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Scintimammography with Tc-99m-MIBI has been shown to be an effective adjunct to imaging of the breast with mammography. Uptake of Tc-99m-MIBI is particularly high in sites of non- calcified cancer and ductal carcinoma in situ (DCIS), and as a consequence it may be possible to use this method of imaging in identifying multifocal or multicentric disease. The aim of this study was to evaluate the efficacy of preoperative scintimammography in the detection of multifocal and multicentric breast cancer and compare these results with mammography. A retrospective review was performed of 353 women imaged with Tc-99m-MIBI as part of the clinical assessment of their suspected primary breast cancer. The results of the scintimammography and mammography were then compared with the final pathological diagnosis obtained after mastectomy in all patients. Histopathological assessments of breast tissue from mastectomy confirmed 40 women (12%) had multifocal (34) or multicentric (six) breast cancer. Scintimammography correctly identified 39 of these cancers and the multifocal or multicentric character of the cancer was identified in 22 (52%.) of these patients. Anatomical imaging performed in all 40 patients including 25 with mammography alone, mammography and ultrasound in 11 cases and ultrasound alone in four patients. Anatomical imaging identified cancer to be present in 28 patients (70%) and the combination of mammography and ultrasound identified correctly that the cancer was multifocal or multicentric in eight patients (22%). In this study scintimammography was able to identify more cases of multifocal and multicentric cancer than mammography and/or ultrasound. In patients where pre-operative identification of multicentric or multifocal disease can alter treatment scintimammography may be a useful investigative tool. ((C) 2001 Lippincott Williams & Wilkins)

Mammography, whilst remaining the first line imaging investigation of suspected primary breast cancer, can be difficult to interpret in patients with fibrous or dense breasts. Radionuclide imaging of the breast (scintimammography) has been suggested as an additional test. The aim of this study was to perform prospectively a comparison of the two techniques in a population with suspected breast cancer. Seventy such patients, mean age 54 years (range 57 years, 28-85) with 74 suspicious breast lesions were studied. They were imaged 5-10 min after intravenous injection of 740 MBq of Tc-99m sestamibi. Prone lateral and anterior supine views with and without markers were performed. All patients had histological confirmation of the nature of the breast lesions by limited incisional biopsy or definitive wide local excision, or cytological confirmation on fine needle aspiration. All patients had X-ray mammography. There were 53 malignant breast tumours and 21 benign lesions. Scintimammography correctly diagnosed 47 breast cancers, and yielded true-negative results in 12 benign breast lesions. There were six cases of false-negative results and nine false-positive results. Four scans were reported as equivocal. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 89%, 52%, 84% and 67%, respectively. X-ray mammography diagnosed correctly 37 malignant tumours, and in 12 benign lesions the results were true negatives. Ten studies were reported as equivocal. The sensitivity, specificity, PPV and NPV were 70%, 57%, 80% and 43%, respectively. The accuracy of Tc-99m sestamibi scintimammography was better than X-ray mammography though this was not significant (McNemar's test). Fewer equivocal results were obtained with scintimammography. Scintimammography may therefore have a role in the diagnosis of primary breast cancer when X-ray mammography is equivocal or unhelpful.

Prone single photon emission tomography (SPET) was performed in 24 patients with suspected primary or recurrent breast cancer to determine if this technique offers more accurate imaging than that obtained from planar scintimammography. All patients were imaged on a specially designed couch with two cushion inserts. The first insert was lined with lead and was used to perform prone lateral planar scintimammography 5 min after the injection of 740 MBq 99Tcm-MIBI. The second insert did not contain lead and was used to perform a prone SPET acquisition for 30 min immediately after planar imaging. The results of both studies were read independently and there was agreement between the two techniques in 23 cases (96%). All cases of cancer proven on histology were found on planar imaging, but a 4-mm ductal cancer was missed on prone SPET. This was thought to be due to activity from this medial cancer being obscured by the star artefact produced by back-projection reconstruction from activity in the heart. There were two false-positive studies with both techniques. However, prone SPET enabled better localization and characterization of breast cancers than planar imaging. Prone SPET imaging of the breast produces results similar to prone lateral imaging and may be used instead of planar imaging if a reduced total acquisition time is desirable. Care must be taken when reading scans in the presence of small tumours near the heart when back-projection reconstruction techniques are used.

