governmental organisations on issues such as return to driving in order to generate procedure-specific information sheets for appendicectomy and urgent cholecystectomy. In phase III, these information sheets were validated by a separate cohort undergoing these procedures. Key findings from the patients' perspective were, first, there remains an unmet need for basic information about the impact of urgent abdominal surgery on daily activity. Second, there is a striking variation in the information provided by consultant surgeons. Third, procedure-specific information sheets fulfil an important role in satisfying the patients' information requirements.

Abdomen↗
PubMed2003

A simplified method for computed tomographic estimation of prognosis in acute pancreatitis.

BACKGROUND: Computed tomography is valuable for the diagnosis of acute pancreatitis. Although CT-based prognostic scoring systems are available, they are complex and impractical for routine clinical use. We examined the validity of a simplified CT-based scoring system in a cohort of patients with acute pancreatitis. METHOD: Observational study based on correlation of CT findings with clinical outcomes. Seventy patients admitted to the Royal Infirmary of Edinburgh from January 1991 to December 1997 with a diagnosis of acute pancreatitis and undergoing CT with intravenous contrast during the first 3 to 10 days after admission were included in the study. RESULTS: Multivariate logistic regression analysis demonstrated that the finding of mesenteric oedema and free peritoneal fluid on CT were independent early predictive factors of adverse outcome. Allocating one point each for either mesenteric oedema (MO) or peritoneal fluid (P) (giving a maximum score of 2), a simple MOP score was derived. Compared with the Glasgow and APACHE multiple-factor scoring systems and the Helsinki and Balthazar CT-based scoring systems areas under ROC curves were: admission Apache II 0.57, admission Glasgow 0.62. Balthazar score 0.79, Helsinki score 0.85 and MOP score 0.87. CONCLUSIONS: The presence of mesenteric oedema or peritoneal fluid on CT appears to be a simple and widely applicable predictor of disease severity in acute pancreatitis.

Acute Disease↗
PubMed2003

Intractable pruritus associated with insulinoma in the absence of multiple endocrine neoplasia: a novel paraneoplastic phenomenon.

Insulinoma is a rare tumour, the main symptoms of which are related to hypoglycaemia. Generalized pruritus has been described in association with the multiple endocrine neoplasia syndrome (MEN II or Sipple's syndrome) as a paraneoplastic phenomenon. Further, pruritus is known to be part of the paraneoplastic syndrome in other solid tumours. This case describes a patient presenting with symptoms of Whipple's triad (hypoglycaemic symptoms during fasting, low fasting blood sugar levels and symptoms relieved by intravenous dextrose). Magnetic resonance scanning and selective mesenteric angiography demonstrated a probable pancreatic neuroendocrine tumour. Pituitary fossa imaging and endocrine profile excluded the MEN I syndrome. Symptoms resolved after surgical removal of the tumour. Histology confirmed a pancreatic neuroendocrine tumour. The association between pruritus and insulinoma appears to be a novel paraneoplastic phenomenon.

Female↗
PubMed2003

Intravenous n-acetylcysteine, ascorbic acid and selenium-based anti-oxidant therapy in severe acute pancreatitis.

BACKGROUND: To observe outcome in a cohort of patients with severe acute pancreatitis receiving multiple anti-oxidant therapy. METHODS: An observational study was carried out in 46 consecutive patients with acute pancreatitis fulfilling current Atlanta consensus criteria for severe disease. All patients received multiple anti-oxidant therapy based on intravenous selenium, N-acetylcysteine and ascorbic acid plus beta-carotene and alpha-tocopherol delivered via nasogastric tube. Principal outcomes were the effect of anti-oxidant supplementation on anti-oxidant levels, morbidity and mortality in patients on anti-oxidant therapy, case-control analysis of observed survival compared to predicted survival derived from logistic organ dysfunction score (LODS), logistic regression analysis of factors influencing outcome and side effect profile of anti-oxidant therapy. RESULTS: Paired baseline and post-supplementation data were available for 25 patients and revealed that anti-oxidant supplementation restored vitamin C (P = 0.003) and selenium (P = 0.028) toward normal. In univariate survival analysis, patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 12.6% for each unit increase (95% CI 6.0% to 19.6%). The mean LODS calculated on admission to hospital was 3.7 (standard error of the mean 4.1) giving a predicted mortality for the cohort of 21%. The observed in-hospital mortality was 43%. CONCLUSIONS: Case-control analyses do not appear to demonstrate any benefit from the multiple anti-oxidant combination of selenium, N-acetylcysteine and ascorbic acid in severe acute pancreatitis.

