Br. J. Surg. 1992, Vol. 79, January, 39-42

B. SUC, Y. Panis, J. Belghiti and F. Fekete Department of Digestive Surgery, Hbpital Beaujon, 921 18 Clichy, France Correspondence to: Professor J. Belghiti

’Natural history’ of hepatectomy The aim of this study was to describe biochemical and liver function test changes after hepatectomy in 33 patients with the following characteristics: absence of underlying liver disease, no blood or plasma transfusion during the perioperative period, uneventful postoperative course. Resection with a temporary pedicle inflow occlusion ( 10-45 min) consisted of unisegmentectomy or less in 15 patients and bisegmentectomy or more in 18. Blood tests showed: a correlation between aminotransferase rise and duration of ischaemia, and a fall in prothrombin time and factor V levels correlating with the weight of resected specimen at day I ;a moderate y-glutamyl transpeptidase and alkaline phosphatase elevation and a rise in Jibrinogen level correlating with the extent o j ~resection at day 7. Changes in haemoglobin level, white cell count, platelet count, prothrombin time, ,factor V level and serum bilirubin level tended to return to preoperative levels by day 7. For y-glutarnyl transpeptidase and alkaline phosphatase, increased levels persisted f o r 8-12 weeks after resection. These results, in this selected group of patients, allow a description of the ‘natural history’ of‘ hepatectomy. The knowledge of these ‘natural’ changes may contribute to the early detection of postoperative complications.

Despite a dramatic decrease in mortality and morbidity rates following hepatic resection during the last 10 years’.’, intra-abdominal sepsis, biliary complications and liver insufficiency remain significant problem^'.^. Diagnosis of these complications requires the collection of clinical, morphological and biological data, including liver function tests. The assessment of tests which aim to evaluate liver function is difficult after hepatic resection. This may be related not only to the extent of the resection and the underlying disease, but also to the volume of blood and plasma transfused5-’. The aim of this retrospective study was to observe changes in liver function tests after uncomplicated hepatectomy in a homogeneous group of patients in whom surgery was performed by the same surgeon using a standard operative procedure and in whom no blood or plasma transfusion was given during the perioperative period. In this study, the postoperative changes in liver function tests might reflect the ‘natural history’ of hepatectomy.

Patients and methods The records of 119 patients undergoing hepatic resection between January 1987 and July 1989 were reviewed. Data were collected on 33 patients who fulfilled the following criteria: n o blood and/or plasma transfusion in the perioperative period, normal residual liver confirmed by surgical biopsy, uneventful postoperative course. There were 27 women and six men with a mean(s.d.) age of 37( 13) years, range 21-76 years. Resections were performed for benign liver cell tumours in 23, and malignant tumours in ten (colorectal metastases in nine and fibrolamellar carcinoma in one). All operations were performed by the same surgeon (J.B.). Laparotomy was by means of a right subcostal incision. Intraoperztive ultrasonography was systematically performed to determine the size and location of the tumour as well as the relationship between the tumour and the vascular system. In all cases the resection was carried out with temporary inflow occlusion of the liver. In cases of major liver resection (including more than two segments) the liver was mobilized to expose the inferior vena cava; extraparenchymatous control of both arterial and portal pedicles and the appropriate hepatic vein was achieved before resection. Liver transection was performed using Kelly artery forceps and an ultrasonic dissector; haemostasis was secured by sutures and clips. Biological glue was applied to the liver resection margin. No biliary drainage was used. Closed abdominal drainage was established by means of a suction drain. In all patients prophylactic antibiotics (cefotaxime 3 g per 24 h ) were given for 48 h intravenously.

~-

Duration of operation and of portal triad clamping were recorded. Resected specimens were weighed. Blood tests including haemoglobin level, white cell count, platelet count, prothrombin time, factor V level, factor 11 level, fibrinogen level, and liver function tests (including aminotransferase, 7-glutamyl transpeptidase, alkaline phosphatase and bilirubin level) were carried out before operation and after operation at days 1 , 3 and 7. All patients were examined I and 3 months after resection; examination included biological tests and liver ultrasonography. Results are presented as mean values with standard deviation. Correlations between all of the parameters with the weight of resected specimen and with the duration of vascular clamping were studied using Spearman’s rank test. Statistical analysis was performed by x2 test.

