Effect of flutamide on survival in patients with pancreatic cancer. Results are impressive.
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Biomedical subjects
Publications and source records attributed to O J Garden.
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BACKGROUND/AIMS: Primary graft dysfunction is difficult to predict. We have previously shown that indocyanine green clearance measured at 24 h following orthotopic liver transplantation predicts graft survival and outcome. We prospectively evaluated the use of indocyanine green clearance (with a cut-off value of 200 ml/min) as a marker of graft function following orthotopic liver transplantation and investigated its relationship with the markers of reperfusion injury during orthotopic liver transplantation. METHODS: In all patients indocyanine green clearance was measured at 24 h. Repeated blood samples were taken before, during the anhepatic and reperfusion phase and up to 12 h following orthotopic liver transplantation to measure the levels of neutrophil elastase and reactive oxygen intermediates. All patients studied had normal hepatic arterial pulse on Doppler-ultrasound post orthotopic liver transplantation. RESULTS: All patients with indocyanine green clearance >200 ml/min recovered following orthotopic liver transplantation and remained well up to 3 months of follow up. Four patients had an indocyanine green clearance <200 ml/min; three were re-transplanted for graft failure within 3 days of the transplant, while one survived after prolonged intensive support and hospitalization. Indocyanine green clearance significantly correlated with reactive oxygen intermediates production and neutrophil elastase during orthotopic liver transplantation (r=-0.61, p<0.002 and r=-0.66, p<0.0009, respectively). Indocyanine green clearance was also significantly correlated with alanine aminotransferase and prothrombin time at 24 h post-transplantation (r=-0.35, p<0.02 and r=-0.4, p<0.0077, respectively). CONCLUSION: Indocyanine green reflects the degree of reperfusion injury and is a good early marker of primary graft function. Indocyanine green clearance over 200 ml/min is associated with favorable outcome.
BACKGROUND: The liver plays a central role in ingestive behavior; alterations in metabolic signaling to the brain stem as a result of chronic liver disease could influence intake. OBJECTIVE: We examined the influence of metabolic sequelae of liver disease on nutrient intake and nutritional status. DESIGN: Nutritional status and spontaneous dietary intake were examined in 65 cirrhotic patients and 14 control subjects. The response to feeding was investigated in 14 control subjects and a subgroup of 31 cirrhotic patients. Comparisons were made between patients with primary biliary cirrhosis (PBC) and hepatocellular cirrhosis (HC). RESULTS: Patients were nutritionally depleted. The fasting rate of lipid oxidation in the HC group was greater than in the control group (P < 0.01). In the fasting state, only HC patients were hyperinsulinemic [121.2+/-78.5 compared with 41.3+/-18.6 pmol/L in control subjects (P < 0.001) and 64.7+/-15.8 pmol/L in PBC patients (P < 0.05)] and this persisted during the response to feeding. In the fed state, the magnitude of change in carbohydrate oxidation was greatest in the HC group (HC: 34.6%; control: 23.1%; PBC: 25.2%). Carbohydrate and energy intakes of the HC group were lower than in control subjects (carbohydrate: 193+/-38.3 compared with 262+/-48.1 g/d, P < 0.05; energy: 6.29+/-1.40 compared with 9.0+/-2.12 MJ/d, P < 0.05). CONCLUSIONS: Reductions in carbohydrate intake could be mediated by hyperinsulinemia and compounded by preferential uptake of carbohydrate. This may enhance gastrointestinal satiety signaling and contribute to hypophagia.