Acetylcysteine↗
PubMed2002

Outcome of necrosectomy in acute pancreatitis: the case for continued vigilance.

BACKGROUND: Surgery for pancreatic necrosis complicating acute severe pancreatitis carries a high risk of mortality and may be influenced by a range of variables including patterns of referral, case selection and quality of care. METHODS: An observational study of a consecutive series of 54 patients undergoing pancreatic necrosectomy in a specialist Hepatobiliary unit over an 8-year study period. Principal outcomes were organ dysfunction and physiological derangement in relation to surgery, microbial colonization of necrosis and relation to outcome, re-operation rates, requirement for peri-operative nutritional support, trends in mortality and survival analysis. RESULTS: Necrosectomy was associated with statistically significant deterioration in immediate postoperative organ dysfunction scores (ANOVA P < 0.01). Infected necrosis was present in 36 (68%). Fungal colonization of necrosis was present in 5 (9%). Mortality in this subgroup was 80% (4 deaths). There was no association between bacterial colonization of necrosis and death in this study (P = 0.77; Fisher exact test; relative risk 0.9,95% confidence interval 0.54-1.54). Twenty patients (37%) required further surgical intervention with an average of 1.5 surgical procedures per patient. Twenty-three patients (43%) died. Patient survival to discharge was best predicted by admission APACHE-II score with relative risk of death increasing 14% for each unit increase in APACHE-II score at admission. CONCLUSIONS: The results of the present study illustrate that there is no place for complacency in the surgical management of patients with severe acute pancreatitis. A clinical governance approach would promote pre-defined protocols between admitting hospitals and tertiary referral centres. Future research should target new interventions in patients with high admission APACHE-II scores in whom prognosis is particularly poor and explore the role of infection of necrotic tissue.

APACHE↗
PubMed2002

Variations in implementation of current national guidelines for the treatment of acute pancreatitis: implications for acute surgical service provision.

OBJECTIVES: The aim of this study was to explore the implementation of the current national guidelines for the treatment of acute pancreatitis. By taking pooled data from all available individual and regional audits, the study aimed to identify areas of consistent variance from the 'best practice' stipulated in the guidelines. METHODS: All published audits of the management of acute pancreatitis where treatment was compared to the current British Society of Gastroenterology guidelines for the treatment of acute pancreatitis were identified from a search of MEDLINE and the published abstracts of relevant specialty meetings. RESULTS: Five audits providing pooled data on 545 patients were identified. Overall mortality from severe disease was 8% (range, 4-17%). Definitive treatment of gallstone disease within 4 weeks of index attack was performed in 49% (range, 16-65%). High dependency or intensive care facilities for severe disease were available in 52% (range, 20-100%). CONCLUSION: This study demonstrates the presence of striking variations in the implementation of the current national guidelines for the treatment of acute pancreatitis.

Acute Disease↗
PubMed2001

Standards of documentation of the surgeon-patient consultation in current surgical practice.

BACKGROUND: This study was designed to assess the reliability of the system whereby junior doctors document the surgeon-patient consultation in general surgical practice in the UK. METHODS: A prospective observational study was carried out, with an independent observer recording details of the surgeon-patient consultation and assessing the reliability of documentation. An exact record of the information given by consultants was transcribed in shorthand at the time of consultation. Data were recorded in the categories recommended for notation by the General Medical Council: clinical findings, decisions made, information given to patient and treatment prescribed. Case notes were examined within 24 h of the ward round to ascertain reliability of the documentation. RESULTS: The study population comprised 432 surgeon-patient consultations. There were important deficiencies in the documentation of consultants' clinical findings and management decisions. In addition, information given by consultants to the patients regarding clinical findings and treatment planned (including the need for operation) was recorded in a median of 6 per cent of consultations. CONCLUSION: This study provides objective evidence of shortfalls in the documentation of the surgeon-patient consultation process. These deficiencies are such that, under present circumstances, the requirements of the General Medical Council with respect to case note documentation are not fulfilled in this setting.

Bias↗
PubMed2001

Evidence against a role for polymorphisms at tumor necrosis factor, interleukin-1 and interleukin-1 receptor antagonist gene loci in the regulation of disease severity in acute pancreatitis.