A prospective trial was performed to assess the accuracy of 99 Tc m -methoxyisobutyl isonitrile ( 99 Tc m -MIBI) scintimammography and X-ray mammography in 18 patients (mean age 58 years, range 46-79 years) with suspected recurrent breast cancer in the breast and/or loco-regional tissues. All patients had been diagnosed to have breast cancer 1-23 years before scintimammography. Two patients had undergone mastectomy, so that a total of 34 breasts were studied with X-ray mammography and with prone-lateral and anterior scintimammography. Any abnormalities on X-ray mammograms and scintimammograms were noted, as was any additional local or nodal uptake of 99 Tc m -MIBI. The nature of any lesion seen with either modality, or in which there was a clinical suspicion of recurrence, was confirmed by cytological or histological examination of tissue samples. There were nine breasts with recurrent cancer in eight patients. X-ray mammography identified six of these cancers. 99 Tc m -MIBI scintimammography identified eight of nine recurrent breast cancers (the one cancer not seen was positive on X-ray mammography). In the 26 breasts without cancer, two were reported as having changes consistent with cancer and one was reported equivocal. There were three false-positive and one equivocal scintimammograms. The accuracy of 99 Tc m -MIBI scintimammography within the breast (85%) was similar to X-ray mammography (82%). Axillary lymph node recurrence occurred in five patients, four of whom were positive with 99 Tc m -MIBI. An additional patient had focal uptake of 99 Tc m -MIBI at the site of recurrent cancer on the anterior chest wall. In conclusion, 99 Tc m -MIBI scintimammography may provide useful complementary information in patients with suspected recurrence of cancer in the breast or loco-regional tissues.

Malignant melanoma and primary breast cancer are tumours which have an association based on genetic and hormonal factors. It is not generally appreciated that there is an increased incidence of melanoma in patients with breast cancer and vice versa. We present two cases of patients who developed breast carcinoma following previous treatment for melanoma. We review previous reports of this association and examine the theoretical reasons why this should be so. Medical practitioners should be aware of this association in order to alter their index of suspicion appropriately.

Five patients in deep hepatic coma due to fulminant hepatitis were treated with 6 extracorporeal pig-liver perfusions. In three patients the acute hepatic necrosis was due to viral hepatitis, in one to an overdose of paracetamol, and in one patient liver failure was due to acute fatty liver of pregnancy. Corticosteroids and exchange transfusion were not used. All patients showed severe electroencephalographic changes and one patient who recovered showed virtually no cerebral activity. Perfusion lasted for 3.5-5.5 hours, during which a 48-94 litre exchange from pig liver to patient was effected. Improvement in the level of consciousness and in the electroencephalogram was noted in all patients. Serum-bilirubin levels fell significantly. Detailed studies of cerebral metabolism in one patient showed a striking improvement in the cerebral oxygen consumption and in the oxygen/glucose index. Complications during and after perfusion included bleeding, renal and respiratory failure, hypoglycaemia, hypokalaemia, hypocalcaemia, psychosis, and pancreatitis. Two patients regained full consciousness and are leading a normal life 13 and 8 months after pig-liver perfusion. Liver biopsy shows recovery of normal hepatic structure. Three patients died 2 hours to 10 days after liver perfusion. One patient died from massive gastrointestinal haemorrhage associated with fatty liver of pregnancy; in the second patient necropsy showed a shrunken liver with no evidence of regeneration; the third patient had a severe acute haemorrhagic pancreatitis from which he died although the level of consciousness was improving. These results are encouraging, but this treatment must be reserved for patients in acute liver failure who have the potential for complete recovery.

A technique of orthotopic liver transplantation in the pig is presented. Details of modifications in anaesthesia, collection of blood, and preparation of the donor liver are given. The use of a single venous by-pass, end-to-end hepatic artery anastomosis, and vagal crush with pyloromyotomy to prevent gastric ulceration have simplified the procedure and so reduced the operation time.

Summary Acute fulminant hepatitis leads to complex biochemical and circulatory disturbances including coma. These can be predicted to some extent by knowledge of the functions of the normal liver cells. Ineffective haemostasis, coma, hypoglycaemia, electrolyte abnormalities, hypotension and renal circulatory failure are particularly important. Management should be governed by the abnormalities found in the individual patient. Fluid overload and sedation must be avoided. More complex methods of temporary hepatic support such as exchange transfusion or perfusion of the isolated pig’s liver should only be considered after simpler methods of correction have been attempted for a reasonable period of time and found wanting. The prognosis of acute hepatocellular failure reaching the stage of deep coma is very poor, the mortality being about 80-90%.

A technique is described for the treatment of patients in acute liver failure by perfusing their blood through an isolated pig liver. The circuit is arranged so as to allow good function of the perfused liver, irrespective of the condition of the patient or the blood-flow from his arterial cannula. of 3 patients so treated, 2 are alive and well.

