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Biomedical subjects

R W Parks

Publications and source records attributed to R W Parks.

At least 37 records · Page 2Linked to original sources
PubMed2003

Postchemoembolisation syndrome--tumour necrosis or hepatocyte injury?

Transarterial chemoembolisation of liver tumours is typically followed by elevated body temperature and liver transaminase enzymes. This has often been considered to indicate successful embolisation. The present study questions whether this syndrome reflects damage to tumour cells or to the normal hepatic tissue. The responses to 256 embolisations undertaken in 145 patients subdivided into those with hepatocyte-derived (primary hepatocellular carcinoma) and nonhepatocyte-derived tumours (secondary metastases) were analysed to assess the relative effects of tumour necrosis and damage to normal hepatocytes in each group. Cytolysis, measured by elevated alanine aminotransferase, was detected in 85% of patients, and there was no difference in the abnormalities in liver function tests measured between the two groups. Furthermore, cytolysis was associated with a higher rate of postprocedure symptoms and side effects, and elevated temperature was associated with a worse survival on univariate analysis. Multivariate analysis demonstrated that there was no benefit in terms of survival from having elevated temperature or cytolysis following embolisation. Cytolysis after chemoembolisation is probably due to damage to normal hepatocytes. Temperature changes may reflect tumour necrosis or necrosis of the healthy tissue. There is no evidence that either a postchemoembolisation fever or cytolysis is associated with an enhanced tumour response or improved long-term survival in patients with primary or secondary liver cancer.

Adult↗
PubMed2003

Host immune responses and intestinal permeability in patients with jaundice.

BACKGROUND: Systemic endotoxaemia is implicated in the development of complications associated with obstructive jaundice. The aims of these studies were to assess the systemic immune response to intervention in patients with jaundice and to compare the effects of surgical and non-surgical biliary drainage on host immune function and gut barrier function. METHODS: In the first study, 18 jaundiced and 12 control patients were studied to assess systemic immune responses before and after intervention. In the second study, immune responses and gut barrier function were assessed following surgical and non-operative biliary decompression in 45 patients with jaundice. RESULTS: Endotoxin antibody concentrations fell significantly in patients with jaundice immediately after surgical intervention, but not after non-operative biliary drainage. This decrease was associated with a significant increase in serum P(55) soluble tumour necrosis factor (sTNF) receptor concentration (5.3 versus 10.5 ng/ml; P < 0.001), urinary excretion of P(55) TNF receptors (21.4 versus 78.8 ng/ml; P = 0.002) and intestinal permeability (lactulose : mannitol ratio 0.032 versus 0.082; P = 0.048). Intestinal permeability was significantly increased in patients with jaundice compared with controls (0.033 versus 0.015; P = 0.002). CONCLUSION: These data suggest that obstructive jaundice is associated with impaired gut barrier function and activation of host immune function that is exacerbated by intervention. Surgery causes an exaggerated pathophysiological disturbance not seen with non-operative biliary drainage procedures.

Antibodies↗
PubMed2003

Interstitial ablative techniques for hepatic tumours.

BACKGROUND: Most patients with liver tumours are not suitable for surgery but interstitial ablative techniques may control disease progression and improve survival rates. METHODS: A review was undertaken using Medline of all reported studies of cryoablation, radiofrequency ablation, microwave ablation, interstitial laser photocoagulation, high-intensity focused ultrasound and ethanol ablation of primary liver tumours and hepatic metastases. RESULTS: Although there are no randomized clinical trials, cryoablation, thermal ablation and ethanol ablation have all been shown to be associated with improved palliation in patients with primary and secondary liver cancer. The techniques can be undertaken safely with minimal morbidity and mortality. CONCLUSION: Although surgical resection remains the first line of treatment for selected patients with primary and secondary liver malignancies, interstitial ablative techniques are promising therapies for patients not suitable for hepatic resection or as an adjunct to liver surgery.

Catheter Ablation↗
PubMed2003

Incidence of benign pathology in patients undergoing hepatic resection for suspected malignancy.

BACKGROUND: Confirming the presence of hepatic or proximal bile duct malignancy pre-operatively remains difficult and some patients may undergo surgical resection for suspected malignant lesions which subsequently turn out to be benign. The aim of this study was to establish whether improvements in pre-operative staging might better identify this patient population. METHODS: Analysis of a prospectively collected database, which has been maintained in our unit since 1988. RESULTS: Of 250 consecutive patients undergoing hepatic resection for presumed malignancy, 18 (7.2%) were shown to have benign pathology. These "false positive" rates were 4 out of 160 (2.5%) resections for colorectal metastases, 4 out of 49 (8.2%) resections for other solid hepatobiliary tumours and 10 out of 41 (24.4%) resections for hilar cholangiocarcinoma. Four of the 18 patients (22%) developed post-operative complications but there was no postoperative mortality. CONCLUSION: Although hepatic resection remains a potentially curative procedure for patients with tumours involving the liver parenchyma or proximal bile ducts, pre-operative confirmation of malignancy remains difficult. Despite appropriate investigation a subset of patients with benign disease will still be subjected to major hepatic resection which should be undertaken in a specialist unit.

