SYMPOSIUM ON LIVER DISEASES

859

Conferences and

and normal in of doubt.

Congresses

A SYMPOSIUM on Modern Aspects of Liver and Biliary was held on March 28-April 1 at the Postgraduate Medical School of London. The meeting was planned by Dr. SHEILA SHERLOCK, who arranged a comprehensive course of lectures, demonstrations, and discussions of subjects with practical applications in general medicine and surgery. Dr. CHARLES NEWMAN, dean of the postgraduate school, welcomed more than 60 participants, including Dr. J. CAROLi and Dr. V. SCHWARTZMANN from Paris, Dr. S. MADSEN from Copenhagen, Dr. G. A. MARTINI from Hamburg, and Dr. R. MANGOLD from Lausanne.

Disease

Jaundice

day’s

programme

concerned

problems

associated with jaundice, and Prof. E. J. KING acted as chairman. Prof. N. F. MACLAGAN reviewed the range of liverfunction tests and pointed out that certain tests might be positive in diseases which were not primarily hepatic,

including heart-failure, chronic rheumatism, malaria, and glandular fever. A poor prognosis was associated with serum-albumin levels of less than 2 g. per 100 ml. in medical cases; and the failure of an increased to respond to vitamin-K injections unfavourable sign in obstructive jaundice. For routine use, he recommended examination of the urine for bilirubin, bile salts, and urobilinogen, estimations of serum-bilirubin and alkaline-phosphatase levels, and thymol-flocculation and colloidal-gold tests. Measurement of serum-proteins and bromsulphalein retention should be added if indicated. Dr. Sherlock classified jaundice and discussed its clinical management. She stressed the significance of pain and pruritus in the history, and the finer points which might emerge from a thorough physical examination. In the treatment of acute hepatitis, she considered that diet should be dictated by the patient’s appetite and that the inclinations of the patient should be taken In into account in the early stages of mobilisation. chronic obstructive jaundice, methyl testosterone for pruritus, fat-soluble vitamins by injection, and calcium tablets were of value. Dr. F. 0. MACCALLUM said that the lack of a susceptible animal host hindered studies of virus hepatitis. Virus A, causing infective hepatitis, was present in blood and fseces, but a carrier state had not been proven. Serum hepatitis was caused by virus B, which had only been isolated from blood, and a carrier state of uncertain duration had been demonstrated. Gamma-globulin might be given to contacts of infective hepatitis, but was of dubious value in serum hepatitis. The two viruses were immunologically different. The significance of positive flocculation tests as an isolated finding after hepatitis was discussed and it was agreed that a careful follow-up was indicated, but no active measures need be taken. Blood-donors should be rejected if they had had an attack of hepatitis. Carriers may not have had overt hepatitis and the duration of the carrier state was unknown. On the question of " cholangiolitic " hepatitis, Dr. Sherlock remained unconvinced. Dr. Caroli pleaded for the wider use of peritoneoscopy in the differential diagnosis of jaundice. Prof. IAN AIRD considered that this technique demanded great experience and’ admitted that the type of jaundice was often obscure at laparotomy. By serial sampling of blood and duodenal contents following an intravenous dose of bromsulphalein, Dr. Caroli had found that the excretion time was delayed in obstructive jaundice