Five patients in deep hepatic coma due to acute liver failure were treated by perfusion of pig liver. All patients showed severe electro-encephalographic changes and 1 patient who recovered showed virtually no cerebral activity. An exchange of 48–94 litres from pig liver to patient was achieved during the procedure. All patients showed neurological improvement after perfusion. Three patients died 2 hours to 10 days after liver perfusion. The remaining 2 patients made a full recovery and are leading a normal life 9 and 14 months after perfusion.

The fibrinolytic system was studied in primary biliary cirrhosis (16 patients) and large bile duct obstruction (10 patients, nine of whom had carcinoma). Plasma fibrinolysis (plasminogen activator activity) was decreased and fibrinogen increased in both groups of patients, particularly in those with large duct obstruction. These changes were related to the degree of cholestasis. Plasminogen activator activity was inversely related to serum triglyceride levels in patients with primary biliary cirrhosis. Urokinase inhibitors were decreased in both groups and antiplasmins increased in patients with large duct obstruction; fibrin/fibrinogen degradation products were normal in primary biliary cirrhosis and moderately increased in large duct obstruction. None of these fibrinolytic indices was related to the degree of cholestasis. Fibrinolytic activity and fibrinogen returned almost to normal levels after palliative surgery in the three patients with large duct obstruction who were studied. The decreased plasma fibrinolysis and increased fibrinogen may be due to altered lipid metabolism in cholestatic jaundice. In patients undergoing surgery for large duct obstruction there may be an increased risk of thrombosis.

The radiographs of 100 patients with acute pancreatitis were reviewed and compared with 100 controls by two radiologists and a surgeon. Our aim was to assess the frequency and usefulness of the signs described in the literature. Calcification of the pancreas was seen in one case only. Abnormalities of the biliary tree (visible gallbaldder, biliary gas and gallstones) were seen in 10%. The left psoas shadow was more frequently absent in the pancreatitis series. Paucity of gastrointestinal gas although observed in 12 cases was ascribed to vomiting. A more important sign was the gaseous outline of an adynamic duodenal loop which was seen in half of the patients examined in the left lateral decubitus position. Dilated jejunum was seen in 31 cases, associated with sentinel loops in 10 and multiple fluid levels in 25 patients. Dilatation of thet ransverse colon was the most constant colonic sign (18%), but the colon 'cut-off' sign was not seen. It was concluded that the most prominent signs in order of importance are a gaseous distension of the duodenal loop, gas in the duodenal cap, a dilated transverse colon and the sentinel loop. The gasless abdomen is a striking but rare sign and in our series was always associated with severe pancreatitis.

Serial photography with strict technical control is used as a means of monitoring the response to treatment in patients with advanced breast cancer. Patient positioning, illumination, image scale, exposure and photographic processing conditions are considered. A simple means of enhancing the appearance of microvascular changes in the skin was devised to provide early detection of skin flush and nodules. Infrared absorption photography is being evaluated as another means of assessing the progress of the condition and its response to treatment. These techniques are part of a multilateral programme used to chart the progress of the disease. Serial photography was used in 39 patients. Photographic evidence was clinically useful in 28 patients and affected further clinical management in 8 cases.

Skeletal scintigraphy is claimed to be a sensitive method of detecting bone metastases, particularly since the introduction of the Technetium-99M radionuclides linked to bone-seeking diphosphonate compounds, such as methylene diphosphonic acid (MDP) (Bull et al, 1977a). Quantitative estimation of the uptake of these compounds has been advocated as a means of assessing the progress of bone metastases and of their response to treatment (Bull et al, 1977b). It requires the use of a gamma camera attached to a computer system.

Die Ergebnisse klinischer und einiger experimenteller Arbeiten beweisen, das die Leber normalerweise eine hemmende Wirkung auf das fibrinolytische System ausubt. Es wird angenommen, das diese Wirkung mit der Clearance des Plasminogenaktivators [3,4, 8] und der Inhibitorensynthese [9, 10] zusammenhangt. In der vorliegenden Studie sollten die Mechanismen der antifibrinolytischen Aktivitat der Leber mit Hilfe der extrakorporalen Schweineleberperfusion untersucht werden.

Summary Ascitic ultrafiltration and reinfusion of protein concentrate is of value in selected patients and is, in general, well tolerated. Patients with massive ascites and an unsatisfactory response to diuretic therapy are most suitable, but those with ascitic infection, pulmonary oedema, and terminal liver disease are excluded. Although two of our patients had malignant ascites, reinfusion is not recommended for such patients. Persistent pulmonary oedema was a contributory cause of death in two patients, and was attributed to reinfusion. Intraperitoneal haemorrhage may occur from a perforated collateral vein and close observation of patients must be continued after the peritoneal catheter has been removed. A clogged ultrafilter was cleared with urokinase, and further studies of this are indicated. After ultrafiltration about half the patients were satisfactorily controlled with diuretic drugs, although there is no evidence that reinfusion produces a sustained improvement in diuretic responsiveness.