Adult↗
PubMed2003

Prognostic factors in the palliation of pancreatic cancer.

AIM: Few patients with pancreatic cancer are eligible for resection. In the remainder, estimation of prognosis is important to optimise various aspects of care, including palliation of biliary obstruction and trial of chemotherapy. The aim is to evaluate the prognostic significance of clinical and laboratory variables in patients with unresectable pancreatic cancer. METHODS: Information was gathered retrospectively for 325 patients with unresectable pancreatic cancer who underwent palliative interventions, including surgical bypass, endoscopic or percutaneous stenting or who received supportive care only. RESULTS: Histological proof was obtained in 182 patients (56%). Median survival was 5.7 months. Absence of therapeutic intervention, leukocytosis (WCC> or =11 x 10(9)/l), gamma glutamyl transferase (gamma GT)>165U/L, prothrombin time ratio > or =1.1, and C-reactive protein (CRP) > or = 5mg/dL were associated with shorter survival on univariate analysis. Only absence of therapeutic intervention, leukocytosis, and gamma GT>165 U/L reached significance on multivariate analysis. In the 51 patients in whom serum CRP was available, CRP was the only significant predictor of survival on multivariate analysis. CONCLUSIONS: Leukocytosis, elevated gamma GT and raised CRP predict shorter survival and may help to guide the choice of palliative intervention for patients with unresectable pancreatic cancer.

Aged↗
PubMed2002

Treatment of hepatic metastases of neuroendocrine malignancies: a 10-year experience.

BACKGROUND: Liver metastases from neuroendocrine tumours may give rise to symptoms due to hormone production or mass effect. Accepted management options include administration of somatostatin-analogues, selective chemoembolisation or hepatic resection. The aim of this study was to review the management of hepatic neuroendocrine metastases in our unit. METHODS: Patients with neuroendocrine tumours presenting between 1989 and 1999 were identified from pathology, radiology and surgical databases. Case notes were retrospectively reviewed for demographic data, treatment modality and outcome. Response to treatment was based on biochemistry, radiology or symptoms, and response rates were defined accordingly. RESULTS: Thirty patients with a mean age of 55 years presented with, or later developed liver metastases. The most frequent presenting symptoms were abdominal pain (63%), diarrhoea (40%), weight loss (33%) and flushing (13%). Five patients underwent liver resection with complete symptomatic response, nine underwent chemoembolisation with a 75% response rate (either biochemically, radiologically or symptomatic) and fifteen were treated with a somatostatin-analogue, with a response rate of 86%. Median survival from detection of metastases was 45 months. CONCLUSIONS: Liver resection provides good symptomatic relief, but it is only indicated in a small proportion of patients with metastatic neuroendocrine tumours. Both chemoembolisation and somatostatin-analogues offer useful symptomatic control for these patients with good survival prospects.

Adult↗
PubMed2001

Impairment of Gag-specific CD8(+) T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaques.

The identification of several simian immunodeficiency virus mac251 (SIV(mac251)) cytotoxic T-lymphocyte epitopes recognized by CD8(+) T cells of infected rhesus macaques carrying the Mamu-A*01 molecule and the use of peptide-major histocompatibility complex tetrameric complexes enable the study of the frequency, breadth, functionality, and distribution of virus-specific CD8(+) T cells in the body. To begin to address these issues, we have performed a pilot study to measure the virus-specific CD8(+) and CD4(+) T-cell response in the blood, lymph nodes, spleen, and gastrointestinal lymphoid tissues of eight Mamu-A*01-positive macaques, six of those infected with SIV(mac251) and two infected with the pathogenic simian-human immunodeficiency virus KU2. We focused on the analysis of the response to peptide p11C, C-M (Gag 181), since it was predominant in most tissues of all macaques. Five macaques restricted viral replication effectively, whereas the remaining three failed to control viremia and experienced a progressive loss of CD4(+) T cells. The frequency of the Gag 181 (p11C, C-->M) immunodominant response varied among different tissues of the same animal and in the same tissues from different animals. We found that the functionality of this virus-specific CD8(+) T-cell population could not be assumed based on the ability to specifically bind to the Gag 181 tetramer, particularly in the mucosal tissues of some of the macaques infected by SIV(mac251) that were progressing to disease. Overall, the functionality of CD8(+) tetramer-binding T cells in tissues assessed by either measurement of cytolytic activity or the ability of these cells to produce gamma interferon or tumor necrosis factor alpha was low and was even lower in the mucosal tissue than in blood or spleen of some SIV(mac251)-infected animals that failed to control viremia. The data obtained in this pilot study lead to the hypothesis that disease progression may be associated with loss of virus-specific CD8(+) T-cell function.

Animals↗
PubMed2000

Changes in gastrointestinal morphology associated with obstructive jaundice.

