An unusual case of ascites: pitfalls in diagnosis of malignant peritoneal mesothelioma.
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Biomedical subjects
Publications and source records attributed to W B Ross.
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BACKGROUND: In patients undergoing liver resection for colorectal liver metastases, a resection edge either involved by tumour or with the tumour extending to within 1 cm is associated with a high risk of liver recurrence and survival is reduced markedly. METHODS: Twenty-six patients underwent cryotherapy of the resection edge following liver resection for metastases from colorectal carcinoma with an involved or inadequate (less than 1 cm) resection margin. RESULTS: At a median follow-up of 23 (range 1-47) months four patients were alive and disease free, and 21 had developed recurrence, of whom 13 had died. One patient died following surgery. Sixteen patients developed recurrences involving the liver, only five of which were at the resection margin. CONCLUSION: Cryotherapy to involved or inadequate resection margins improves local disease control considerably. The use of resection edge cryotherapy might allow a greater proportion of patients with liver metastases to be usefully treated and help to avoid high-risk resections.
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BACKGROUND: Carcinoembryonic antigen (CEA) inhibits lymphocyte function and patients with cancer have lower cell-mediated immunity (CMI) than the normal population. To test this association an investigation was made of the relationship between CMI score, CEA level and survival. METHODS: CEA level, CMI score and other variables were compared with the survival time of 109 patients with colorectal liver metastases using Cox regression analysis. RESULTS: There was a significant association between CMI and CEA categories (P = 0.04, chi 2 test). The odds of patients with normal CMI having a CEA level in the upper quartile observed for all patients were 22 per cent of those of patients with depressed CMI (odds ratio 0.22 (95 per cent confidence interval (c.i.) 0.03-0.90), mid-P corrected). The median survival time of patients with normal CMI scores was 943 days compared with 488 days for those with depressed CMI (P = 0.03, log rank test; P = 0.04, Peto). The mortality risk of patients with normal CMI at entry to the study was, in the first 2 years of treatment, 40 per cent of that of patients with depressed CMI (95 per cent c.i. for relative risk 0.20-0.82, Cox regression). CONCLUSION: In patients with colorectal hepatic metastases, CMI is predictive of survival and a raised serum CEA level is associated with depressed CMI.
Twenty-two patients with colorectal cancer and synchronous unresectable hepatic metastases were treated by resection the primary tumour with concurrent insertion of an Infusaid infusaport system for regional chemoperfusion (hepatic arterial 20, portal venous 2). Four patients in addition had cryotherapy the liver metastases. Morbidity from the synchronous procedures was minimal. Median survival was 10 months. Four patients with poorly-differentiated tumours had a poor response, with a median survival of 3.75 months.
BACKGROUND: The present study reviews the nature of upper gastrointestinal complications of hepatic arterial chemoperfusion at a tertiary referral centre for the treatment of hepatic malignancy. METHODS: The patients involved in the present study all had major upper gastrointestinal (GI) haemorrhage and were undergoing hepatic arterial chemoperfusion. RESULTS: Eight patients had major upper GI haemorrhage. Three of these patients were not referred for surgical management, and all three patients died. The five patients who were admitted or transferred to our unit and who underwent surgery all survived. CONCLUSIONS: These complications are probably caused by extravasation of 5-fluorouracil (5-FU) following thrombosis of the gastroduodenal artery. The resulting cavity may perforate into the hepatic artery, portal vein, duodenum or biliary tree. Surgeons and oncologists should be aware of these complications. If upper abdominal pain occurs, chemoperfusion should cease immediately and an urgent investigation, which may include catheter angiography, gastroscopy and computed tomography (CT) scanning, should be carried out to exclude an hepatic artery pseudo-aneurysm.
The authors' clinical experience of treating almost exclusively inoperable liver malignancy in 149 patients by cryotherapy is reviewed. There was only one 30-day death; morbidity was modest. Postoperative carcinoembryonic antigen (CEA) changes were extremely predictive of outcome in patients with liver metastases from colorectal cancer. For the group in which CEA levels returned to the normal range, median survival exceeded 1000 days. In addition, the authors reported encouraging results with cryotherapy as an adjunct to resection.
Hepatic cryotherapy is a relatively new technique used to treat both primary and secondary tumors. This paper concerns the changes in serum aspartate transaminase (AST) in 45 patients following both single and double freeze with partial thaw cycles. There was considerable elevation in serum AST, greatest on the day of operation, and there was a significantly higher peak AST following the double-freeze cycles (1159; SE, 117.5) compared with single-freeze/thaw procedures (437; SE, 61.7). This finding indicates greater hepatocellular disruption which may be important both in planning clinical hepatic cryosurgery to achieve adequate destruction and also to avoid the morbidity of the cryoshock phenomenon.
Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant therapy for gastric cancer. We have demonstrated expression of histamine receptors on colon cancer cell lines and inhibition of their growth with cimetidine. Cimetidine also activates suppressor T cells and stimulates cell-mediated immunity. We therefore performed a randomized controlled clinical trial to determine the effect of cimetidine 400 mg given twice daily in conjunction with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized and 35 patients were eligible for further analysis. Both groups were well matched for pre-treatment characteristics. There was no difference in overall response. There was, however, a significantly increased rate of CEA response in the cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA response compared to none of eight in the control. Meaningful comparisons of overall survival cannot yet be made. This study demonstrates that cimetidine has encouraging activity in increasing CEA response in patients with metastatic colorectal cancer treated with chemotherapy. This observation needs to be extended in a larger randomized study, which is currently underway.