The skeleton is the commonest site of distant metastatic disease in breast cancer. Conventional methods such as radiography are relatively insensitive in picking up these lesions. In recent years the introduction of new isotopes such as Technetium — 99m Methylene Disphosphosphonate (99Tc MDP) has made high quality bone scans available, but their role in the detection and further management of bone deposits requires to be established.

The growth tempo of tumours has, until recently, received little attention in relation to the clinical management of cancer, yet, when it can be recognised (as in the case of inflammatory cancer), the dynamic biological characterisation of a tumour may provide a much better clue to its clinical behaviour than does its histopathological picture. Even now, information on the growth rate and kinetics of tumours is scanty and based on studies of a small number of tumours. This chapter will examine clinical behaviour of rapidly growing malignant tumours in relation to underlying biological phenomena, under the following headings: Inflammatory cancer and other rapidly growing tumours Clinical demonstration of rapid growth Relationship of rapid growth to biological indices Changes in tumour growth rate Relationship of rapid growth to immune deficiency states Prospects for clinical detection of rapidly growing tumours

1. Changes in the perfusate activities of aspartate transaminase, lactate dehydrogenase, its ‘LD-5’ component, sorbitol dehydrogenase, ornithine carbamoyltransferase, and the isoenzyme patterns of lactate dehydrogenase and aspartate transaminase, were investigated in eleven perfusions of pig liver with human blood in order to assess liver cell damage during perfusion. 2. The aspartate transaminase values were a sensitive indicator of liver damage provided that, as was usually the case, the degree of haemolysis was small. Appearance on electrophoresis of the mitochondrial isoenzyme of aspartate transaminase indicated severe liver damage. 3. Measurement of sorbitol dehydrogenase activity was also shown to be a sensitive index of liver cell damage, and had the advantage that haemolysis did not interfere. 4. Measurement of total lactate dehydrogenase activity was unreliable as this largely reflected the degree of haemolysis rather than liver cell damage. However, the isoenzyme pattern of lactate dehydrogenase on electrophoresis distinguished liver cell damage from haemolysis. The chemical determination of ‘LD-5’ was not a sensitive index of pig liver damage as this fraction is found only in low concentration in pig liver. 5. Ornithine carbamoyltransferase was also found not to be a sensitive marker of liver cell damage.

Plasminogen activator activity was studied in bile and perfusate during extracorporeal pig liver perfusion. Plasminogen activator activity in bile was up to 58 times greater than in perfusate. A high level of plasminogen activator activity in bile was also found after the addition of urokinase to the perfusate. These results suggest that bile is the main route of active excretion of plasminogen activator and urokinase from the liver in experimental liver perfusion.

Antifibrinolytic activity was studied in the perfusate during extracorporeal pig liver perfusion. Heparinized human blood was used in 5 perfusions and a buffered electrolyte dextran solution in one perfusion. There was a marked release of the antifibrinolytic substance from the liver. This release was impaired by hypothermia and hypoxia, suggesting hepatic synthesis of the antifibrinolytic substance. The high levels of antifibrinolytic activity attained during perfusion may be clinically significant, reducing the risk of haemorrhage by preventing gross increases in fibrinolysis.

The electroencephalogram (EEG) has been used in the assessment and selection of patients in coma due to acute liver failure for extracorporeal pig-liver perfusion. The response during and following perfusion was also monitored using the EEG. In 55 consecutive patients a stage of the EEG was recognized beyond which spontaneous recovery has not been seen. This stage is characterized by a decreasing amplitude associated with a low frequency, blunting of triphasic waves, if previously present, and periods of flattening. Five patients who had reached this stage were treated by liver perfusion. Following perfusion, two patients, including one who initially had no cerebral activity, fully regained consciousness and have survived 24 and 30 months. The EEG in these patients showed a dramatic improvement following perfusion but full return to normal was not seen for four weeks although they were conscious within 48 hours. A further two patients improved clinically although the EEG remained featureless and of low amplitude; both died. The persistence of an EEG of low amplitude and with little or no rhythmic activity is ominous despite the initial clinical improvement. The fifth patient died shortly after perfusion before a further EEG was recorded. Studies of cerebral metabolism showed a good correlation with the EEG and clinical state in three of four patients before and after perfusion. EEG monitoring should be part of the routine management of patients with acute hepatic failure. The EEG has been useful in the assessment of these patients and has been shown to improve following liver perfusion.