Results Operation Resection types included local excision (five ), unisegmentectomy (ten ), bisegmentectomy (nine), trisegmentectomy (one) and quadrisegmentectomy (right hepatectomy (eight ). The mean( s.d. ) weight of resected specimen was 383( 339) g (range 50- 1400 g). Patients were classified according to the weight of resected specimen into three groups: group I , < 100 g ( n = 12); group 11, 100-5OOg ( n = 1 2 ) ; and group 111, >5OOg ( n = 9 ) . Group I included all local excisions and seven unisegmentectomies ; group 11 included three unisegmentectomies and all bisegmentectomies ; group 111 included the trisegmentectomy and the eight right hepatectomies. The duration of pedicle inflow occlusion ranged from 10 to 45 min, mean(s.d.) 22( 11 ) min. The mean(s.d.) operating time was 196(54)min, range 60-340 min.

Blood test climnges utter operation Results are listed in Table 1. The maximal fall in haemoglobin level occurred on day 1 and persisted until day 7. The white cell count doubled from its preoperative level but returned to normal by day 7. A fall in platelet count was observed on day 1 and return to normal was achieved at day 7 . Maximal fall in prothrombin time, factor V and factor I1 levels occurred on day I ; prothrombin time and factor V began to rise again at day 3 and tended to return to preoperative levels by day 7 , but factor I1 remained low up to day 7. The fibrinogen level rose

~

~ 0 7 - l 3 2 3 ~ 9 ~ 0 l 0 004 3 9 (01992 Butterworth-Heinemann Ltd

39

'Natural history' of hepatectomy: B. SUC et al.

Table I

Biochemical changes after hepatectoniy in 33 non-transfused patients

After operation (days)

Haemoglobin (g/dl) White cell count (cells/mm3) Platelet count ( x lo3/mm3) AST (units/])* ALT (units/l)* 7-Glutamyl transpeptidase (units/l)* Alkaline phosphatase (units/l)t Bilirubin (pmol/l)$ Prothrombin time (TO) Factor V ( % ) Factor I1 ( % ) Fibrinogen (g/l)

Before operation

1

3

7

13.4(1.1 ) 6566(1620) 29 1(64)

12.2(1.5) 126 19(3219) 254(62) 280( 162) 420(256) 47(47) 71(31) 22.2(14) 63(16) 63(18)

1 l.7(1.7) 105333036) 256(72) 108(91) 270(206 ) 63(52) 87(36) 23.q20) 69(17) 78(33) 71(30) 4.6(5.5)

I1.4(1.3) 8229(2274) 303( 109) 63(57) 161( 142) 117(1 1 1 ) 133(93) l7.6(21 ) 75(13) 79(20) 69(20) 5.8( 1.7)

20(4) 20( 10) 61(59) 73(35) 8.9(4) 87(9) 94(13) 99(11) 3,710.9)

68(15)

3.9( 1.3)

Values are mean(s.d.). AST, aspartate aminotransferase: ALT. alanine aminotransferase. Normal ranges : $ < 15 pmol/l

* 10-40

units/l ; t25-130 units/] ;

.

Table 2 Haemoglobin, platelet count, bilirubin serum levels und prothrombin time at day I according to the weight of resected specimen after heputectomy in 33 non-transfused patients

.

Weight of resected specimen (9) Group I

Haemoglobin (g/dl)* Platelet count ( x

500

13.1 ( 1.6) 285(76)

10.8( 1 . I ) 257(59)

12.9(1.3 ) 212(39)

1o3/mm3)t

Bilirubin (pmol/l)$ Prothrombin time YO)^

12.75(4.3) 79.2(7.1) ~

15.8(7.9) 36.5(13) 64.3(11,1) 49.4(6.7) ~

Values are .nean(s.d.). *Not significant; t r , = -0.49; $ r s = 062; &rs = -0.79 (correlations with weight of resected specimen, Spearman's rank test )

2oov '

