Left retroperitoneal approach for inflammatory abdominal aortic aneurysms.
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Aorta, Abdominal↗
Biomedical subjects
B R Davidson
Publications and source records attributed to B R Davidson.
Intraoperative localization of colorectal cancers using radiolabelled monoclonal antibodies.
Radiation detectors may allow the intraoperative localization of small cancer deposits following administration of radiolabelled tumour-associated antibodies. This technique was evaluated in 16 patients with colorectal tumours (14 cancers, one adenoma, one lipoma) with the 111In-labelled monoclonal antibody (MAb) ICR2 which recognizes the tumour-associated epithelial membrane antigen (EMA). At operation counting was carried out (3 x 20 s per site) using a hand-held radiation probe over the primary lesions and any palpable lymph nodes in the mesocolon. The tumour to normal colon (T/NC) ratio of counts recorded at operation was more than 1.5:1 in eight of the 14 patients with cancer (mean(s.d.), 1.54(0.41):1) and 0.91:1 and 1.06:1 respectively in the two patients with benign tumours. Node to normal colon ratios were higher in lymph nodes containing metastases. The uptake of radiolabelled antibody (T/NC ratio) was higher in EMA-expressing cancers than in those not expressing the target antigen (mean(s.d.), 2.45(0.65):1 versus 1.40(0.20):1, P = 0.019). An abdominal tumour model was also developed. Radioactively filled containers of 0.5-10 ml representing tumour deposits were suspended in a tank of 111In solution representing the background activity found in normal tissues. The ratio of radioactivity in the 'tumour' to that of background varied from 2:1 to 8:1. The 'tumour' was considered to be detectable if the mean counts recorded over the 'tumour' exceeded the mean of counts recorded over background by three standard deviations. At a ratio of 2:1 only 'tumours' greater than 5 ml could be detected with a sodium iodide probe and those over 10 ml could be detected with a cadmium telluride (CdTe) probe. At a ratio of 8:1, 'tumours' of 0.5 ml could be detected with either probe. At all ratios and counting periods the NaI probe was more sensitive than the CdTe.
Aged↗
Evaluation of a technique for the intraoperative detection of a radiolabelled monoclonal antibody against colorectal cancer.
Occult tumour deposits may be localised at operation with a radiation detecting probe following the administration of a radiolabelled monoclonal antibody (MoAb) recognising a tumour-associated antigen. We have recently evaluated the clinical usefulness of this technique in detecting primary colorectal tumours targetted with an indium-111 MoAb. In the present study the physical characteristics of the two detector systems used were investigated; a sodium iodide [NaI(Tl)] scintillation detector and a cadmium telluride (CdTe) semiconductor probe. Limitations of the technique in use have been examined by testing the statistical significance of tumour detection using an abdominal phantom based on the currently available clinical biodistribution data for tumour uptake of radiolabelled MoAbs. The effect of tumour volume, antibody uptake, collimation and counting conditions was examined. Results indicate that tumours of 10 ml volume may be detected with the NaI(Tl) probe at the lowest levels of radiolabelled antibody uptake currently reported in the literature but that at higher published levels, lesions as small as 1 ml may be identified with both detector systems. Detector sensitivity and limited antibody specificity restrict the usefulness of the technique, although moderate improvements in tumour uptake may allow the detection of tumour deposits not clinically apparent. The statistical significance criterion used for this study could be an accurate and reliable indicator for tumour detection in vivo.
Colorectal Neoplasms↗
The effect of circulating antigen and radiolabel stability on the biodistribution of an indium labelled antibody.
