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Biomedical subjects

A R Dennison

Publications and source records attributed to A R Dennison.

At least 37 records · Page 2Linked to original sources
PubMed2002

The mystery of liver regeneration.

BACKGROUND: Partial hepatectomy is the strongest stimulator of hepatic regeneration. The process of initiation and the control of the final size of the regenerated liver have been the subject of research for many years. A better understanding of this process and the effect of disease may allow better selection of patients for partial hepatectomy. It may also allow an insight into the possible application of clinical stimulation of regeneration. METHODS: Data were reviewed from the published literature using the Medline database. RESULTS: Most knowledge comes from in vitro studies and the study of resection in the rat model. A variety of cytokines, hormones and growth factors are involved in regeneration but very few have been found capable of stimulating regeneration in vitro. The exact interactions are not known, but there is probably a cascade involving different factors at differing stages of regeneration. CONCLUSION: Further in vivo research should allow greater understanding of liver regeneration, thereby providing a potential therapeutic tool in patients for whom regeneration has failed, or is likely to fail. Such research is also important in respect of liver support devices, which may inhibit liver regeneration by filtration of many of the factors involved.

Cytokines↗
PubMed2002

Idiopathic chronic ulcerative enteritis--the role of radical surgical resection.

Idiopathic chronic ulcerative enteritis is uncommon. It is a term that describes ulceration of the small bowel in the absence of a recognisable cause. Patients mainly present with a surgical abdomen and their management often proves to be a therapeutic challenge. Our series describes three such cases: the first patient presented with a tender left iliac fossa mass and rectal bleeding, the second with peritonitis and pneumoperitoneum, the third with severe acute colitis. All three patients needed urgent surgical intervention with further laparotomies due to recurrent ulceration, perforation and fistula formation in addition to intensive supportive measures such as inotropes and total parenteral nutrition. The importance and challenges of idiopathic chronic ulcerative enteritis are therefore discussed.

Adult↗
PubMed2001

Pancreas resection and islet autotransplantation for end-stage chronic pancreatitis.

OBJECTIVE: To assess the safety and efficacy of islet autotransplantation (IAT) combined with total pancreatectomy (TP) to prevent diabetes. SUMMARY BACKGROUND DATA: There have been recent concerns regarding the safety of TP and IAT. This is thought to be related to the infusion of large volumes of unpurified pancreatic digest into the portal vein. Minimizing the volume of islet tissue by purifying the pancreatic digest has not been previously evaluated in terms of the postoperative rate of death and complications, pain relief, and insulin independence. METHOD: During a 54-month period, 24 patients underwent pancreas resection with IAT. Islets were isolated using collagenase and a semiautomated method of pancreas digestion. Where possible, islets were purified on a density gradient and COBE processor. Islets were embolized into the portal vein, within the spleen and portal vein, or within the spleen alone. The total median volume of digest was 9.9 mL. RESULTS: The median number of islets transplanted was 140,419 international islet equivalents per kilogram. The median increase in portal pressure was 8 mmHg. Early complications included duodenal ischemia, a wedge splenic infarct, partial portal vein thrombosis, and splenic vein thrombosis. Intraabdominal adhesions were the main source of long-term problems. Eight patients developed transient insulin independence. Three patients were insulin-independent as of this writing. Patients had significantly decreased insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. Of the patients alive and well as of this writing, four had failed to gain relief of their abdominal pain and were still opiate-dependent. CONCLUSION: Combined TP and IAT can be a safe surgical procedure. Unfortunately, almost all patients were still insulin-dependent, but they had decreased daily insulin requirements and glycosylated hemoglobin levels compared with patients undergoing TP alone. A prospective randomized study is therefore needed to assess the long-term benefit of TP and IAT on diabetic complications.

Adult↗
PubMed2000

Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

BACKGROUND: An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. MATERIALS AND METHODS: A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. RESULTS: No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. CONCLUSIONS: Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors.

Animals↗
PubMed2000

The feasibility of spleen-preserving pancreatectomy for end-stage chronic pancreatitis.

