Br. J. Surg. Vol. 62 (1975) 701-706

Prognosis after portocaval anastomosis : a 15-year follow-up R . W I N D L E A N D J. H . P E A C O C K * SUMMARY

A 15-year follow-up of 57 patients who underwent portocaval anastomosis is reported. Twenty-seven patients were still alice and the progress of these and of those who died is followed. The young cryptogenic cirrhotic with no errcephalopathy, normal liver function tests and absence of portal vein mural thrombus at the time of operation is best benefited. The only factor from the series to suggest a poor prognosis is deterioration in liver function in the postjuundice cirrhotic, and the development of encephalopathy in cryptogenic cirrhotics suggests a poor long term prognosis, but its onset is not related to the time before death.

portal vein was demonstrated by percutaneous splenoportography (Walker et al., 1953), and in those who had previously had a splenectomy by operative portal venography . The aetiology of the liver disease in the majority wii\ unknown (Table I ) . There were 35 males and 22 females, their ages ranging from 7 to 57 years (averagc 33 years) at the time of operation (Fig. 1).

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CIRRHOSIS, by distortion of the intrahepatic portal vascular bed, gives rise to portal hypertension, and the portal flow through the liver is reduced to 13 per cent (McIndoe, 1928); the rest bypasses the liver along natural portal-systemic anastomoses, one existing in the lower oesophagus between branches of the Ieft gastric vein and those of the azygos, intercostal and diaphragmatic veins. Haemorrhage from varicosities in these veins in the oesophageal wall in portal hypertension accelerates death in 30 per cent of cirrhotics (Truelove, 1972), and the immediate mortality of bleeding has been stated to be as high as 54 per cent (Hislop et al., 1966). Portocaval anastomosis should relieve the portal hypertension with usually minimal but unpredictable deterioration in hepatic function, depending on the reduction in hepatic blood flow following the operation (Nardi, 1955; McDermott, 1965). Portocaval anastomosis has been performed in Bristol for intrahepatic portal obstruction since 1950. This report is concerned with the patients in whom the operation was performed more than 15 years ago in order to ascertain the late effectiveness of anastomosis in stopping bleeding and the resultant side effects.

Patients During the period 1950-7, 57 patients underwent end-to-side anastomosis of the portal vein to the inferior vena cava at Bristol Royal Infirmary for portal hypertension secondary to intrahepatic disease. Virtually all had experienced one or more severe haematemeses, 2 patients had asymptomatic varices and another had presented with associated iron deficiency anaemia. All had been shown to have oesophageal varices on barium swallow studies or oesophagoscopy, and after 1952 the patency of the

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m a

L

0

Z

EEL 0-10

I 1-20

31-40

41-50

5 1-60

Age (yr)

Fig. 1. Age at operation.

Table I : AETIOLOGY OF THE CIRRHOSIS Aetiology : Unknown (cryptogenic) No. of cases: 3 h ) Post-jaundice 1, Alcoholic I Bilharzia I Wilson’s disease 7 Primary portal fibrosis Total

5’

Selection of patients for operation was on age-all the patients submitted to operation being under 60 years of age-the absence of clinical jaundice and ;I serum albumin of greater than 3 g j l 0 0 ml, regar&\\ of other biochemical data. The operative technique has been descri bcd (Walker, 1959); operative saline manometry of thc portal vein pressure was performed, and if infr:rportal mural thrombus was found it was removed unless endothelialized and the lumen adequate.

* Department of Surgery, Royal Infirmary, Bristol. Present address of R. Windle: The Radcliffe Infirmary, Oxford 70 I

R. Windle and J. H. Peacock Table 11: OUTCOME IN PATIENTS WITH THROMBUS IN THE PORTAL VEIN Outcome No. of cases Thrombus in portal vein at operation 10 Thrombus excised 8 Non-survivors 7 Hepatic failure, patent shunt 3 Haemorrhage and coma, thombosed shunt 1 3 Unrelated cause, thrombosed shunt Survivors 3 No further haemorrhage 2 Recurrent haemorrhage 1 Table 111: AVERAGE AGE AT OPERATION Aetiology