0

progressively after operation up to day 7, but returned to the preoperative level by 1 month. There was a marked rise in aminotransferase levels at day 1, with aspartate aminotransferase (AST) 14 times and alanine aminotransferase (ALT) 21 times the level before operation. At day 7 AST and ALT were respectively three and eight times their preoperative levels. For both y-glutamyl transpeptidase and alkaline phosphatase, a moderate fall in day 1 level was followed by an increased level at day 7, which persisted for 8- 12 weeks after resection. Serum bilirubin level rose up to day 3 but tended to return to normal by day I . Blood test changes and nature of operation Postoperative changes at day 1 are listed in Table 2 according to weight of resected specimen. The lowest mean haemoglobin level was observed in group 11; however, no significant correlation was observed between mean haemoglobin level and weight of the resected specimen. The lowest platelet count was observed in group 111, with an inverse correlation between platelet count and weight of resected specimen (rs = -0.49). The highest bilirubin level was observed in group 111, with a significant correlation between bilirubin level and weight of resected specimen ( r s = 0.62). The lowest prothrombin time was observed in group 111, with a significant inverse correlation between prothrombin time and weight of resected specimen ( r s = -0.79). A significant correlation was observed between y-glutamyl transpeptidase at day 3 and weight of resected specimen ( r s = 0.78). Fibrinogen level at day 7 was inversely correlated with the weight of resected specimen (rs = -0.67).

40

/

(n=9)

10

20

30

40

50

Duration of pedicle inflow occlusion (min) Figure 1 Relationship between alunine uminotrunsferase ( A L T ) level ot day I und duration qfprdicle inflow occlusion after hepatectomy in 33 non-trmwfused patients ( rs = 0.49; P < 0.05)

No significant correlation was observed between the weight of resected specimen and aminotransferase or alkaline phosphatase levels. The duration of pedicle inflow occlusion showed a correlation ( r s = 0.49) with day 1 levels of both AST and (Figure 1 ) ALT.

Discussion During the last decade, despite progress in the surgical technique of liver resection leading to a lower mortality rate, postoperative complications have remained a significant p r ~ b l e m ~The . ~ .period after operation may be complicated by bleeding, infection and liver f a i l ~ r e ~A ,complete ~ ~ ~ . assessment using biochemical tests is required for early recognition of these complications. Many studies have tried to evaluate the postoperative biochemical changes in patients after hepatect ~ m y ' ~ - but ' ~ ,the results of these studies are difficult to analyse because of the inclusion of patients with transfusion, underlying liver disease and in some cases patients with postoperative complications. All these situations are known to modify biochemical tests after In patients with problems such as biliary complications and

Br. J. Surg., Vol. 79, No. 1, January 1992

'Natural history' of hepatectomy: 6.SUC et al.

intra-abdominal sepsis, several biochemical changes can be observed, including prolonged leucocytosis, thrombocytopenia and a rise in aminotransferase and alkaline phosphatase serum levels3,5.1 1 . 1 5 . 1 6 . persistent decrease in prothrombin time has been observed in postoperative liver failure4. In patients with underlying liver disease, the assessment of postoperative biochemical tests is difficult for two reasons : preoperative blood tests are frequently impaired and liver regeneration after hepatectomy can be In transfused patients, many disturbances of biochemical and haematological tests have been described : fall in platelet count, decrease in fibrinogen level and postoperative elevation of aminotransferase and bilirubin levelsl.6.9.11.15 Minimizing blood loss is a prime concern of the liver surgeon and the avoidance of blood and plasma transfusion is advisable for a number of reasons including transmission of viral d i s e a ~ e ' ~the , ~ close ~ , correlation between operative blood loss and postoperative complications' 5 * z 1 , z z and the apparent association between transfusion and increased risk of recurrence of malignant tumoursz3.Vascular clamping is the most effective method of undertaking hepatic resection with minimal blood 10ssz43z5.The pedicle inflow occlusion induces liver ischaemia and subsequently changes in aminotransferase serum levelsz4. The present results confirm that the rise in transaminases is greatest between days 1 and 2 and that a decrease to normal levels is achieved between days 7 and 10 when no complication occurs1*5-15. The amount of liver resected has been implicated in the rise of transaminases after hepatectomy'0~'5~zz , but no correlation between the extent of resection and aminotransferase levels was found in the present series. On the other hand, a correlation between duration of vascular clamping and aminotransferase level was confirmedz6. The decrease in haemoglobin level is greatest at day 1, reflecting blood loss. It has been reported that blood loss is significantly higher in major resection than in minor or non-anatomical r e s e ~ t i o n ~ .~Present ~ ' - ~ ~ data do not confirm this relationship. Minimizing operative blood loss is best achieved by avoiding difficult non-anatomical resection where vascular control is less easy. The only data published regarding posthepatectomy leucocytosis are of an experimental study in which a rise in white cells, prolonged over several weeks, is described3'. Present results suggest that a white cell count above 10000/mm3at the end of the first week is abnormal and may be related to developing complications. The immediate fall in platelet count after hepatectomy has been ascribed to t r a n s f u s i ~ n ~The ~ ~ ~absence ' ~ . of transfusion and the correlation between fall in platelet count at day 1 and extent of resection observed in our patients suggest that this is also due to liver resection. After hepatectomy, a decrease in prothrombin time and level of factor V followed by rapid return to normal levels with 7-10 days has been r e p ~ r t e d ' ~Transfusion . and the amount of parenchyma resected have both been i m p l i ~ a t e d ~ . The ~.~~. absence of transfusion and the significant inverse correlation between prothrombin time and weight of resected specimen in the present data suggest that prothrombin time is a sensitive indicator of postoperative liver function. Both factor V and factor I1 have been considered as useful indicators of postoperative liver functionz6. We confirm that restoration of factor V is achieved by the end of the first week, but factor I1 returns to normal later in the postoperative period. After hepatectomy, normal or decreased fibrinogen levels have been described' Decreased levels were often related to multiple transfusions" although in the present series a progressive rise during the first week was observed and fibrinogen level at day 7 was inversely correlated with the extent of resection. In those patients without complications the rise in fibrinogen level may reflect hepatic regeneration. The rise in both alkaline phosphatase and y-glutamyl transferase after hepatectomy has been reported in clinical and experimental studies1'.I6. Both were considered as indicators