prothrombin-time

was an

and he advocated this test in

Cirrhosis and Portal

SYMPOSIUM ON LIVER DISEASES

The first

hepatitis,

cases

Hypertension

chairman when Dr. Sherlock introduced this subject and explained that the term "cirrhosis" should be restricted to conditions in which the lobular architecture was disturbed. A similar histological picture resulted from many causes, because of the limited response of the liver to injury, while the clinical features were dominated by those of portal hypertension and inadequate liver-cell function. Current views on the pathogenesis of portal hypertension and its clinical consequences (portal collateral circulation, splenomegaly, and hsematological changes) were ably -summarised by Dr. P. C. REYNELL. In 20% of patients with portal hypertension, there was no liver disease and the cause was usually an obstructive lesion of the portal vein. The technique of percutaneous transplenic portal venography was demonstrated by Dr. Sherlock, Dr. R. E. STEINER, and Dr. M. D. TURNER. The application of this investigation to the diagnosis of portal hypertension and its special use in preoperative assessment were discussed. Dr. W. H. J. SUMMERSKILL and Dr. G. A. MARTIN showed that the pressure in an occluded hepatic vein, measured through a cardiac catheter, provided an alternative index of portal pressure and that other information could also be derived from catheterisation of the hepatic veins. A normal occluded-hepatic-vein pressure, with evidence of portal hypertension, was found in patients with thrombosis of the portal vein. Prof. R. MiLNES WALKER discussed the management of portal hypertension. The danger of severe haemorrhage was the only indication for major surgery, but poor liver function or an unsatisfactory general condition might preclude operation. Surgical treatment should not be considered for the relief of ascites, but this complication did not necessarily contra-indicate operation. A preliminary portal venogram was a great help and, when practicable, an end-to-side portacaval anastomosis was the operation of choice. Other portal-systemic shunts often became occluded, and gastric or oesophageal transection, although without operative mortality, was often followed by a recurrence of haemorrhage. During the discussion it was agreed that the incidence of hepatoma in cirrhosis was 5-15%. Most speakers were in favour of eliminating alcohol from the diet of all patients with cirrhosis. Dr. Sherlock considered that ascites was a contra-indication to portacaval anastomosis in cirrhosis, but Prof. H. RODGERS preferred to be less dogmatic. Professor Aird thought that improvement after such an operation could often be attributed to the increased collateral circulation which was encouraged. Professor

Aird

was

Radiology

of

Biliary Tract

With Prof. J. MCMICHAEL in the chair, Dr. D. SUTTON spoke on the radiology of the biliary tract. Headvocated the use of the intravenous contrast medium ’Biligrafin,’ especially after cholecystectomy, in preference to the oral method, and he stressed the importance of cho-

langiography during operations involving the biliary tract. Percutaneous trans-hepatic cholangiography in obstructive jaundice was hazardous because of the risk of biliary peritonitis. Dr. Caroli pointed out that biligrafin excretion was related to liver function and, though radiology should always be attempted, serum-bilirubin levels of above 3 mg. per 100 ml. were seldom. compatible with a satisfactory picture.

,

Ascites

In a debate on the problem of ascites in liver disease, Dr. R. 1. S. BAYLISS said that the primary defects of lowered plasma-albumin concentration and increased

860 venous pressure did not alone always explain the accumulation of fluid. Additional factors introduced by the movement of sodium and water into the peritoneal cavity were the diminished output of sodium in urine, sweat, and saliva, possibly associated with increased aldosterone secretion and diminished destruction of other adrenocortical steroids. Altered posterior pituitary antidiuietic-hormone activity and decreased renal bloodflow might, also be of significance. As for treatment, Dr. A. PATON considered that surgical measures designed to reduce portal venous pressure were dangerous, and methods directed at raising colloid osmotic pressure had only a transient effect. The best treatment was paracentesis and then a low-sodium diet (less than 22 m.eq. Na daily), mercurial diuretics, and ammonium chloride. Patients with ascites due to temporary impairment of liver function (alcoholic

portal

.

debauches

or gastro-intestinal haemorrhage) responded rapidly to correction of the precipitating factors, and ascites was controlled in most other’patients by the conservative regime he had outlined. Failure may be liver disease and due to faulty supervision. Active malignanthepatoma were often associated with intractable ascites which resisted treatment and progressed to a terminal dilution hyponatrsemia. During the case demonstrations, it was shown that a good response to treatment was often related to an adequate urinary sodium output in the control period and that relaxation of the regime could sometimes be "

"

allowed without deterioration. Dr. M. D. MILNE advocated a combination of potassium and ammonium chlorides in the treatment of ascites, for mercurial diuretics often caused loss of potassium : and Dr. Bayliss pointed out that altered capillary permeability might be an important factor in the pathogenesis of ascites. Needle Biopsy At this session Prof. L. J. ’WITTS was in the chair. Dr. Sherlock stressed the safety of the procedure (reported mortality 0 17 °,o ) and its wide application in the diagnosis of liver disease, pyrexia of unknown origin, miliary granulomata, reticuloses, and amyloidosis. Dr. C. V. HARRISON exhibited biopsy specimens taken from patients in whom the clinical findings were equivocal and explained the histological criteria upon which the diagnosis was made.