This study has investigated two of the main problems with radiolabelled antibody imaging, the formation of circulating immune complexes (I.C.) and the non specific binding of radiolabel to the antibody molecule. Patients undergoing immunoscintigraphy with 111In labelled monoclonal antibody ICR2 were divided into three groups who received either the radiolabelled antibody alone (control, n = 12), the radiolabelled antibody which was incubated with the chelating agent diethylene triamine pentacetic acid (DTPA) prior to size exclusion chromatography (n = 6) or whose injectate was treated with DTPA and cold MAb administered intravenously prior to radiolabelled MAb administration (n = 6). Radiolabelled antibody uptake in abdominal organs was measured by region of interest analysis using a gamma camera with online computer and that in tumour and normal tissues by gamma well counting of biopsies. Circulating antigen and immune complex was measured by high pressure liquid chromatography (HPLC). The sensitivity of tumour imaging and the tumour uptake of radiolabelled antibody was not significantly different between the groups. Patients with high circulating antigen levels developed high levels of circulating immune complex but also had high tumour uptakes of radiolabelled antibody. Administration of cold MAb increased the splenic, but did not effect the tumour uptake of radiolabelled antibody and only minimally reduced levels of circulating immune complex. Chelate administration reduced the urinary excretion of radioactivity but increased the liver uptake of radioactivity. These results have shown that successful antibody imaging can be carried out despite high levels of circulating antigen, that large doses of unlabelled antibody are required to prevent immune complex formation and that removal of non specifically bound 111In does not reduce the liver uptake of radioactivity.
Aged↗
Caroli's disease misdiagnosed as hydatid liver cysts.
A 27 year old woman who presented with upper abdominal pain was found on ultrasonography to have multiple liver cysts consistent with hydatid disease. Three years previously she had undergone evacuation of multiple infected liver cysts thought to be due to hydatid disease. Computed tomographic scanning supported the diagnosis of hydatid disease affecting the right lobe of the liver. At laparotomy the right lobe contained multiple cysts which were removed by right lobectomy. Histology revealed congenital dilatation of the intrahepatic bile ducts with fibrosis (Caroli's disease) but no evidence of hydatid disease.
Adult↗
Immunoscintigraphy of colorectal cancer using a monoclonal antibody 77-1.
The monoclonal antibody (mAb) 77-1 recognizes epithelial membrane antigen (EMA) expressed by the majority of colorectal cancers. Following administration of indium-111 labelled 77-1, gamma camera imaging was carried out on 16 patients with known or suspected colorectal cancer prior to surgery or endoscopic laser therapy. Fourteen of the patients were found to have cancer, with one patient having two primary lesions. Two patients suspected of tumour recurrence were not found to have a lesion at laparotomy. Imaging before operation or laser therapy detected 10 out of 15 lesions (67%). Tumours which produced positive images were found to express the target antigen on immunocytochemical staining of the excised tumours. A mean tumour to normal colon ratio of 1.63 +/- S.D. 0.46 and a mean tumour to blood ratio of 3.60 +/- 1.48 were found at day 6 after antibody administration. A high uptake of radiolabel by the liver prevented the detection of hepatic metastases, present in three patients. Of the two patients with suspected recurrence a false positive scan was found in one owing to the presence of inflammatory tissue. Indium-111 labelled 77-1 may have a role in the imaging or targeting of colorectal cancer.
Aged↗
Detection of occult nodal metastases in patients with colorectal carcinoma.
Immunohistochemical study may be used for detecting micrometastases by their expression of tumor-associated antigens. In 48 specimens of colorectal cancer from 47 patients, 49 of 249 lymph nodes (median, five per patient; range, 2-11) examined by light microscopic study contained tumor deposits. Sections of all lymph nodes were also examined by immunohistochemical study for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression using the indirect immunoperoxidase staining method. All 49 lymph node metastases (100%) from 20 patients stained positively for CEA and 45 (92%) expressed EMA. Of the 200 lymph nodes without metastases on light microscopic examination, anti-CEA revealed a single micrometastasis in a patient staged as Dukes' B. No additional metastases were detected with anti-EMA. In this series of patients immunohistochemical study has, therefore, influenced the histologic staging in only one patient (2%) and thus does not offer a significant benefit over conventional histologic staging.
Antibodies, Monoclonal↗
Endoscopic sphincterotomy in hepatic hydatid disease open to the biliary tree.
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Biliary Fistula↗
Restorative proctocolectomy: a procedure for the district general hospital?