Survivors

Total Cryptogenic group Post-iaundice erouo

26.7 27.8

Age (yr) Non-survivors 36.8 38.5 30.5

Table IV: CAUSE OF DEATH IN OPERATWE SURVIVORS Cause of death: Hepatic failure No. of cases: 17 Recurrent haemorrhage 2 Unrelated 6 Table V: GRADE OF SEVERITY OF POSTOPERATIVE SYMPTOMS AT 15 YEARS Total Cryptono. of genic Alcoholic Grade cases group group Symptoms: None Bleeding: None Work : Full

17

16

1

Symptoms : Minimal Bleeding: None Work: Full Occasional visits to doctor

5

4

1

Symptoms : Troublesome Repeated visits to doctor Occasional hospital admissions Work: On and off

2

1

I

Symptoms : Severe Work: None No liver failure

1

1

0

Table VI: FURTHER HAEMORRHAGE Cause No. surviving Fatal haemorrhage Recurrent varices Ishunt thrombosis Peptic ulcer Unknown

2

2*

2

1

1

* One operative death. Table VII: OUTCOME IN PATIENTS WITH PEPTIC ULCERATION Outcome: Clinically healed no treatment No. of cases: 2 Radiologically healed no 2 treatment Healed after vagotomy and 2 drainage Fatal haemorrhage 2* -

Total

* One died at 702

18 years.

8

Results Four patients died in hospital in the postoperative period, an operative mortality of 7 per cent. Three of these patients died from hepatic failure and the remaining patient, in whom thrombus had been removed from the portal vein at operation, developed thrombosis of the shunt and died from further haemorrhage. Ten patients had thrombus in the portal vein at operation (Table 11); 4 of these developed proved shunt thrombosis and another patient had probable shunt thrombosis during the period of follow-up. Twenty-five patients have subsequently died and one is untraceable, leaving 27 patients alive at 15 years (48.2 per cent). Of these, a further 5 have died between 15 and 20 years (2 of liver failure and one each from myocardial infarction, bleeding peptic ulcer and nephrotic syndrome) and are counted alive in this series. Four patients are alive and perfectly well at 21 years. The age of the survivors at operation was 10.1 years younger than that of the non-survivors (Table IZI). Preoperatively the average serum bilirubin levels of the operative non-survivors, 15-year non-survivors and 15-year survivors were 0.5, 0.7 and 0.5 mg/100 ml respectively. One patient who was alive at 15 years had a level raised above normal preoperatively, but 8 patients who died within 15 years of the operation had abnormally raised serum bilirubin levels. Average serum alkaline phosphatase levels were 18 King Armstrong units/100 ml for the group of operative non-survivors, 14.5 King Armstrong units/100 ml for the group of 15-year non-survivors and 11.5 King Armstrong units/100 ml for the group of 15-year survivors. Four patients in the last group had abnormally raised levels preoperatively, whereas 7 in the group of patients not surviving to 15 years had abnormally raised levels. As stated before, all the patients had serum albumin levels greater than 3 g/100 ml and there was no significant difference in the albumin levels of the three groups. In 68 per cent of the non-survivors the cause of death was hepatic failure (Table ZV). Portal-systemic encephalopathy has occurred in 21 of the operative survivors (38 per cent), 13 having since died, but only 2 of these 13 were unable to work after the operation. Only patients over the age of 30 years at the time of operation were affected by encephalopathy prior to their terminal illness. At the time of follow-up 2 were unable to work due to encephalopathy; the other 6 had experienced mild bouts but 3 of them were totally free of encephalopathy when seen (Table V ) . Ten patients (19 per cent) developed encephalopathy within 5 years of the operation, and a further 8 did so in the next 5 years. Unfortunately many of the patients were given high protein diets during the early postoperative phase. This was revised when it became known that such diets predisposed the patients to portal-systemic encephalopathy. Further haemorrhage has occurred in 8 patients, causing I operative and 2 later deaths (Table VI). The 2 patients who survived bleeding from recurrent