With the recent changes in surgical training and sub-specialisation, the role of surgical trainees in more advanced surgical procedures has come into question. In order to examine this further, we analysed the early outcome of patients in a single surgical unit undergoing pancreatic resections, with regard to the grade of the surgeon performing the operation. Between January 1994 and May 1996, data were collected prospectively on all the patients undergoing pancreatic resections with regards to the grade of the surgeon performing the procedure and the early outcome following the operation. Sixty-two patients underwent pancreatic resections for both benign and malignant diseases. Overall, 19 operations (31%) were performed by trainees under supervision, 14 of the 40 pancreatico-duodenectomies (35%) and 5 of the 19 left partial pancreatectomies (26%). All 3 total pancreatectomies were carried out by consultants. In the 43 patients operated upon by the consultants, there were 8 anastomotic leaks (19%) and 1 death. In the 19 patients operated upon by the supervised trainees, there were only 2 anastomotic leaks (11%) and no deaths. This series has demonstrated that in a unit with a major interest and large workload in pancreatic surgery, there appears to be no difference between a consultant and a supervised trainee in the early outcome following pancreatic resections.
The influence of crossmatching in liver transplantation is still controversial, and at present, our unit does not alter management according to the result of standard lymphocytotoxicity testing. This study retrospectively assessed outcome of grafts transplanted in the presence of preformed antidonor cytotoxic antibody. One hundred twelve patients undergoing their first orthotopic liver transplantation had results available (mean follow-up: 18 months). Twelve patients had a positive crossmatch and 100 negative. The 1-year graft survival was 58% in the positive crossmatch group, compared with 81% in the negative crossmatch group (P = .02). The 1-year patient survival was 83% in the positive crossmatch group compared with 90% in the negative group (P = .41). Acute cellular rejection occurred in 6 of 7 (86%) grafts surviving more than 7 days in the positive crossmatch group compared with 46 of 88 (52%) grafts in the negative group (P = .09). However, episodes of further acute cellular rejection requiring treatment occurred in 4 of the 6 grafts in the positive crossmatch group but in only 4 of the 46 grafts with a negative crossmatch (P = .0006). The authors conclude that evidence exists in our population that preformed antidonor antibodies adversely affect the outcome of hepatic allografts but not patient survival.
BACKGROUND: Most reports highlighting decreasing operative morbidity and mortality rates following hepatic resection have focused on the management of metastatic disease. Information on the full range of hepatic disease is lacking. METHODS: The indications for hepatic resection in a specialist hepatobiliary unit have been reviewed and the operative morbidity and mortality rates assessed. RESULTS: Among 129 patients undergoing 133 hepatic resections between October 1988 and September 1996, the principal indication for resection was hepatic malignancy (102 resections), metastatic in 66 cases. Other indications included contiguous tumour (n = 20), primary tumour (n = 16) and benign disease (n = 31). Some 116 procedures were classical anatomical resections. Blood transfusion was required in 40 per cent of cases but major morbidity occurred in 20 per cent. There were six deaths following surgery, five of which were due to hepatic failure and followed resection for malignancy or trauma. The 3-year survival rate in patients resected for colorectal metastases was 65 per cent. CONCLUSION: This experience has demonstrated an increasing role for hepatic resection in a wide variety of hepatobiliary pathologies. Despite the low postoperative mortality rate, the significant risk of complications in the postoperative period serves to emphasize the need for careful selection of patients for such surgery, which should be undertaken in specialist centres.
BACKGROUND: Cystic pancreatic tumours may be misdiagnosed as pseudocysts. METHODS: From August 1990 to January 1998, 21 patients (16 women) with a median age of 60 years underwent operation for a cystic mass in the pancreas with histological confirmation of neoplasia (six serous cystadenoma (SCA), three mucinous cystic adenoma (MCA), ten mucinous cystadenocarcinoma (MCAC), one ductal adenocarcinoma with cystic degeneration, one cystic islet cell tumour). RESULTS: While the lesion had been labelled as a pseudocyst in eight patients, only one patient (MCA in the pancreatic head) had had acute pancreatitis previously. In seven patients the computed tomogram (CT) lacked suspicious neoplastic features, while endoscopic retrograde cholangiopancreatography, angiography and percutaneous cyst fluid analysis were unhelpful or misleading in 16 of 18 investigations with respect to differentiating tumour from pseudocyst. Attempted operation for cure was performed in 18 patients despite diagnostic delays of up to 6 years and initial treatment with cystenterostomy in two cases. CONCLUSION: Retrospective review revealed that all 21 cystic neoplasms could be diagnosed before operation by a history excluding previous pancreatitis (20 of 21 patients) or a CT suspicious for neoplasia (14 of 21). The diagnosis relies more on absence of previous pancreatitis and a suspicious clinician who errs on the side of resecting a pseudocyst rather than watching or draining a cystic neoplasm.