Restorative proctocolectomy is widely regarded as the surgical procedure of choice for patients with ulcerative colitis or familial adenomatous polyposis, the majority being carried out within specialised regional centres. The use of this procedure outside such centres has been investigated by reviewing the results from a District General Hospital (DGH) over the 8 year period 1981-1989. Seventeen patients (11 male and 6 female with a median age of 36 years) underwent total colectomy and ileoanal anastomosis with formation of a pelvic reservoir (TC-IA). Fourteen had ulcerative colitis (UC), 2 familial adenomatous polyposis (FAP) and one a colonic and rectal cancer. Three pouch designs were used ("S" in 7, "J" in 8 and "W" in 2) with no operative or perioperative deaths. Further laparotomy was required in two patients for adhesions and pelvic sepsis. Functional results were assessed in 16 patients at a mean of 5 years after surgery. The median daily stool frequency was 5 (range 2-6). Twelve of the 16 patients defaecate spontaneously, 2 regularly self-catheterized and 2 do so occasionally. None of the patients is incontinent of formed or liquid stool but one has occasional soiling. These results suggest that TC-IA may be satisfactorily performed outside a specialised unit.
Adenomatous Polyposis Coli↗
Inhibition of the hepatocyte uptake of radiolabelled monoclonal antibodies by chelating agents.
The imaging of small abdominal tumours with indium 111 labelled monoclonal antibodies (MAbs) is often obscured by the uptake of activity into the heptocytes of normal liver tissue. A model has therefore been developed to analyse reagents which may inhibit the hepatocyte uptake of 111In-MAb whilst preserving tumour uptake. Primary rat hepatocyte cultures and an epithelial membrane antigen (EMA) expressing tumour cell line (MCF7), recognised by the EMA-specific MAb ICR2, were obtained in tissue culture. Monolayers of both cells were incubated with the 111In-MAb with or without the additional reagents and the cell uptake then measured and expressed per milligram of cell protein using a Lowry protein assay. No preferential reduction in hepatocyte uptake was noted by incubating cells with either saturated or unsaturated transferrin. The chelating agent, diethylene triamine penta-acetic acid (DTPA), however, significantly reduced the uptake of activity in hepatocytes but not the tumour cell line (P less than 0.05). An optimum concentration and time period for incubating DTPA with labelled MAb was established. The mean hepatocyte uptake was reduced by 80% with a 1 h incubation with 1 mM DTPA. These results suggest that DTPA may have a role in reducing the liver uptake of radioactivity in patient studies using 111In-MAb.
Animals↗
Immunoscintigraphy of colorectal cancer with an antibody to epithelial membrane antigen (EMA).
Immunoperoxidase staining of LICR-LON M8, a mouse monoclonal antibody reactive with epithelial membrane antigen, showed a strong reaction with colorectal cancer. This finding prompted an immunoscintigraphic study of colorectal cancer patients using this antibody. Sixteen patients had external gamma scintigraphy after intravenous injection of indium 111-labeled M8. Positive scans were obtained in 11 of the 13 patients with primary colorectal cancers, and 2 of the 3 patients with recurrent tumors. The high indium 111 background in the liver prevented the detection of hepatic metastases in 5 patients. Twelve patients had samples taken of tumor, normal colon, and venous blood at the time of surgery. The ratio of labeled antibody uptake in tumor to that of blood was 5.1 (+/- 3.6 S.D.), which was significantly different (P = 0.001) to that of the similar ratio for normal colon (2.0 +/- 1.6 S.D.). The tumor to normal colon uptake ratio was 2.6 (+/- 1.3 S.D.). These results suggest a specific uptake of indium 111-labeled M8 by colorectal cancer.
Aged↗
Fibrolamellar carcinoma arising in an abnormal liver.
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Adolescent↗
Comparative study of carcinoembryonic antigen and epithelial membrane antigen expression in normal colon, adenomas and adenocarcinomas of the colon and rectum.