The use of cryotherapy for the treatment of some unresectable liver tumours has been clearly established as a therapeutic option. Intra-operative ultrasound has enhanced the process by enabling the surgeon to identify hepatic lesions and to allow visualisation of the freezing process to ensure that the cryolesion will include the tumour mass. The purpose of this paper is to provide a practical guide to surgeons who wish to perform cryotherapy of liver tumours. Patient selection and anaesthetic considerations are important. The surgeon should be able to deal with the complications of cryotherapy, particularly the intra-operative haemorrhage which may arise from cracking of the hepatic parenchyma as the iceball thaws. Follow-up is based on tumour marker assay and imaging of the liver and repeat cryotherapy can be considered for selected cases.
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Cryoablation is used to treat inoperable hepatic malignancy. We investigated the safety of cryoablation close to the inferior vena cava. Our sheep model showed that it was impossible to create an iceball around the inferior vena cava (IVC) unless this vessel was clamped. When subsequently the IVC was clamped and frozen for 30 min, the anesthetized spontaneously breathing sheep (n = 3) exhibited cardiac arrhythmias typical of hyperkalemia on release of the clamp. The plasma potassium in these sheep rose from a baseline mean (SD) of 5.0 (0.7) mmol/liter to 9.5 (0.9) mmol/liter after release of the clamp at the end of the freeze. These sheep also developed acute hypercapnoea and acidosis. These changes were avoided in subsequent sheep by assisting ventilation mechanically and hyperkalemia and arrhythmias were not seen in this group. Iceball cracking did not occur and the IVC remained intact in all cases. This work suggests that during hepatic cryotherapy of lesions close to the IVC, intraoperative monitoring of potassium is indicated, particularly if caval occlusion is required to achieve adequate iceball thermal distribution.
A consecutive series of 509 patients undergoing abdominal surgery were entered into a randomized, observer and patient blind, controlled, prospective, study to evaluate the efficiency of co-amoxiclav ('Augmentin', SmithKline Beecham, UK) compared with cefuroxime ('Zinacef', Glaxo, UK) plus metronidazole (Flagyl, M&B, UK) for the prevention of postoperative wound infections. One or three doses of antibiotics were given depending on the type of surgery and operative factors. Co-amoxiclav was given to 230 patients with a total wound infection rate of 5.6% and cefuroxime plus metronidazole were given to 225 patients with a total wound infection rate of 3%. The difference between infection rates was not significant. Both groups were comparable in terms of demographic details, type and duration of surgery, risk factors associated with surgical procedures and postoperative management. Although not statistically significant, a difference in the wound infection rate for those patients undergoing colorectal surgery was seen: 8/69 for the co-amoxiclav group and 2/79 for the cefuroxime/metronidazole group. The estimated cost to our hospital (October, 1993) of one dose of co-amoxiclav was less that half the cost of cefuroxime and metronidazole. This study demonstrates that co-amoxiclav is an effective prophylactic antibiotic for abdominal surgery.
Serum carcinoembryonic antigen (CEA) levels in 33 Australian patients with hepatic metastases from colorectal cancer were measured before and after treatment with hepatic cryotherapy and intra-arterial chemotherapy. Pre-operative and monthly postoperative CEA measurements were made and the lowest postoperative reading was recorded as a percentage fall from the pre-operative level. There was a highly significant association between the maximum percentage fall in CEA and survival. A 50% increase in the maximum percentage fall in CEA level was associated with one-tenth the risk of death (95% CI RR 0.03 to 0.32, Cox regression). It is estimated that an increase in the maximum percentage fall in CEA of 50% from 25 to 75% was associated with an increase in the median survival from 240 days to over 2 years.
Fifty consecutive patients undergoing resection of colorectal cancer were randomized to either receive cimetidine at a dose of 400 mg bd for a minimum of 5 pre-operative days, then intravenously for 2 postoperative days, or to act as controls. Baseline immune function was determined in all patients by in vitro testing of lymphocyte proliferation (LP) in response to mitogen, skin testing for cell mediated immunity (CMI) and measurement of lymphocyte subsets. Immune function was retested in both groups on the second postoperative day. In control patients the mean postoperative LP value was 41% of pre-operative levels (P < 0.0001) and the mean CMI reduced to 29% (P < 0.0001). Patients treated with cimetidine had no significant fall in these parameters. Numbers of T and natural killer (NK) cells fell after surgery in both groups, and B cell numbers were maintained in the cimetidine group. It is concluded that cimetidine reduces the immunosuppression that follows colonic resection.
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The widespread use of blood transfusion in major surgical procedures has led to concern about the immunosuppressive effect of transfusion on patients with underlying malignancy. Transfusion may also suppress the host response to infection. The cellular mechanisms of transfusion-associated immunosuppression may involve macrophage prostaglandin E2 (PGE2) in modulating the host response to cancer and infection. We previously observed that the transfusion of blood increased PGE2 production by unstimulated macrophages. To investigate this PGE2 associated immunosuppression, we studied the effect of transfusion of rats using a physiological stimulus of macrophage PGE2 production, bacterial endotoxin. In the same macrophages, we analysed intracellular oxidative activity. Both allogeneic and syngeneic blood transfusion were associated with increased PGE2 release by macrophages. This stimulation of PGE2 increased with duration of storage of blood. A similar effect of serum indicated that a humoral factor was involved. Endotoxin (50 ng/ml-500 micrograms/ml) stimulated PGE2 production in all transfused subjects. The lowest endotoxin concentration gave proportionately the greatest stimulation. Oxidative activity was down-regulated in macrophages of transfused rats, supporting an immunosuppressive role of PGE2 within the macrophage. An effect of surgery on the oxidative response was also detected.
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