655
changes in the T metaboencountered in serum T.s.H. levels. Although one would expect an initial increased serum T.s.H. due to low serum T3, it had a tendency to be lower during the acute stage of disease and increased slightly with recovery. These changes were not signifi-
In contrast to these lites very little change
cant
acute was
(table n). Discussion
study confirms the earlier findings of important T3 reductions in many diseases.s-1o These results are of clinical importance: the patients described were not severely ill. Nevertheless in three cases out of eight the serum T3 levels were initially in the hypothyroid range. Obviously, on the basis of the clinical history and the normal serum T and c.s.H.levels, the diagnosis of hypothyroidism could easily be rejected. For practical purposes it is therefore important to realise that the normal range of serum T3 levels is valid only for healthy euthyroid subjects. When investigating for hypothyroidism in sick patients this test should not be used, while serum T4 in conjunction with direct or indirect measurements (T3 resin uptake) of its free fraction can be regarded as reliable. Reverse T3, like T3, has three iodine atoms but monodeiodination of T4 occurs on the inner or tyrosine ring, while for T3 the monodeiodination occurs on the outer ring. This difference makes reverse T3 calorigenically inactive.’9 The pathway from T4 to reverse T3 therefore represents an inactivation, contrasting with the activating pathway from T4 to T3. On the other hand, tetrac is formed by conversion of the alanyl side chain of T44 The present serum
to an
acetic-acid
residue, without deiodination. Tetrac is
calorigenic and has been used in substitution treatment of patients with myxaedema.2O Yet on a molar basis, it is approximately ten times less active than T4, even though its cholesterol-lowering effect may be more pronounced.21 The results can be summarised as follows: during the stage of the disease, there is a reduction of all active thyroid hormones: serum T3’ tetrac, and, non-significantly, T4. As T3 is mainly and tetrac exclusively a product of the peripheral metabolism ofT4, one can condude that during the acute catabolic state of disease the production of active metabolites from T4 is diminished, while with convalescence the levels of these metabolites rapidly recover. However, T4 metabolism is not generally depressed. During acute disease there is a substantial increase in inactive reverse T3 which at least partially compensates for reduced transformation of T44 into T3 and tetrac. These peripheral changes in thyroid hormones are but one aspect of a thyroidal adaptation to acute disease. The absence of T.S.H. changes in response to low serum T3 shows that hypothalamic adaptations must also
by limitation of the hypermetabolic state. A better understanding of the patho-physiological control mechanisms would therefore be welcome, particularly in view of the metabolic importance that these hormonal changes could have in many diseases. illness
This work was supported by the Fonds National Suisse de la Recherche Scientifique grants no. 3.799.72 and 3.516.75 and by the National Institute of Health, grant no. AM 08919. We thank the staff of the Department of Internal Medicine who collaborated in the study; Miss H. Steinhart and Mrs Th. Burer for their excellent technical assistance; and Mr J. Jackson for his help in preparing the manuscript. Requests for reprints should be addressed to A. B., Laboratoire d’Investigation clinique, Hopital cantonal, CH-1211 Geneva 4, Switzerland. REFERENCES
1. De Rubertis, F. R., Kosch, Ph.C. J. clin. Endocr. Metab. 1975, 40, 589. 2. Wartofsky, L., Martin, D., Earll, J. M. J. clin. Invest. 1972, 51, 2215. 3. Woeber, K. A. ibid. 1971, 50, 378. 4. De Rubertis, F. R., Woeber, K. A. ibid, 1973, 52, 78. 5. Chopra, I. J., Chopra, U., Smith, S. R., Reza, M., Solomon, D. H. J. clin. Endocr. Metab. 1975, 41, 1043. 6. Vagenakis, A. G., Burger, A., Portnay, G. I., Rudolph, M., O’Brian, J. T., Azizi, F., Arky, R. A., Nicod, P., Ingbar, S. H., Braverman, L. E. J. clin. Endocr Metab. 1975, 41, 191. 7. Chopra, I. J., Smith, St.R. ibid. 1975, 40, 221. 8. Ingenbleek, Y., Beckers, C. Lancet, 1975, ii, 845. 9. McLarty D. G., Ratcliffe, W. A., McColl, K., Stone, D., Ratcliffe, J. G. ibid.
p. 275. Burr, W. A., Griffiths, R. S., Black, E. G., Hoffenberg, R., Meinhold, H.,
10. 11.