BACKGROUND: It is considered difficult to preserve the spleen at the time of distal or total pancreas resection for chronic pancreatitis (CP). The aim of this study was to assess the feasibility of preserving the spleen in patients requiring total or completion pancreatectomy for CP. METHODS: All patients having total or completion pancreatectomy for CP were evaluated postoperatively in terms of morbidity, mortality, and pain relief. To assess splenic vascularity, all patients underwent abdominal ultrasound and power doppler imaging to assess splenic perfusion and the patency of the remaining splenic vessels. RESULTS: Of 35 patients having total pancreatectomy, the spleen was preserved in 30 patients (19 women, 11 men; median age 40 years). The etiology of CP was mainly idiopathic (n = 14) or alcohol related (n = 12). All patients presented with chronic abdominal pain (median 5 years) requiring opiate-derived analgesia for pain relief. Fifteen patients (50%) had undergone previous therapeutic intervention for pain relief. The spleen was preserved with either an intact splenic artery and vein in 19 patients and or the short gastric vessels (n = 11). The mean duration of the procedure was 7 hours (range 5 to 11) and mean blood loss was 1,090 mL. The 30-day mortality was 3.8% (n = 1). Five patients had splenic complications (17%). These included splenectomy (n = 2), intrasplenic collection (n = 2), and a wedge splenic infarct (n = 1). Two of these complications were related to intrasplenic islet autotransplants. Follow-up with abdominal ultrasound and power doppler scanning showed no other abnormalities; blood flow was demonstrable in all patients with intact splenic arteries and vein (n = 19). The mean hospital stay was 25 days. Of the 24 patients who were beyond 6 months' follow-up, 82% (n = 20) have complete relief of pain, and 4 still require opiate analgesia. CONCLUSIONS: Spleen-preserving pancreatectomy is a feasible procedure for chronic pancreatitis, providing complete pain relief in 80% of patients. When the splenic artery and vein cannot be preserved, there is a minimal risk of splenic complications that may require further treatment; but for the majority of patients, splenectomy is avoided.

Adult↗
PubMed2000

The safety of electrolytically induced hepatic necrosis in a pig model.

BACKGROUND: Electrolysis fulfils the criteria for an ideal treatment of patients with unresectable liver tumours. Previous studies in the rat and pig have shown that controlled necrosis can be safely produced by inserting platinum electrodes into normal liver' parenchyma and liver tumours. As with any new treatment it is mandatory to investigate the 'worst-case scenario' of inadvertent intravascular electrode placement in a large animal model before progressing to clinical trials. METHODS: Under ultrasound control in six pigs, electrodes were inserted into, or immediately adjacent to, an hepatic vein. An electrolytic 'dose' of 100 C was then administered and the evolution of the lesion was monitored using ultrasound. Venous blood was collected before and during the electrolysis to evaluate potential acid/base disturbances and animals were closely monitored during electrolysis and during their recovery until a full autopsy was performed 4-7 days after treatment. RESULTS: Gas bubbles were seen to enter the hepatic veins or interior vena cava during treatment in five of the six animals. There were no major complications as a consequence and all animals recovered and remained in a healthy state until they were killed. At autopsy one animal had complete thrombotic occlusion of the left hepatic vein. Otherwise, findings were normal. CONCLUSION: In the clinical setting, due to the use of ultrasound to guide electrode placement into the centre of a tumour, the electrodes should rarely juxtapose an hepatic vein. Nevertheless, in this extreme situation, electrolysis is surprisingly safe with only one major vascular occlusion and no morbidity or mortality.

Animals↗
PubMed2000

Electrolytic treatment of colorectal liver tumour deposits in a rat model: a technique with potential for patients with unresectable liver tumours.

BACKGROUND/AIMS: Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver 'metastases' in the rat. METHODS: Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. RESULTS: Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. CONCLUSIONS: This study has shown that colorectal liver 'metastasis' can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a 'secondary' ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.

Adenocarcinoma↗
PubMed2000

Intrahepatic biliary cystadenoma causing luminal common bile duct obstruction.

BACKGROUND: Biliary cystadenomas are rare cystic tumours that arise in the liver or less frequently in the extrahepatic biliary system. They are commoner in middle-aged women, their most favoured site is the right hepatic lobe. METHODS: Case report and review of the literature. RESULTS: We present only the second case of an intrahepatic cystadenoma causing luminal obstruction of the common bile duct. Clinical presentation is often non-specific and can prove to be a diagnostic challenge. CONCLUSION: Wide local excision of biliary cystadenomas is recommended, with regular radiological follow-up.

Adenoma, Bile Duct↗
PubMed2000

Human islet autotransplantation to prevent diabetes after pancreas resection.

In severe cases of chronic pancreatitis pain relief can often only be achieved by pancreas resection, however this may render the patient diabetic. In an effort to prevent diabetes some patients may be suitable for a simultaneous islet autotransplant. The last report from the International Islet Transplant Registry has reported 222 cases. This review discusses the current progress in human islet autotransplantation.

Chronic Disease↗
PubMed2000

Electrolytic ablation of colorectal liver metastases: 1-year histological patient follow-up.