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We have documented the changes in gas exchange, haemodynamic state and associated physiological variables which occurred after graft reperfusion in 20 patients undergoing uncomplicated orthotopic liver transplantation. Gas exchange was measured during constant ventilation using a metabolic monitor. After reperfusion, there were increases in VO2 (mean increase 57 (SD 25) ml min-1) (P < 0.001), VCO2 (mean increase 38 (17) ml min-1) (P < 0.001) and PaCO2 (mean increase 0.88 (0.56) kPa) (P < 0.001). These were associated with increases in cardiac output (1.2 (1.0) litre min-1 m-2) (P < 0.001) and mean pulmonary artery pressure (9 (6) mm Hg) (P < 0.001). There was a decrease in standard bicarbonate concentration (0.96 (1.6) mmol litre-1) (P < 0.02) and increase in hydrogen ion concentration (8.15 (5.9) mmol litre-1) (P < 0.001) consistent with the release of an acid load from the graft and previously ischaemic tissues. The increases in PaCO2 and hydrogen ion concentration were significantly larger in patients in whom venovenous bypass was used during the anhepatic period compared with the "piggyback" surgical technique. We found correlations between the changes in PaCO2 and VCO2 (r2 = 0.25, P < 0.02), cardiac output and VCO2 (r2 = 0.34, P < 0.01), and cardiac output and VO2 (r2 = 0.34, P < 0.01). We conclude that major alterations in gas exchange occur after reperfusion which result from alterations in metabolic rate and haemodynamic changes. These may be clinically relevant, particularly in patients at risk of cerebral oedema.
OBJECTIVE: To determine the optimal management of symptomatic non-parasitic liver cysts. SUMMARY BACKGROUND DATA: Management options for symptomatic nonparasitic liver cysts lack substantiation through comparative studies with respect to safety and long-term effectiveness. METHODS: A retrospective review of the surgical management of patients with hepatic cysts between October 1988 and August 1997 was undertaken to determine morbidity rates and to assess long-term recurrence. RESULTS: Thirty-eight patients (35 women, 3 men) underwent 48 operations for symptomatic hepatic cysts of mean diameter 12 cm, with a mean follow-up of 41 months. Twenty-three patients had simple cysts, and 15 patients had polycystic liver disease (PCLD). The symptomatic recurrence rates after laparoscopic or open deroofing for simple cysts were 8% and 29%, and for PCLD 71% and 20%, respectively. There were no symptomatic recurrences after 14 hepatic resections. There were no perisurgical deaths; however, morbidity rates were significant after laparoscopic deroofing, open deroofing, and hepatic resection (25%, 36%, and 50%, respectively). CONCLUSIONS: Selection of patients with truly symptomatic hepatic cysts is crucial before considering interventional techniques. For simple cysts, radical laparoscopic deroofing is usually curative; open deroofing should be reserved for cysts inaccessible by laparoscopy. The latter technique is well tolerated; however, long-term symptom control is unpredictable in patients with PCLD. Hepatic resection for PCLD provides satisfactory long-term symptom control but has an appreciable morbidity rate. Although laparoscopic and open deroofing procedures are less reliable in the long term for solitary cysts, they might be useful steps before embarking on this major procedure.