12.
13. 14. 15.
Wenzel, K. W. ibid. p. 1277. Burger, A. in Clinical Biochemistry: Pnnciples and Methods, (edited by H. Ch. Curtius and M. Roth); p. 881. Berlin, 1974. Burger, A. Sakoloff, C., Staeheli, V., Vallotton, M. B., Ingbar, S. H. Acta endocr. Copenh. 1975, 80, 58. Nicod, P., Burger, A., Staeheli, V., Vallotton, M. B. J. clin. Endocr. Metab. (in the press). Burger, A., Sakoloff, C. Unpublished. Odell, W. D., Wilber, J. F., Utiger, R. D. Rec. Prog. Horm. Res. 1967, 23, 47.
Roberts, R. C. Nicolai, T. F. Clin. Chemistry, 1969, 15, 1132. Oppenheimer, J. H., Martinez, M., Bernstein, G. J. Lab. clin. Med. 1966, 67, 500. 18. Nauman, J. A., Nauman, A., Werner, S. C. J. clin. Invest. 1967, 46, 1346. 19. Pittman, J. A., Brown, R. W., Register, H. B. Endocrinology 1962, 70, 78. 20. Rall, J. E., Pearson, O. H , Lipsett, M. B., Rawson, R. W. J. clin. Endocr. Metab. 1956, 16, 1299. 21. Lerman, J. ibid. 1961, 21, 1044. 22. Bray, G. A. Lancet, 1969, ii, 397. 16. 17.
acute
occur.
Very little is known about control mechanisms responsible for these hormonal changes. It is likely that they are related to energy balance as indicated by studies on calorie restriction.6 In this situation the organism can rapidly reduce its metabolic rate, while serum T3 deand reverse T3 increases.22 The reduction of thyroid hormones may therefore represent an adaptive mechanism to limit catabolism-in the case of starvation by reduction of basal metabolism and during
creases
active
A CONTROLLED STUDY OF THERAPEUTIC PORTACAVAL SHUNT IN ALCOHOLIC
CIRRHOSIS DANIELLE PRANDI JACQUELINE SICOT C. SICOT R. FAUVERT J.-P. BENHAMOU
B. RUEFF FRANCOISE DEGOS J.-D. DEGOS J.-N. MAILLARD Service
d’Hépato-Gastroentérologie, Unité de Recherches de Physiopathologie Hépatique (INSERM), and Clinique Chirurgicale, Hôpital Beaujon, 92110 Clichy, France
A controlled study of therapeutic end-toside portacaval shunt was carried out from 1968 to 1971 in 89 patients with alcoholic cirrhosis. Recurrent gastrointestinal bleeding was less common and chronic hepatic encephalopathy was more common in patients with shunts than in patients without shunts. The survival-rate was lower, but not significantly, in patients with shunts. No overall benefit of the operation could be demonstrated in cirrhotic patients with the selection criteria and the type of surgical shunt used in this study.
Summary
656
Introduction
TABLE 1--CLINICAL DATA
FROM 1945 to 1970, portacaval shunt was accepted as beneficial in cases of portal hypertension due to cirrhosis. This conclusion was based on many uncontrolled or poorly controlled, studies.’ Controlled studies have shown that a prophylactic shunt-i.e., one performed in subjects who have not yet bled-is of no benefit to cirrhotic patients .2 The benefit of a therapeutic shunt-i.e., one performed in cirrhotic patients having had one or several episodes of gastrointestinal bleeding -is controversial. There have been three controlled studies of therapeutic portacaval shunt. Results from two of these studies-the Veterans Administration Cooperative (V.A.C.) study3 and the Boston Inter-hospital Liver Group (B.I.L.G.) study4-are definitive, but results of the third study5 are only preliminary. We report the results of a controlled study of therapeutic end-to-side portacaval shunt in patients with alcoholic cirrhosis and compare these results with those of the three studies mentioned above.