BACKGROUND: Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and their endogenous antagonists such as IL-1 receptor antagonist (IL-1RA) are important mediators of disease severity in acute pancreatitis. Because the level of secretion of these cytokines is determined in part by genetic factors, the aim of this study was to examine the influence of genetically determined cytokine secretion upon disease severity in acute pancreatitis. METHODS: TNF (TNF-308, TNFB), IL-1beta, and IL-1 receptor antagonist (IL-1RA) genotypes were determined for 190 patients with acute pancreatitis and 102 healthy volunteers. To further assess the influence of genetic factors, the cytokine phenotype for TNF-alpha, IL-1beta, and IL-1RA was determined by using a whole blood culture technique in 51 patients after recovery. RESULTS: The distributions of TNF-308, TNFB, IL-1beta, and IL-1RA gene polymorphisms were similar in patients with mild or severe acute pancreatitis. Further, no difference in gene polymorphism frequencies was observed between patients with acute pancreatitis and healthy controls. With respect to phenotype, the secretion of TNF-alpha was similar in patients with previous mild and severe acute pancreatitis; however, the IL-1beta: IL-1RA ratio was significantly lower in patients with previous severe acute pancreatitis than in those with mild disease. CONCLUSIONS: Our observations suggest that genetic factors are not important in determining TNF-alpha secretion in patients with acute pancreatitis. However, a predetermined imbalance between IL-1beta and its antagonist IL-1RA would appear to exist in patients with severe acute pancreatitis, although the genetic basis for this altered relationship could not be determined.

Acute Disease↗
PubMed2001

Value of angiographic embolisation for the control of major haemorrhage after oesophagogastric or pancreaticobiliary surgery.

OBJECTIVE: To assess the effectiveness of selective mesenteric angiography in finding the bleeding point in patients with haemorrhage after upper gastrointestinal operations, and the efficacy of angiographic haemostasis in controlling haemorrhage. DESIGN: Open study. SETTING: University teaching hospital in the United Kingdom. SUBJECTS: 6 patients who required urgent investigation for haemorrhage after elective oesophagogastric or pancreaticobiliary operations. INTERVENTION: Mesenteric angiography. MAIN OUTCOME MEASURES: Identification of bleeding point and control of haemorrhage. RESULTS: Mesenteric angiograms were done at a median of 20 days (range 3-49) after operation and identified the site of bleeding in all 6 patients. Definitive control of bleeding was achieved by embolisation in 2. Further attempts at angiographic embolisation failed to control the bleeding in the other 4. CONCLUSION: Mesenteric angiography appears to be a valuable investigation in patients with postoperative bleeding after upper gastrointestinal operations. Angiographic embolisation may help to obtain haemostasis, and may stabilise a critically ill patient to allow time for more controlled assessment and treatment.

Adult↗
PubMed2001

Endothelial-derived selectins in the development of organ dysfunction in acute pancreatitis.

OBJECTIVE: The development of organ dysfunction is the principal determinant of outcome in acute pancreatitis and is mediated through a systemic inflammatory response characterized by leukocyte and endothelial cell activation. Up-regulation of the endothelial cell adhesion molecules, E-selectin and P-selectin, is important for endothelial/leukocyte interactions. Levels of serum-soluble E-selectin and P-selectin have been suggested as markers of endothelial activation. This study examines the kinetics of serum-soluble selectins in patients with acute pancreatitis complicated by organ dysfunction. DESIGN: Prospective observational study. SETTING: University teaching hospital with a specialist hepato-pancreatico-biliary service. PATIENTS: Eighteen patients with acute pancreatitis were studied, nine of whom had organ dysfunction. MEASUREMENTS AND MAIN RESULTS: Serial venous blood samples were collected on the first 3 days after admission for measurement of soluble E-selectin and P-selectin by enzyme-linked immunosorbent assay. In all patients, soluble P-selectin concentrations decreased significantly during the study period. Nonsurvivors had significantly higher levels of soluble P-selectin than survivors. In contrast, soluble E-selectin increased significantly during the study period in patients with organ dysfunction, whereas it remained constant in patients without evidence of organ dysfunction. CONCLUSIONS: These results suggest a role for endothelial-derived selectins in the development of organ dysfunction in patients with acute pancreatitis. The observed temporal differences in serum selectin concentrations is in keeping with in vitro observations of endothelial selectin expression.

APACHE↗