The heterogeneous nature of tumour antigen expression may require selection of monoclonal antibodies on an individual patient or tumour basis to allow adequate tumour localisation. Carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) expression has not previously been compared in colorectal cancer patients. Sections of cancer (n = 52), adjacent normal colon (n = 45), synchronous adenomas (n = 11) and nodal metastases (n = 49) were examined by indirect immunoperoxidase staining in 51 consecutive patients with colorectal cancer using monoclonal antibodies to CEA and EMA. The percentage of cells with positive staining in the primary tumours was graded 1: less than 25%, 2: 25-49%, 3: 50-75%, 4 greater than 75%. All primary colorectal cancers expressed CEA and 43 of 52 expressed EMA (83%). Grading showed CEA greater than EMA in 39, equal in 11 and less in two. Well differentiated cancers were more frequently graded three or four for CEA staining (23 of 27) than moderately differentiated cancers (11 of 22) (p less than 0.01). Equivalent figures for EMA were four of 27 and three of 22 (not significant) (NS) although the majority (86%) were graded 1 and 2. Grade 1 CEA expression was found in six of 15 proximal and only two of 37 distal lesions (p less than 0.01, chi 2 test) while for EMA equivalent figures were three of 15 and six of 37 (NS). Nodal deposits all expressed CEA and 45 of 49 expressed EMA (92%); 29 of 45 normal colon sections showed CEA expression (64%) as did all adenomas. EMA was not expressed by normal colon or adenomas. These results suggest that EMA expression is more specific but less sensitive than CEA for colonic cancer and is independent of tumour differentiation and site. Thus selecting monoclonal antibodies to CEA or EMA based on tumour biopsies may allow improved tumour localisation for imaging or therapy in patents with colorectal cancer.
Adenocarcinoma↗
Biochemical prediction of gallstones in acute pancreatitis: a prospective study of three systems.
Three clinicobiochemical systems have been proposed for predicting gallstones in acute pancreatitis based on one, three and five factors respectively, but have not been compared in a single prospective study. System 1 is based on the serum transaminase alone; system 2 uses alkaline phosphatase and bilirubin in addition to transaminase; and system 3 involves female gender, age, amylase and alkaline phosphatase in addition to transaminase. Over the 4-year period 1983-86, 368 patients with 391 episodes of acute pancreatitis had clinicobiochemical analysis within 48 h. Of these episodes, 220 were related to gallstones (56 per cent), 62 to alcohol (16 per cent) and 109 to other aetiologies or were idiopathic (28 per cent). Significant differences were found between the biliary and non-biliary groups with respect to sex (139 versus 59 women, P less than 0.002), age (65 +/- 17 versus 52 +/- 19 years, P less than 0.0001) and serum amylase (6041 +/- 6335 versus 4546 +/- 3990 units/l, P less than 0.0001), alkaline phosphatase (257 +/- 225 versus 141 +/- 137 units/l, P less than 0.0001), alanine transaminase (221 +/- 227 versus 72 +/- 119 units/l, P less than 0.0001) and bilirubin (40 +/- 39 versus 24 +/- 30 mumol/l, P = 0.0001). The sensitivity and specificity was 75 per cent and 74 per cent for the one-factor system, 74 per cent and 78 per cent for the three-factor system and 62 per cent and 80 per cent for the five-factor system. The predictive value of a positive result was 78.8 per cent, 81.5 per cent and 80.1 per cent and of a negative result 69.4 per cent, 70.1 per cent and 62.3 per cent for the three systems respectively. The performances of the one- and three-factor systems were marginally better than that of the five-factor system; the one-factor system, however, had the advantage of simplicity.
Acute Disease↗
Role of duodenal bile crystal analysis in the investigation of 'idiopathic' pancreatitis.