Patients and Methods Criteria for selection were as follows: (1) cirrhosis established by peritoneoscopy and/or biopsy; (2) cirrhosis thought to result from alcoholism-i.e., daily alcohol intake of 150 g or more for five years or more and no other cause of liver disease ; (3) at least one episode of gastrointestinal bleeding requiring blood-transfusion of 800 ml or more within the first twenty-four hours; (4) gastrointestinal bleeding controlled by medical treatment6 for at least two weeks in patients who were not operated upon and until surgery in those who were; (5) no liver failure or only mild liver failure in most patients (the
TABLE II-LABORATORY FINDINGS
*Median. tRange of the 95% confidence interval calculated after of the data.
logarithmic comcrm
degree of liver failure was assessed according to the absence or presence before the episode of bleeding of (a) serum-bilirubin higher than 4 mg/dl, (b) ascites, (c) hepatic encephalopathy, (d) weight-loss greater than 15% of body-weight (liver failure was regarded as being absent or mild when none or only one of these disorders was present, and severe when two disorders or more were present); (6) cesophageal or gastric varices demonstrated by X-ray and/or endoscopic examination; (7) patients with peptic ulcer were excluded. Out of 300 cirrhotic patients with gastrointestinal bleeding admitted to Hopital Beaujon from 1968 to 1971, 89 met these criteria and
randomly assigned to two groups (see accompatients were assigned to the non-surgtcal or control group and 40 to the surgical group. Among the patients assigned to the surgical group, 9 were not given shunts for the following reasons: thrombosis of the portal vein (2), intercurrent disease after randomisation (2), patient’s refusal (5). These 9 patients constituted the exclusion group. 31 patients in whom end-to-side portacaval shunt was performed constituted the shunt group; the interval from bleeding to surgery ranged from four to fourteen days (mean, seven). Characteristics of patients in the different groups are given in tables were
panying figure).
49
and u. The patients were re-examined at least once a year. Follow-up lasted three years or more in all patients. 3 patients were lost to follow-up, but information about date of death was available. Recurrent bleeding in patients in the control group was treated as follows: in patients with bleeding uncontrolled by medical treatment and with no or mild liver failure emergency end-to-side portacaval shunt was performed;’ in patients with bleeding controlled by medical treatment or in those with severe liver failure no operation was performed whatever the number of recurrent episodes of bleeding, Every patient was strongly advised to abstain from alcohol; our impression is that about half the patients gave it up completely. Survival-rates were calculated according to the direct method.8 The percentages were compared using the Z’ test or Fisher’s exact solution test.9 The results presented in table II were compared using the t test after logarithmic conversion of the data. 10 i
Results Shunt
Distribution of patients into groups.
Group
Postoperative mortality.-6 patients died from severe liver failure within a month of surgery; 1 of these patients had hepatorenal syndrome at operation; in 3 patients unsuspected carcinoma (hepatocellular in 2, pancreatic in 1) was discovered at surgery. 25 patients surviving a month or more were called the surviving shunt group.
657 Recurrence of gastrointestinal bleeding.-6 patients in the surviving shunt group had recurrent bleeding. In 2 gastrointestinal bleeding was moderate and was the consequence of erosive cesophagitis in 1 and aspirin-induced erosive gastritis in the other. 4 patients died from massive gastrointestinal bleeding. In one of these 4 patients, necropsy showed that the stoma of the shunt was abnormally narrow, in another a second operation showed both acute duodenal ulceration and portal hypertension (mesenteric venous pressure, 26 mm Hg) related to obstruction of the shunt, and in 2 the stoma of the shunt was patent and bleeding resulted from mul-
tiple gastric erosions. Hepatic encephalopathy.-10 patients in the surviving shunt group had hepatic encephalopathy which started in the first year after shunt in 5 patients and in the second year in the other 5. In 2 of these 10 patients hepatic encephalopathy was associated with other manifestations of end-stage liver failure. In 2 other patients only one episode of encephalopathy occurred. In the remaining 6 patients encephalopathy persisted for from six months to two years until the patient’s death. We described such encephalopathy as chronic hepatic encephalopathy.