Br. J. Surg., Vol. 79, No. 1, January 1992

of hepatic regeneration3'. In the present study, without biliary complications, it was confirmed that persistent elevation of alkaline phosphatase and y-glutamyl transferase is not pathological until 3 months after operation and may also reflect hepatic regeneration. In several studies, the increase in bilirubin level after hepatectomy has been attributed to transfusion, underlying liver disease, biliary complications and to the amount of parenchyma 1,17,zz.The present study demonstrates that the rise in bilirubin level after hepatectomy correlates significantly with the amount of liver resected. It appears to be a highly sensitive indicator of liver function. The most important finding of this study is that transient common biochemical changes are observed after uncomplicated hepatectomy. Those biochemical changes are related either to the extent of resection or to the duration of operative liver ischaemia. The absence of underlying liver disease and of perioperative blood and plasma transfusion in this selected group of patients allows a description of the 'natural history' of hepatectomy. The knowledge of these 'natural' changes may contribute to early detection ofcomplications after operation.

References I. 2. 3. 4. 5. 6. 7.

8. 9. 10. 11.

12.

Franco D, SmadjaC, Meakins JL, Wu A, Berthoux L, Grange D. Improved early results of elective hepatic resection for liver tumors. Arch Surg 1989; 124: 1033-7. Ryan WH, Hummel BW, McClelland M . Reduction in the morbidity and mortality of major hepatic resection. A m J Surq 1982; 144: 740-3. Pace RF, Blenkharn JI, Edwards WJ, Orloff M, Blumgdrt LH, Bejamin IS. lntraabdominal sepsis after hepatic resection. Ann Surg 1989; 209: 302-6. Bismuth H, Houssin D, Mazmanian G . Postoperative liver insufficiency: prevention and management. World J Surg 1983; 7 : 505-10. Stone M, Benotti P. Liver resection: preoperative and postoperative care. Surg CIin North A m 1989; 69: 383-91. Zuker MB, Siege1 M, Cliffton EE, Bellville JW, Howland WS. The effect of hepatic lobectomy on some blood clotting factors and on fibrinolysis. Ann Surg 1957; 146: 772-81. Makuuchi M, Takayama T, Gunven P, Kosuge T, Yamasaki S, Hasegawa H. Restrictive versus liberal blood transfusion policy for hepatectomies in cirrhotic patients. World J Surg 1989 ; 13: 644-8. Stimpson REJ, Pellegrini CA, Way LW. Factors affecting the morbidity of elective liver resection. Am J Surg 1987; 153: 189-97. Thompson H, Tompkins RK, Longmire WP. Major hepatic resection. Ann Surg 1983; 197: 175-88. Almersjo 0, Bengmark S, Hafstrom LO, Olsson R. Enzyme and function changes after extensive liver resection in man. Ann Surg 1969; 169: 111-19. Aronsen KF, Ericsson B, Pihl B. Metabolic changes following major hepatic resection. Ann Surg 1969; 169: 102-10. Mann FD, Shonyo ES, Mann FC. Effect of removal of the liver on blood coagulation. Ann Surg 1950; 164 : 11 1 16. Pinkerton JA, Sawyers JL, Foster J H . A study of the postoperative course