Bacterial translocation has been consistently demonstrated in experimental models of obstructive jaundice. An important factor which promotes this phenomenon is physical injury of the intestinal mucosa. Some previous studies have presented suggestive evidence of this, following bile duct ligation. The aims of this study were to analyse objectively intestinal mucosal morphometric characteristics, to examine for evidence of bacterial translocation, and to assess enterocytes for ultrastructural abnormalities. Adult female Wistar rats were assigned to one of three groups: control (n=8), bile duct ligation (BDL; n=11), or sham operation (n=10). One week later, portal blood, mesenteric lymph nodes, liver, and spleen were harvested and cultured aerobically and anaerobically for evidence of bacterial translocation. Segments of jejunum, ileum, caecum, and large bowel were examined histologically, using light microscopy and morphometrically, using an image analysis system. Electron microscopy was performed on regions of the gastrointestinal tract where significant morphometric alterations had been identified. Significant bacterial translocation was identified following BDL (63. 6% BDL vs. 0% sham vs. 0% control, p<0.01, Fisher's exact test). There was a significant reduction in total mucosal thickness (standard error) [650 microm (23) BDL vs. 731 microm (27) sham vs. 744 microm (95) control] and villous height [451 microm (20) BDL vs. 515 microm (18) sham vs. 559 microm (79) control] in jaundiced animals, compared with sham-operated and control animals (p<0.02, Mann-Whitney U-test). Electron microscopy revealed oedematous change associated with mild inflammation, disruption of desmosomes, and the formation of lateral spaces between enterocytes. In addition, enterocytes showed vacuolation of their cytoplasm and mitochondrial swelling. Increased numbers of bacteria appeared to be attached to the mucosa. These data provide evidence of physical disruption of intestinal mucosa in jaundiced animals, most marked in the distal ileum. Significant bacterial translocation occurs following bile duct ligation and this supports the hypothesis of gut barrier dysfunction with obstructive jaundice.

Animals↗
PubMed2000

Management of pancreatic pseudocysts.

BACKGROUND: This review analyses the outcome for patients with acute and chronic pancreatic pseudocysts managed in two major referral centres. PATIENTS AND METHODS: From 1987 to 1997, 33 patients were treated with either acute (n = 19) or chronic (n = 14) pseudocysts. Procedures performed included cystgastrostomy (64%), cystduodenostomy (6%), cystjejunostomy (3%), distal pancreatectomy with resection of pseudocyst (12%), laparotomy with external drainage (9%), endoscopic transpapillary stenting (3%) and endoscopic pancreatic duct sphincterotomy with percutaneous drainage of the pseudocyst (3%). RESULTS: All patients had resolution of their pseudocyst and no patient developed recurrence. There were no deaths in this series. There was a 9% incidence of major complications and a 21% incidence of minor complications. Outcome was excellent in 63% and good in 27% of patients. Two patients (6%) had persistent chronic pain and one patient (3%) had evidence of exocrine pancreatic insufficiency with malabsorption. CONCLUSIONS: Surgical internal drainage of pancreatic pseudocysts can be performed safely with low morbidity and mortality provided patients are carefully selected and their medical management is optimized. Although minimally invasive techniques now offer a variety of treatment options, open surgical drainage is still indicated for a significant number of cases.

Acute Disease↗
PubMed1999

Management of liver trauma.

BACKGROUND AND METHODS: Management of blunt or penetrating injuries to the liver remains a significant challenge. This review discusses the mechanisms of liver injury, grading system for severity, available diagnostic modalities and current management options. It is based on a Medline literature search and the authors' clinical experience. RESULTS: Unstable patients require immediate laparotomy, but selected patients who are haemo- dynamically stable may be managed without operation. The preferred operative techniques include resectional debridement, hepatotomy with direct suture ligation and perihepatic packing; anatomical resection, hepatic artery ligation and various bypass techniques have a limited, more defined role for selected injuries. Major complications include haemorrhage, sepsis and bile leak. CONCLUSION: Enhanced resuscitation, anaesthesia and intensive care have contributed to a significant reduction in mortality rates from liver trauma. Optimum results are obtained with a specialist team that includes an experienced liver surgeon, anaesthetist, endoscopist and interventional hepatobiliary radiologist with expertise in managing postoperative complications.

Humans↗
PubMed1998

Renal function in jaundiced patients: a prospective analysis.

A prospective analysis was undertaken to assess renal function in patients with obstructive jaundice. A total of 59 jaundiced patients (serum bilirubin > 100 mumol/l) undergoing biliary decompression by surgical, endoscopic or radiological means received prophylactic fluid volume expansion (3 litres crystalloid fluid intravenously) during the 24 hours before intervention. Renal function (urea and electrolytes, creatinine, creatinine clearance, urinary output) was assessed preoperatively and on days 1-7 and on day 28 postoperatively. Two jaundiced patients (3.4%) developed renal failure (urinary output < 400 ml in 24 hours in the presence of an increased serum urea and/or creatinine) and subsequently died. The overall incidence of post-procedural renal impairment (urinary output < 800 ml in 24 hours) was 10.2%. It is concluded that, with vigilant control of fluid and electrolyte balance and pre-procedural intravenous volume expansion, the incidence of renal dysfunction in patients with obstructive jaundice is not as high as previously reported.

Aged↗