TABLE IV-SURVIVAL-RATES IN SUBGROUPS OF PATIENTS FROM CONTROL
GROUP
Survival-rates
are not
significantly different in the three subgroups.
the study, 23 control patients of death was massive gastrointestinal bleeding and/or postoperative complications after emergency portacaval shunt-in 7, bleeding and severe liver failure in 5, and severe liver failure in 11. At necropsy, in addition to cirrhosis, the following lesions were noted: hepatocellular carcinoma (2); hepatocellular carcinoma and portal-vein thrombosis (1); portal-vein thrombosis (3); pulmonary tuberculosis (1); and hepatic and splenic tuberculosis (1). Survival-rates in the control group and other subgroups are shown in tables in and iv.
Mortality.-During
died. The
cause
Exclusion
Group
signifi-
At the time of this report, 1 patient in the exclusion group who had initially refused surgery insisted on having a portacaval shunt. The other 8 patients were not operated on; 6 of them died. The causes of death were: massive bleeding (2); septicaemia (1); and severe live." failure (3). At necropsy, hepatocellular carcinoma was found in 2 patients in addition to cirrhosis. The course of cirrhosis in patients from the exclusion group resembled that in patients from the shunt and control groups.
Mortality.-During the study, 15 patients in the surviving shunt group died. The cause of death was: massive gastrointestinal bleeding (4); hepatic encephalopathy (5); hepatic encephalopathy and staphylococcal septicaemia (2); intracranial haemorrhage (2); and the cause of death was not known in 2 (these patients died outside the hospital). Necropsy was performed in 11 patients; the shunt was patent in 10 and thrombosed in 1; hepatocellular carcinoma was present in 2; carcinoma of both oesophagus and colon was discovered in 1. The survival-rates of the shunt and the surviving shunt groups are given in table in.
Comparison of Shunt and Control Groups Recurrence of gastrointestinal bleeding.-Significantly fewer patients in the shunt group had recurrent bleeding; 6 out of 25 compared with 36 out of 49 in the control group (P
changes in the T metaboencountered in serum T.s.H. levels. Although one would expect an initial increased serum T.s.H. due to low serum T3, it had a tendency to be lower during the acute stage of disease and increased slightly with recovery. These changes were not signifi-
In contrast to these lites very little change
cant
acute was
(table n). Discussion
study confirms the earlier findings of important T3 reductions in many diseases.s-1o These results are of clinical importance: the patients described were not severely ill. Nevertheless in three cases out of eight the serum T3 levels were initially in the hypothyroid range. Obviously, on the basis of the clinical history and the normal serum T and c.s.H.levels, the diagnosis of hypothyroidism could easily be rejected. For practical purposes it is therefore important to realise that the normal range of serum T3 levels is valid only for healthy euthyroid subjects. When investigating for hypothyroidism in sick patients this test should not be used, while serum T4 in conjunction with direct or indirect measurements (T3 resin uptake) of its free fraction can be regarded as reliable. Reverse T3, like T3, has three iodine atoms but monodeiodination of T4 occurs on the inner or tyrosine ring, while for T3 the monodeiodination occurs on the outer ring. This difference makes reverse T3 calorigenically inactive.’9 The pathway from T4 to reverse T3 therefore represents an inactivation, contrasting with the activating pathway from T4 to T3. On the other hand, tetrac is formed by conversion of the alanyl side chain of T44 The present serum
to an
acetic-acid
residue, without deiodination. Tetrac is