Hepatic Coma Dr. Sherlock described the mental changes and abnormalities of the motor system in hepatic coma. A characteristic electro-encephalogram might be found, but was not specific. Various factors, either affecting liver function adversely or increasing the nitrogenous material in the intestine, might precipitate the disorder. She attributed the syndrome to toxic nitrogenous substances from the portal vein (portal-systemic encephalopathy) and advocated conservative treatment based on the withdrawal of protein, the administration of aureomycin (to reduce bacterial activity in the intestines), and maintenance on glucose. Mr. A. G. RIDDELL also thought that a toxic nitrogenous substance in portal blood was responsible for the neurological disturbance and put forward evidence to incriminate ammonia as the cause in animals and in patients with portacaval anastomoses. He referred to the arrest of haemorrhage by oesophageal tamponage. Dr. Summerskill demonstrated the relationship of the neurological signs to liver function, portal-systemic collateral circulation, and dietary nitrogenous substances. Although many signs of hepatic coma could be induced by nitrogenous substances and improved on protein withdrawal, he hesitated to ascribe the whole syndrome to this cause.

During the discussion, it was shown that methionine might precipitate the neurological syndrome without alteration in blood-ammonia levels and that its adverse effect was retarded by aureomycin. Mr. Riddell had found glutamic acid helpful in patients with chronic signs and portacaval shunts, but it had little effect in It was considered that coma due to liver failure. methionine had no place in the treatment of liver disease. Some Other

Subjects

Colonel W. R. M. DREW considered hepatic arnaebiasis and leptospirosis. both of which were of importance in the ’United Kingdom. The liver was involved in 5-10% of patients with intestinal amoebiasis. Jaundice was rare and he did not believe " hepatitis " occurred, only abscess formation. Radiology was often crucial in diagnosis. Chloroquine was the best drug. Dr. A. E. CLAIREAUX classified the features of neonaittl jaundice as non-obstructive, in which haemolysis and inability of the liver to deal with products of hsemolys In the second were of importance, and obstructive. " category he included the "inspissated-bile syndrome" (which might occur in several diseases) and hepatitis, but he agreed that the classification was not rigid. The differential diagnosis of congenital obliteration of the bile-duct and viral hepatitis was difficult. There was a growing awareness of hepatitis, possibly associated with a carrier state in the mother, as a cause of jaundice in the neonatal period. Dealing with the clinical aspects of neonatal jaundice, Dr. J. W. GERRARD said prognosis was difficult and biliary obstruction was sometimes compatible with a long course, with xanthomatosis and hypercholesterolaomia. He mentioned two interesting dental manifestations-green milk teeth due to deposition of bile in the dentine and enamel hypoplasia due to poor calcification. Jac->t7-ice d1l,rÙlg pregnancy. said Dr. Martini, was either jaundice of pregnancy, a relatively uncommon occurrence in toxaemia and associated with only slight bilirubimemia, or jaundice in pregnancy. This was usually due to viral hepatitis and, contrary to accepted views, was seldom a severe illness, although fmtal mortality and miscarriage were common in the later stages of pregnancy. Jaundice due to gall-stones might also arise during pregnancy. Dr. Y. R. PITNEY, discussing coagulation defects in liver disease, explained that capillary function, platelets, and plasma coagulation factors may all be affected in liver disease. The commonest defect involved the prothrombin complex (prothrombin and factors v and vii) and separate assayswere often desirable because the Quick one-stage prothrombin-time was relatively insensitive to the abnormal prothrombin levels which might occur in all types of liver disease. Dr. Caroli showed an excellent film in which perfusion of the gall-bladder was used to demonstrate changes in tone of the sphincter of Oddi. Reflux into the panereatic duct occurred in response to fatty meals, high perfusion pressures, or atropine. Morphine prevented reflux at high perfusion pressures. Surgical measures designed to correct " hypertrophy " of the sphincter were therefore useless. Professor McMichael said that slight elevation of serum-bilirubin levels was common in heart-failure and that " cardiac cirrhosis " (with deranged liver-function tests) might occur, especially with tricuspid incompetence. Jaundice may be severe, and luemolysis from pulmonary infarcts may be one cause. Dr. Sherlock demonstrated cases of hce-naoclarovzatosis and stressed the family history, the occurrence in males, the alteration in testicular function, and the incidence of cirrhosis ,and hepatoma.. She recommended veneml. weekly) torempve iron from the body, section with careful observation of haemoglobin and; plasma"