Prognosis after portocaval anastomosis varices had both undergone splenectomy prior to the shunt and were treated by oesophageal transection. Neither has bled since and one has no demonstrable varices at 15 years. One non-survivor had asymptomatic varices demonstrated at autopsy. Seventeen of the survivors who had not had further haemorrhage have been checked radiologically or by oesophagoscopy for varices, which have been found in 2. Peptic ulceration has been demonstrated in 8 patients, of whom 2 had ulcers preoperatively, giving a post-shunt incidence of 12 per cent (Table VH). Five patients have developed diabetes mellitus and 2 haemochromatosis since operation. No operative survivors had any significant anaemia, neutropenia or thrombocytopenia. Considering the results in each aetiological group, 22 of the 34 patients with cryptogenic cirrhosis who survived the postoperative period (64 per cent) were

alive at 15 years. Eight died of hepatic failure, their liver function deteriorating as shown in Figs. 2 and 3. and one each of respiratory complications, pyosalpinx. peptic ulcer haemorrhage and cardiac failure. The deaths were evenly distributed over the 15 years since operation (Figs. 4,5 ) , and their relationship to the age at operation is shown in Table VIII. Ten of these non-survivors had experienced bout; of encephalopathy but all but 2 had been able to work after the operation. Of the 22 survivors with cryptogenic cirrhosis, all but one (with gross encephalopathy) were working at 15 years (Table V ) ,2 had mild encephalopathy but a total of 16 had experienced no postoperative encephalopathy. Of these 22 patients, the liver function tests showed no change after operation in 9, deterioration with subsequent recovery in 6 and deterioration without remission in 5 (Fig\ 2, 3); there was insuffcient data on the remaining 2.

a

5

Post-jaundice fptogenic non-survivors , -

4 Cryptogenic survivors

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2

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0

I I

II

5

4

3

2

1

9

Years Fig. 2. Time between onset of irreversible liver decompensation and death o r time of follow-up.

Post-jaundice Cryptogenic non-survivors

0Cryptogenic survivors 2 v m

a, c

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a

% ' 0

Z

2

3

4

Fig. 3. Time between operation and onset of

5

6

10

II

12

13

14

15

Years after operation liver decornpensation.

703

R. Windle and J. €3. Peacock All 9 patients with a history of jaundice prior to their cirrhosis were dead by 1 3 years (Fig. 4). At operation they were between 19 and 55 years old (average 39.5). Five patients died of liver failure, and the others of bleeding varices, aortic aneurysm, carcinoma of the pancreas and suicide. The relationship of survival to age at the time of operation is shown in Table VIII, and the relationship of liver failure to the operation and to subsequent death in Figs. 2 and 3. Only 2 patients had encephalopathy at any time prior to the terminal illness and 6 patients could work after their operation. Six patients had a history of excessive alcohol intake. One was untraceable, one died of liver failure in the first year and one continued drinking and died of liver failure in the third year after operation. Three are still alive; one now incapacitated by encephalopathy, one having mild encephalopathy and fluctuating liver function tests which were normal at the time of follow-up and one with neither encephalopathy nor liver decompensation (Table V ) . The latter 2 still appear to be drinking alcohol. The patient with bilharzia had normal liver function at 15 years but was developing nephrotic syndrome (from which he has since died). One patient with Wilson's disease died of liver failure at 3 years, and of the 2 with portal fibrosis, one died at 6 years after operation and the other is alive and well.

Table VIII: RELATIONSHIP OF SURVIVAL TO AGE AT OPERATION Age at operation (yr) Group 11-20 21-30 31-40 41-50 51-60