calorigenic and has been used in substitution treatment of patients with myxaedema.2O Yet on a molar basis, it is approximately ten times less active than T4, even though its cholesterol-lowering effect may be more pronounced.21 The results can be summarised as follows: during the stage of the disease, there is a reduction of all active thyroid hormones: serum T3’ tetrac, and, non-significantly, T4. As T3 is mainly and tetrac exclusively a product of the peripheral metabolism ofT4, one can condude that during the acute catabolic state of disease the production of active metabolites from T4 is diminished, while with convalescence the levels of these metabolites rapidly recover. However, T4 metabolism is not generally depressed. During acute disease there is a substantial increase in inactive reverse T3 which at least partially compensates for reduced transformation of T44 into T3 and tetrac. These peripheral changes in thyroid hormones are but one aspect of a thyroidal adaptation to acute disease. The absence of T.S.H. changes in response to low serum T3 shows that hypothalamic adaptations must also
by limitation of the hypermetabolic state. A better understanding of the patho-physiological control mechanisms would therefore be welcome, particularly in view of the metabolic importance that these hormonal changes could have in many diseases. illness
This work was supported by the Fonds National Suisse de la Recherche Scientifique grants no. 3.799.72 and 3.516.75 and by the National Institute of Health, grant no. AM 08919. We thank the staff of the Department of Internal Medicine who collaborated in the study; Miss H. Steinhart and Mrs Th. Burer for their excellent technical assistance; and Mr J. Jackson for his help in preparing the manuscript. Requests for reprints should be addressed to A. B., Laboratoire d’Investigation clinique, Hopital cantonal, CH-1211 Geneva 4, Switzerland. REFERENCES
1. De Rubertis, F. R., Kosch, Ph.C. J. clin. Endocr. Metab. 1975, 40, 589. 2. Wartofsky, L., Martin, D., Earll, J. M. J. clin. Invest. 1972, 51, 2215. 3. Woeber, K. A. ibid. 1971, 50, 378. 4. De Rubertis, F. R., Woeber, K. A. ibid, 1973, 52, 78. 5. Chopra, I. J., Chopra, U., Smith, S. R., Reza, M., Solomon, D. H. J. clin. Endocr. Metab. 1975, 41, 1043. 6. Vagenakis, A. G., Burger, A., Portnay, G. I., Rudolph, M., O’Brian, J. T., Azizi, F., Arky, R. A., Nicod, P., Ingbar, S. H., Braverman, L. E. J. clin. Endocr Metab. 1975, 41, 191. 7. Chopra, I. J., Smith, St.R. ibid. 1975, 40, 221. 8. Ingenbleek, Y., Beckers, C. Lancet, 1975, ii, 845. 9. McLarty D. G., Ratcliffe, W. A., McColl, K., Stone, D., Ratcliffe, J. G. ibid.
p. 275. Burr, W. A., Griffiths, R. S., Black, E. G., Hoffenberg, R., Meinhold, H.,
10. 11.
12.
13. 14. 15.
Wenzel, K. W. ibid. p. 1277. Burger, A. in Clinical Biochemistry: Pnnciples and Methods, (edited by H. Ch. Curtius and M. Roth); p. 881. Berlin, 1974. Burger, A. Sakoloff, C., Staeheli, V., Vallotton, M. B., Ingbar, S. H. Acta endocr. Copenh. 1975, 80, 58. Nicod, P., Burger, A., Staeheli, V., Vallotton, M. B. J. clin. Endocr. Metab. (in the press). Burger, A., Sakoloff, C. Unpublished. Odell, W. D., Wilber, J. F., Utiger, R. D. Rec. Prog. Horm. Res. 1967, 23, 47.
Roberts, R. C. Nicolai, T. F. Clin. Chemistry, 1969, 15, 1132. Oppenheimer, J. H., Martinez, M., Bernstein, G. J. Lab. clin. Med. 1966, 67, 500. 18. Nauman, J. A., Nauman, A., Werner, S. C. J. clin. Invest. 1967, 46, 1346. 19. Pittman, J. A., Brown, R. W., Register, H. B. Endocrinology 1962, 70, 78. 20. Rall, J. E., Pearson, O. H , Lipsett, M. B., Rawson, R. W. J. clin. Endocr. Metab. 1956, 16, 1299. 21. Lerman, J. ibid. 1961, 21, 1044. 22. Bray, G. A. Lancet, 1969, ii, 397. 16. 17.
acute
occur.