Duodenal bile crystal analysis for the detection of gallstones was assessed in 26 patients with acute pancreatitis of known aetiology (11 attributable to gallstones and 15 to alcohol) and in 37 patients without a history of acute pancreatitis (21 with gallstones and 16 without). The sensitivity was 64-67 per cent and the specificity was 94-100 per cent in these groups. Analysis of duodenal bile from 14 patients with 'idiopathic' pancreatitis revealed calcium bilirubinate crystals (but not cholesterol crystals) in 5 patients (36 per cent). Gallstones were confirmed at cholecystectomy in three of these patients and also in one other patient who had a gallstone on a 'late' ultrasound examination but was negative for crystals. Thus 29 per cent of the original 'idiopathic' group had gallstones confirmed. Gallstone analysis showed that pigment stones were present in 7 of 31 (23 per cent) non-pancreatitis controls compared with 9 of 13 (69 per cent) pancreatitis patients (P = 0.0048). These results suggest that duodenal bile crystal analysis (involving both calcium bilirubinate and cholesterol crystals) may be a useful technique for the investigation of patients with 'idiopathic' pancreatitis.
Acute Disease↗
A comparison of carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA) in human colorectal cancer.
The development of monoclonal antibodies (MAbs) to tumour-associated antigens has allowed the successful radioimmunolocalization of a variety of tumours and has provided a basis for targeted therapy. In patients with colorectal cancer, antibodies to CEA have been the most widely used for imaging, but their role in targeted therapy may be inhibited by their reaction with normal tissues and with circulating CEA. Epithelial-membrane antigen (EMA) is expressed by most epithelial tumours, including colorectal cancers, and antibodies to EMA may provide a satisfactory alternative. We therefore compared two high-affinity MAbs, one to CEA (C46) and one to EMA (ICR2), in tissues obtained from 31 patients with cancer (18 primary colonic, 6 nodal metastases and 7 liver metastases), 14 patients with adenomatous polyps and 17 with normal colon. The indirect immunoperoxidase staining reaction was used and the results classified as either positive or negative. A heterogeneous pattern of staining was found for both antibodies. ICR2, the anti-EMA, reacted with slightly fewer colonic cancers than C46, the anti-CEA antibody (83% vs. 100%) and a similar number of metastases. Most noticeable was the minimal reaction of anti-EMA with normal colon (12% vs. 71%) and benign polyps (7% vs. 79%) in comparison to anti-CEA. This would suggest a possible role for ICR2 in the radioimmunolocalization and targeting of colorectal cancer.
Antigens, Neoplasm↗
Endoscopic sphincterotomy for common bile duct calculi in patients with gall bladder in situ considered unfit for surgery.
Endoscopic sphincterotomy (ES) was attempted in 106 patients with common bile duct (CBD) calculi and gall bladders present, who were considered unfit for surgery on the grounds of age and frailty alone (35%) and/or the presence of major medical problems (65%). Endoscopic sphincterotomy was successful in 105 patients (99%). Early ES related complications occurred in 21 patients (19.8%). Twelve hospital deaths occurred (11.3%), although this was due to biliary causes in only five (4.7%) and one of these was moribund on admission. Complications were more frequent in those in whom initial ES did not clear the common bile duct (30.4%) compared with those in whom this was (11.7%; p = 0.0164). The mortality was also greater in patients in whom there was no ERCP proof of CBD clearance (p = 0.01) unless operated upon. Twelve patients developed gall bladder complications (11.3%) including five with empyema (4.7%). Analysis of clinical, haematological, and biochemical factors together with ERCP findings showed that the only factor which had any value in predicting gall bladder complications was pre-existing cholangitis. The present series was compared with another using ES as a definitive procedure, and with a surgical series. Although there were significant differences in outcome, differences with respect to medical risk factors and the incidence of complications of CBD stones (jaundice, cholangitis, and acute pancreatitis) were striking. Further analysis of these factors may allow a clearer definition of patients most likely to benefit from either ES or surgery.
Age Factors↗
Invasive amoebiasis: an unusual presentation.
A 63 year old Asian woman who presented with three week's abdominal pain was found to have a hard right iliac fossa mass and rectal ulceration. Profuse rectal bleeding necessitated a laparotomy. An inflammatory paracaecal mass with fistulae involving appendix, small bowel, and bladder was excised with exteriorisation of the bowel ends. Microscopy showed invasive amoebae. Re-anastomosis was successfully done after treatment with metronidazole and diloxanide. There are no previous reports of a paracaecal amoeboma with fistulae to either the appendix, or urinary bladder.
Amebiasis↗