after hepatic lobectomy. Ann Surg 1971 ; 173: 800-9. Zoli M, Marchesini G, Melli A, Viti G, Marra A, Pisi E. Evaluation of liver function following hepatic resection in man. Liver 1986; 6: 286-91. Ekberg H, Tranberg KG, Anderson R, Jeppson B, Bengmark S Major liver resection : perioperative course and management. Surgery 1986; 100: 1-7. Burke J. Serum alkaline phosphatase in liver disease. A concept of significance. Gastroenterology 1950 ; 16 : 660-2. Nagasue N, Yukaya H, Ogawa Y, Kohno H, Nakamura T. Human liver regeneration after major hepatic resection. Ann Surg 1987; 206: 30-9. Chen M , Hwang T , Hung C. Human liver regeneration after major hepatectomy. Ann Surg 1991 ; 213: 227-9. Alter HJ, Prucell RH, Shih JW et al. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med 1989; 231: 1494-500. -

13. 14. 15. 16. 17. 18. 19.

41

'Natural history' of hepatectomy: B. SUCet al. 20.

21.

22. 23.

24. 25.

42

Menitove JE. Current risk of transfusion-associated human immunodeficiency virus infection. Arch Pathol L a b Med 1990 ; 114 330-4. Coppa G F , Eng K, Ranson JHC, Gouge T H , Localio SA. Hepatic resection for metastatic colon and rectal cancer. Ann Surg 1985; 202: 203-8. Makuuchi M, Mori T, Gunven P, Yamasaki S, Hasegawa H. Safety of hemihepatic vascular occlusion during resection of the liver. Surg Gynecol Obstet 1987; 164: 155-8. Stephenson KR, Steinberg SM, Hughes KS, Vetto JT, Sugarbaker PH, Chang AE. Perioperative blood transfusions are associated with decreased time to recurrence and decreased survival after resection of colorectal liver metastases. Ann Suvg 1988; 208: 679-87. Delva E, Camus Y, Nordlinger B et al. Vascular occlusions for liver resections. Operative management and tolerance to hepatic ischemia: 142 cases. Ann Surg 1989; 209: 211-18. Terblanche J, Krige JE, Bornman PC. Simplified hepatic

resection with the use of prolonged vascular inflow occlusion. Arch Surg 1991 ; 126: 298-301.

26. 27. 28. 29.

30. 31.

Ryan JA, Faulkner DJ. Liver resection without blood transfusion. Am J Surg 1989; 157: 472-5. Bismuth H, Castaing D , Garden OJ. Major hepatic resection under total vascular exclusion. Ann Surg 1989; 210: 13-19. Nagao T, Inoue S, Mizuta T, Saito H, Kawano N , Morioka Y. One hundred hepatic resections. Ann Surg 1985; 202: 42-9. Brown DA, Pommier RF, Woltering EA, Fletcher WS. Non anatomic hepatic resection for secondary hepatic tumors with special reference to hemostatic technique. Arch Surg 1988; 123: 1063-6. RO JS, Flatmark A. Haemostatic studies following extensive liver resection in dogs. Scund J Gastroenterol 1973; 8 : 615-20. Sulakhe SJ. The activity of gamma glutamyl-transpeptidase in regenerating rat liver. FEBS Lett 1986; 204: 302-6.

Paper accepted 12 September 1991

Br. J. Surg., Vol. 79, No. 1, January 1992

'Natural history' of hepatectomy.

The aim of this study was to describe biochemical and liver function test changes after hepatectomy in 33 patients with the following characteristics:...
416KB Sizes 0 Downloads 0 Views