Very little is known about control mechanisms responsible for these hormonal changes. It is likely that they are related to energy balance as indicated by studies on calorie restriction.6 In this situation the organism can rapidly reduce its metabolic rate, while serum T3 deand reverse T3 increases.22 The reduction of thyroid hormones may therefore represent an adaptive mechanism to limit catabolism-in the case of starvation by reduction of basal metabolism and during
creases
active
A CONTROLLED STUDY OF THERAPEUTIC PORTACAVAL SHUNT IN ALCOHOLIC
CIRRHOSIS DANIELLE PRANDI JACQUELINE SICOT C. SICOT R. FAUVERT J.-P. BENHAMOU
B. RUEFF FRANCOISE DEGOS J.-D. DEGOS J.-N. MAILLARD Service
d’Hépato-Gastroentérologie, Unité de Recherches de Physiopathologie Hépatique (INSERM), and Clinique Chirurgicale, Hôpital Beaujon, 92110 Clichy, France
A controlled study of therapeutic end-toside portacaval shunt was carried out from 1968 to 1971 in 89 patients with alcoholic cirrhosis. Recurrent gastrointestinal bleeding was less common and chronic hepatic encephalopathy was more common in patients with shunts than in patients without shunts. The survival-rate was lower, but not significantly, in patients with shunts. No overall benefit of the operation could be demonstrated in cirrhotic patients with the selection criteria and the type of surgical shunt used in this study.
Summary
656
Introduction
TABLE 1--CLINICAL DATA
FROM 1945 to 1970, portacaval shunt was accepted as beneficial in cases of portal hypertension due to cirrhosis. This conclusion was based on many uncontrolled or poorly controlled, studies.’ Controlled studies have shown that a prophylactic shunt-i.e., one performed in subjects who have not yet bled-is of no benefit to cirrhotic patients .2 The benefit of a therapeutic shunt-i.e., one performed in cirrhotic patients having had one or several episodes of gastrointestinal bleeding -is controversial. There have been three controlled studies of therapeutic portacaval shunt. Results from two of these studies-the Veterans Administration Cooperative (V.A.C.) study3 and the Boston Inter-hospital Liver Group (B.I.L.G.) study4-are definitive, but results of the third study5 are only preliminary. We report the results of a controlled study of therapeutic end-to-side portacaval shunt in patients with alcoholic cirrhosis and compare these results with those of the three studies mentioned above.
Patients and Methods Criteria for selection were as follows: (1) cirrhosis established by peritoneoscopy and/or biopsy; (2) cirrhosis thought to result from alcoholism-i.e., daily alcohol intake of 150 g or more for five years or more and no other cause of liver disease ; (3) at least one episode of gastrointestinal bleeding requiring blood-transfusion of 800 ml or more within the first twenty-four hours; (4) gastrointestinal bleeding controlled by medical treatment6 for at least two weeks in patients who were not operated upon and until surgery in those who were; (5) no liver failure or only mild liver failure in most patients (the
TABLE II-LABORATORY FINDINGS
*Median. tRange of the 95% confidence interval calculated after of the data.
logarithmic comcrm
degree of liver failure was assessed according to the absence or presence before the episode of bleeding of (a) serum-bilirubin higher than 4 mg/dl, (b) ascites, (c) hepatic encephalopathy, (d) weight-loss greater than 15% of body-weight (liver failure was regarded as being absent or mild when none or only one of these disorders was present, and severe when two disorders or more were present); (6) cesophageal or gastric varices demonstrated by X-ray and/or endoscopic examination; (7) patients with peptic ulcer were excluded. Out of 300 cirrhotic patients with gastrointestinal bleeding admitted to Hopital Beaujon from 1968 to 1971, 89 met these criteria and
randomly assigned to two groups (see accompatients were assigned to the non-surgtcal or control group and 40 to the surgical group. Among the patients assigned to the surgical group, 9 were not given shunts for the following reasons: thrombosis of the portal vein (2), intercurrent disease after randomisation (2), patient’s refusal (5). These 9 patients constituted the exclusion group. 31 patients in whom end-to-side portacaval shunt was performed constituted the shunt group; the interval from bleeding to surgery ranged from four to fourteen days (mean, seven). Characteristics of patients in the different groups are given in tables were
panying figure).