"

(500

861 and insulin were valuable supplements..z. Dr. Milne, discussing hepatolenticular degeneration, pointed out that this condition could be distinguished from chronic portal-systemiè encephalopathy by the recessive inheritance, the age-incidence, the absence of fluctuation in the signs, the Kayser-Fleischer rings, the amino-aciduria, and the abnormal copper metabolism (low serum-copper and high’urinary copper values). A specific defect of cseruloplasmin allowed unstable copper to be deposited in the tissues and this produced the

protein valuer. TestQsterone implants

Public Health MALIGNANT DISEASE OF THE RESPIRATORY SYSTEM A STATISTICAL SURVEY

F. L. BRADSHAW

clinical features of the disease. Copper could not be excluded from the diet but potassium sulphide diminished The best treatment was dimercaprol, absorption. potassium sulphide, and a high-protein diet, and this might prevent deterioration in asymptomatic cases. Summing up, Professor McMichael said he was always interested in those points which failed to conform to an accepted theory, for he felt that they often held vital clues. The conference had been a success, and he referred particularly to the considerable contributions by Dr. Sherlock.

1952, using figures for selected years only. Population statistics between 1940 and 1948 were disturbed by the war, and accordingly it seemed better to use figures for three of the early years of the period, and those for the last five years. These, together with figures for two years in the middle of the period, provide a reasonably accurate picture of the general trend between 1932 and 1952. COMPARISON WITH OTHER DISEASES

F.I.A.

THIS survey was prompted by Dr. Evarts Graham’s recent lectureon the aetiology of Bronchogenic Carcinoma. He based his observations largely on statistical material obtained in the United States, and it seemed likely that a similar study of statistics for England and Wales might give rather different results, since the average age of our population is appreciably greater. All the figures are taken from part i of the RegistrarGeneral’s annual statistical reviews. Descriptions of cancer-i.e., malignant neoplasms-and the six broad classifications of its sites, are those given in the review for 1952. The survey covers the twenty-year period 19321.

Graham,

E. A.

Fig. 1 shows the number of deaths per 100,000 of the male population of England and Wales, from cancer and certain diseases of the respiratory system. The latter

Lancet, 1954, i, 1305.

Fig. 2-Deaths

per 100,000 population in England and Wales from malignant neoplasms in 1952 (by age-groups). (A = other unspecified sites ; B=Iymphatic and haematopoietic tissues.)

Fig.

<—Deaths

per

100,000

malignant neoplasms 1932

to

1952.

population in England and Wales from and diseases of the respiratory system from

are shown so as to bring the graph broadly into line with that in Dr. Graham’s fig. 1. The different agedistribution in this country explains why our deathrates are very much higher than those of the United The fall in the death-rate for respiratory States. tuberculosis from over 80 to 30 roughly corresponds to that in the United States. The curve relating to pneumonia, influenza, and bronchitis is difficult to interpret owing to its violent fluctuations, yet here too there has undoubtedly been a fall though a very much smaller one than in the United States. The curves for malignant neoplasms show that the steepest rise in death-rates has been in cancer of the respiratory system. Cancer of the digestive organs is, however, still the greatest destroyer of life. Cancer oi the breast and of the genito-urinary organs shows a steady. increase, and cancer of other and unspecified