.-

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Discussion Without operative intervention, up to 63 per cent of adults bleeding from oesophageal varices will bleed again during the first year of follow-up (Sherlock, 1964). In 15 years of follow-up, 4 (7 per cent) of our patients have had further bleeding owing to recurrent varices after the shunt operation. Of the 4 , 2 have been controlled by further surgery to the oesophagus. Forty-eight had no recurrent haemorrhage, and of these, 40 came to autopsy or were investigated to see whether they had recurrence of oesophageal varices. These were found in 3 patients, giving a total recurrence rate of 12 per cent in the 48 patients investigated. The problems that portocaval anastomosis creates for the patient are well known. Other than an increase in the burden of hepatic decompensation, portosystemic encephalopathy, diabetes mellitus and peptic ulceration as well as other less common problems including haemosiderosis and pulmonary complications can occur (Grace and B a h t , 1966; Sherlock et al., 1970). The operative mortality of 7 per cent in this series is within that quoted by Sherlock (1971) of 5 per cent and by Hunt (1967) of 8 per cent for elective portocaval anastomosis, in distinction to the much higher figure of 25 per cent (Sherlock, 1971) for emergency portocaval anastomosis. Portal-systemic encephalopathy, widely quoted as the major limiting factor in the success of portocaval anastomosis, occurs in as many as 48 per cent of patients to a measurable degree (Sherlock et al., 1970)

0 Cryptogenic Jaundiced

401

201

Cryptogenic cirrhosis Total No. alive a t 5 yr No. aliveat 10yr No. alive a t 15 yr

l!!

Post-jaundice cirrhosis Total No. alive at 5 yr No. alive at 10 yr No. alive at 15 yr

Years after operation

Fig. 4. Proportion of operative survivors against time.

5

5 5 4

1 0 0 0

13 12 12 11

13 9 9 8

2 2 0 0

1 0 0 0

5

2 0 0 0

4

3 0 3 1 1 0

2 1

0 0

Post-jaundice

0

Cryptogenic

2-

F

-

G?

L w

D aJ L

0 1 -

-

0

Z

I

1

Years after operation

Fig. 5. Number of deaths of patients from hepatic failure per year after operation.

704

I

Prognosis after portocaval anastomosic and to a severe degree in from 15 per cent (Grace et al., 1966) to 37 per cent (Read et al., 1961). Of the 53 operative survivors, 21 patients (38 per cent) developed portal-systemic encephalopathy, the onset being distributed over the 15 years following surgery with a predominance during the first 5 postoperative years. However, only 4 (8 per cent) were persistently kept from working by it. Portal-systemic encephalopathy was a worse problem in the cryptogenic cirrhotic group, 47 per cent of which developed the complication, as opposed to the older post-jaundice cirrhotic group of which only 28 per cent developed encephalopathy prior to their terminal illness. This does not agree with our observation or that of others (Read et a]., 1961) that portal-systemic encephalopathy occurs more often in higher age groups, and suggests that portal-systemic encephalopathy and liver biochemistry deterioration do not occur together in the postjaundice group. Sixty-eight per cent of our patients died of hepatic failure. Eight of the 34 patients with cryptogenic cirrhosis died of liver failure, with a further 5 showing deterioration of liver function. The onset of liver failure began at a variable period postoperatively but in 75 per cent it became manifest during the first 6 years. A greater proportion (5 out of 9) of postjaundice cirrhotic patients died of hepatic failure, 60 per cent of them developing it within 2 years of the operation. This deterioration of liver function in the early years after portocaval anastomosis has been observed previously by Sherlock et al. (1970) and demonstrates what is often the progressive nature of cirrhosis following hepatitis. In predicting the patients best benefited by portocaval anastomosis it is considered that the younger the patient and the less the hepatic decompensation, the better is the prognosis postoperatively, jaundice, low serum albumin and portal-systemic encephalopathy being contraindications to the operation (Sherlock, 1964). The young cryptogenic cirrhotic was best benefited in our series; 82 per cent of those under 30 years at operation were alive at 15 years, while none of the patients over 40 years at operation was alive at 15 years (Table VIII). The patients who had postjaundice cirrhosis and who were of ages comparable to the non-surviving group of cryptogenic cirrhotics did no better, all dying by 13 years after the operation. The patients with alcoholic cirrhosis, who usually progress well after the operation if drinking is stopped (Sherlock, 1971), did well in the small series we present here, 3 out of 5 patients being alive at 15 years and the 2 least incapacitated by encephalopathy still drinking alcohol. However, of 15 patients, all alcoholic cirrhotics, who have undergone portocaval anastomosis since 1957 in Bristol, 11 are traceable and 9 of these have died of liver failure within 5 years of operation. Patients with any degree of liver decompensation are not usually submitted to elective portocaval anastomosis, and it can be seen from our series that the patients with an abnormally raised serum bilirubin level have not progressed as well as those with normal 51