Using case note review, a retrospective analysis was carried out of all patients referred with haemochromatosis and suspected hepatocellular carcinoma between 1988 and 1997 to define the mode of presentation, management and outcome of such patients. All 12 patients were male with a mean age of 67 years. Four patients presented whilst asymptomatic by alpha-fetoprotein screening. Mean time interval between diagnosis of haemochromatosis and hepatocellular carcinoma was 6.7 years. One patient underwent right hepatectomy, seven patients were treated by chemoembolisation and the remaining four patients were treated symptomatically. The median survival of the chemoembolised patients was 13 months. Of those patients treated symptomatically, the median survival was four months. Screening for hepatocellular carcinoma is often not undertaken in patients with haemochromatosis. Survival prospects are poor in patients whose tumour presents symptomatically.
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BACKGROUND: TNM staging of gastroesophageal cancer is improved by the use of laparoscopy for the detection of occult metastases and endoscopic ultrasonography for T and possibly N staging. Laparoscopic ultrasonography may combine the strengths of both of these techniques. The purpose of this study was to compare TNM staging by means of laparoscopic ultrasonography (Lap US), laparoscopy, and conventional computed tomography (CT). METHODS: TNM stage was determined by using Lap US, laparoscopy, and CT scanning in 26 surgical candidates with gastric or esophageal cancer in a blinded fashion. CT scans were also reviewed separately by an expert radiologist. Validation of findings was by means of final pathologic examination. RESULTS: Resectability for potential cure was determined by means of Lap US with a sensitivity of 100% and a specificity of 91% versus 100% and 73% for laparoscopy and 75% and 60% for CT, respectively. Overall TNM staging was 82% accurate for Lap US versus 67% for laparoscopy and 47% for CT (chi-squared, 8.64, p < 0.005, and 10.4, p < 0.005, respectively). Accuracies for Lap US versus laparoscopy versus CT for N stage were 92% versus 84% versus 70%, respectively, for T stage were 92% versus 42% versus 60%, respectively, and for M stage were 89% versus 44% versus 62%, respectively. CONCLUSIONS: T and N staging by Lap US were comparable to published results for endoscopic ultrasonography, and overall TNM staging was better. Lap US may provide the optimal preoperative staging for gastric cancer and has the potential to complement endoscopic ultrasonography in staging esophageal cancer.
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The geographical prevalence varies considerably in different countries and Scotland is regarded as an area of low risk for the disease. AIMS: To assess the association between chronic hepatitis C infection (HCV) and HCC in a population of patients presenting to a single hospital. PATIENTS: One hundred and fourteen cases of histologically confirmed liver cancer presenting to the Royal Infirmary of Edinburgh between 1985 and 1994 were examined. METHODS: Of 114 cases of HCC, 80 samples of stored sera were available. Samples positive for HCV Ab were genotyped by restriction fragment length polymorphism analysis of HCV c-DNA. A population of 29 cirrhotic patients (diagnosed between 1985 and 1994) with chronic HCV infection was also genotyped. RESULTS: Chronic HCV infection was a major risk factor (30% of tested HCC patients) identified. HCV genotype 1b was predominant (16 of 20 patients). The time from HCV transmission to development of cancer ranged from 10 to 50 years (median 30). In the cirrhotic patient population, a broader distribution of genotypes was present (genotype 1a: 7; genotype 1b: 8; genotype 2b: 3; genotype 3a: 8 and genotype 4: 2). However, this population was significantly younger. (Mean (SD) 52 (14.5) years) (p = 0.0002) and demonstrated a significantly shorter duration of infection: range 10-40 years (median: 19). CONCLUSION: There is a strong association between chronic HCV infection, cirrhosis, and hepatocarcinogenesis in this Scottish population. The study was unable to distinguish whether the high prevalence of genotype 1b in the HCC population reflected increased oncogenicity in itself, or whether 1b was simply the most prevalent genotype in Scotland when these patients were infected.
We present a case of recurrent variceal bleeding due to subtotal occlusion of the splenoportal junction by a pancreatic carcinoma. This was effectively treated by transhepatic venous angioplasty and stenting.
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