49
and u. The patients were re-examined at least once a year. Follow-up lasted three years or more in all patients. 3 patients were lost to follow-up, but information about date of death was available. Recurrent bleeding in patients in the control group was treated as follows: in patients with bleeding uncontrolled by medical treatment and with no or mild liver failure emergency end-to-side portacaval shunt was performed;’ in patients with bleeding controlled by medical treatment or in those with severe liver failure no operation was performed whatever the number of recurrent episodes of bleeding, Every patient was strongly advised to abstain from alcohol; our impression is that about half the patients gave it up completely. Survival-rates were calculated according to the direct method.8 The percentages were compared using the Z’ test or Fisher’s exact solution test.9 The results presented in table II were compared using the t test after logarithmic conversion of the data. 10 i
Results Shunt
Distribution of patients into groups.
Group
Postoperative mortality.-6 patients died from severe liver failure within a month of surgery; 1 of these patients had hepatorenal syndrome at operation; in 3 patients unsuspected carcinoma (hepatocellular in 2, pancreatic in 1) was discovered at surgery. 25 patients surviving a month or more were called the surviving shunt group.
657 Recurrence of gastrointestinal bleeding.-6 patients in the surviving shunt group had recurrent bleeding. In 2 gastrointestinal bleeding was moderate and was the consequence of erosive cesophagitis in 1 and aspirin-induced erosive gastritis in the other. 4 patients died from massive gastrointestinal bleeding. In one of these 4 patients, necropsy showed that the stoma of the shunt was abnormally narrow, in another a second operation showed both acute duodenal ulceration and portal hypertension (mesenteric venous pressure, 26 mm Hg) related to obstruction of the shunt, and in 2 the stoma of the shunt was patent and bleeding resulted from mul-
tiple gastric erosions. Hepatic encephalopathy.-10 patients in the surviving shunt group had hepatic encephalopathy which started in the first year after shunt in 5 patients and in the second year in the other 5. In 2 of these 10 patients hepatic encephalopathy was associated with other manifestations of end-stage liver failure. In 2 other patients only one episode of encephalopathy occurred. In the remaining 6 patients encephalopathy persisted for from six months to two years until the patient’s death. We described such encephalopathy as chronic hepatic encephalopathy.
TABLE IV-SURVIVAL-RATES IN SUBGROUPS OF PATIENTS FROM CONTROL
GROUP
Survival-rates
are not
significantly different in the three subgroups.
the study, 23 control patients of death was massive gastrointestinal bleeding and/or postoperative complications after emergency portacaval shunt-in 7, bleeding and severe liver failure in 5, and severe liver failure in 11. At necropsy, in addition to cirrhosis, the following lesions were noted: hepatocellular carcinoma (2); hepatocellular carcinoma and portal-vein thrombosis (1); portal-vein thrombosis (3); pulmonary tuberculosis (1); and hepatic and splenic tuberculosis (1). Survival-rates in the control group and other subgroups are shown in tables in and iv.
Mortality.-During
died. The
cause
Exclusion
Group
signifi-
At the time of this report, 1 patient in the exclusion group who had initially refused surgery insisted on having a portacaval shunt. The other 8 patients were not operated on; 6 of them died. The causes of death were: massive bleeding (2); septicaemia (1); and severe live." failure (3). At necropsy, hepatocellular carcinoma was found in 2 patients in addition to cirrhosis. The course of cirrhosis in patients from the exclusion group resembled that in patients from the shunt and control groups.
Mortality.-During the study, 15 patients in the surviving shunt group died. The cause of death was: massive gastrointestinal bleeding (4); hepatic encephalopathy (5); hepatic encephalopathy and staphylococcal septicaemia (2); intracranial haemorrhage (2); and the cause of death was not known in 2 (these patients died outside the hospital). Necropsy was performed in 11 patients; the shunt was patent in 10 and thrombosed in 1; hepatocellular carcinoma was present in 2; carcinoma of both oesophagus and colon was discovered in 1. The survival-rates of the shunt and the surviving shunt groups are given in table in.
Comparison of Shunt and Control Groups Recurrence of gastrointestinal bleeding.-Significantly fewer patients in the shunt group had recurrent bleeding; 6 out of 25 compared with 36 out of 49 in the control group (P