bilirubin levels. Abnormally raised alkaline phosphatase levels in the serum appear to be of les\ significance. Patients who had thrombus in the portal vein ai operation did not progress well after the operation; 30 per cent were alive at 15 years and 80 per cent of them had rethrombosis of the shunt. This even applied when the thrombus was easily removed from the portal vein at operation. The progress of the patient after his portocaval anastomosis allowed some prediction of his ultimate prognosis. If the patient had further haemorrhage, whether this was associated with shunt thrombosis or with a peptic ulcer, the problem was serious and even haemorrhage from peptic ulcer had a mortality of 33 per cent. Deterioration in liver function heralded a rapid deterioration in the patients who had postjaundice cirrhosis, and commonly, but not as often, in the patients with cryptogenic cirrhosis. However, portal-systemic encephalopathy had a prognostic significance only in the patients who had cryptogenic cirrhosis, as 10 of the 12 operative survivors i n the latter group who were dead by 15 years had portal-systemic encephalopathy, but there was little relationship to time, as those with portal-systemic encephalopathy at 10 years were all alive at 15 years.

Acknowledgements We acknowledge with gratitude the fact that these patients are the original series of Professor R. Milnes Walker (Walker et al., 1961). We also acknowledge the help of Dr P. D. Mulcahy, Dr G . M. Colson, Dr J. N. MacCaig, Dr P. J . Toghill and Dr M. J. Whelton in tracing and arranging investigations on their patients included in this series. References and BALINT J. A. (1966) Haemochromatosi\ associated with end to side porto-caval anastomosis. Am. J . Dig. Dis., 11, 351-358. GRACE N. D., MUENCH H. and CHALMERS T. c. (1966) The present status of shunts for portal hypertension in cirrhosis. Gastroenterology 50, 685-691. HlSLOP I. G., WATERS T. E., KELLOCK T. D. and S W Y N N E R T ~ N B. (1966) The natural history of haemorrhage from oesophageal varices. Lancet I , 945-948. HUNT A. c. (1967) Observations on the treatment and prognosis of portal hypertension. In: READ A. t. (ed) The Liver, Proceedings of the Nineteenth Symposium of the Colston Research Society, Bristoll967. London, Butterworths, pp. 371-375. MCDERMOTT w. v. jun. (1965) The techniques of portalsystemic shunt surgery. Surgery 57, 778-786. MCINDOE A. H. (1928) Vascular lesions of portal cirrhosis. Arch. Pnthol. 5 , 23. NARDI G. L. (1955) Effects of spleno-renal shunts on hepatic blood flow. Arch. Surg. 70, 530-534. READ A. E., LAIDLAW J. and SHERLOCK s. (1961) Neuropsychiatric complications of porto-caval anastomosis. Lancet 1, 961-963. GRACE N. D.

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R. Windle and J. N. Peacock s. (1964) Haematemesis in portal hypertension. Br. J. Surg. 51, 746-749. SHERLOCK s. ( 1 9 7 1 ) Diseases of the Liver and Biliary System, 4th ed. Oxford, Blackwell, pp. 1 6 5 - 2 2 7 . SHERLOCK s., GEORGE P. and HOURIGAN K. ( 1 9 7 0 ) Medical complications of shunt surgery for portal hypertension. Ann. N Y Acnd. Sci. 170, 392405. TRUELOVE s. C. ( 1 9 7 2 ) Diseases of Digestive System, 2nd ed. Oxford, Blackwell, pp. 6 0 8 - 6 1 3 . SHERLOCK

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(1959) Pathology and Management of Portal Hypertension. London, Arnold, p. 67. WALKER R . M., MIDDLEMISS J. H. and NANSON E. M. (1 953) Portal venography by intra-splenic injection. Br. J. Surg. 40, 392-395. WALKER R . M., SHALDEN c. and VOWLES K . D. J. ( 1 9 6 1 ) Late results of porto-caval anastomosis. Lancet 11, 7 2 7 - 7 3 0 . WALKER R . M.