Whilst up to 50% of patients with colorectal carcinoma will develop liver metastases, only 20% of those patients will be amenable to potentially curative liver resection. There is therefore great need for other effective therapies, and we report complete ablation of a colorectal liver metastasis using electrolysis, which was histologically confirmed at 1 year. The clinical impact of complete tumour ablation at 1 year means that a proportion of those patients currently deemed inoperable and therefore incurable, may be suitable for curative treatment.

Adenocarcinoma↗
PubMed2000

Experience of combined endoscopic percutaneous stenting with ultrasound guidance for drainage of pancreatic pseudocycts.

The therapeutic options for treatment of pancreatic pseudocysts are numerous. We report our experience of combined endoscopic and ultrasound guided percutaneous stenting for pancreatic pseudocysts. Data were prospectively collected for 20 consecutive patients. All patients had undergone a standard technique of combined endoscopic and ultrasound guided percutaneous placement of double J stents, between a pancreatic pseudocyst and the stomach. Patients age ranged between 25 and 84 years. Thirteen of the pseudocysts were due to acute pancreatitis and 7 were due to chronic pancreatitis. The duration of the combined procedure was mean 50 min (range 30-95 min). The length of hospital stay was mean 5 days (range 2-77 days. Only two patients suffered postoperative complications; one was re-admitted 2 weeks following stenting with acute cholecystitis, the other suffering a perforated duodenal ulcer 3 weeks after stenting. There were two failures early in the series, both due to stent migration, these stents were of a small size, (4.7 French). Following this the stent size was increased to at least 7 French, no further failures occurred. There was no operative mortality for the series. Follow-up ranged between 6 months and 5 years. We conclude that a combined percutaneous and endoscopic cyst-gastrostomy stent is a safe and effective treatment for patients with suitably placed pseudocysts.

Acute Disease↗
PubMed2000

A new treatment for unresectable liver tumours: long-term studies of electrolytic lesions in the pig liver.

The majority of liver tumours are inoperable and an alternative treatment to surgical resection is urgently needed. Electrolysis has been investigated in a rat model and the procedure is safe, with accurate and predictable effects. The necrosis produced has also been shown to cause destruction of tumour deposits in the rat liver. A similar evaluation in a large animal model was necessary before clinical trials could commence. Using platinum electrodes connected to a d.c. generator, areas of hepatic necrosis were created in the pig liver. Animals were killed at various time points after treatment to assess the extent of healing. Treatment was uneventful and all animals made a full recovery. No animal died from the treatment or had to be killed prematurely. After 2 days of treatment, healing was minimal but at successive time points there was progressive evidence of healing, such that after 4 months, the original electrolytic lesion was greatly reduced in size and the large area of necrosis seen at the early time points was largely replaced by a fibrous scar with only small islands of necrotic tissue. In a large animal model, electrolysis is a safe method for creating areas of hepatic necrosis. The lesions heal with time and are associated with minimal morbidity. The results support a trial of electrolysis in patients with unresectable liver tumours.

Animals↗
PubMed1999

Pancreatic islet autotransplantation combined with total pancreatectomy for the treatment of chronic pancreatitis--the Leicester experience.

Islet autotransplantation offers the potential for preventing the surgically induced diabetes that is an inevitable consequence of total pancreatectomy. This paper describes the first islet autotransplant programme in the United Kingdom and the first series in the world to use the spleen as a site for the islet graft. Over an 11 month period, 7 patients underwent total pancreatectomy for chronic pancreatitis combined with a simultaneous islet autotransplant. All 7 patients had normal glucose-tolerance levels and normal C-peptide levels pre-operatively. In 6 patients, islets were embolized into the liver via the portal vein (median transplanted volume=8.5 ml). In addition, 3 patients received islets into the splenic sinusoids via a short gastric vein (median transplanted volume=4 ml). One patient received islets into the spleen alone. One patient died of a stroke 4 weeks post transplantation. Two patients have achieved insulin independence, with a further two patients achieving "transient" insulin independence (<1 month). The remaining 2 patients, although requiring reduced insulin doses, have not achieved insulin-independence. However, all patients have C-peptide levels within the normal range. In trying to explain these findings, split proinsulin levels were measured and found to be elevated. High levels of split proinsulin cross react with the C-peptide assay and this would explain the falsely elevated C-peptide levels. Indeed insulin levels in these patients were all below the normal range. These findings would suggest that the use of C-peptide levels as the "gold standard" for monitoring islet autograft function, may require reappraisal.

C-Peptide↗