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Hepatic resections in normothermic ischemia
Hepatic resections in normothermic ischemia Gennaro Nuzzo, MD, Felice Giuliante, MD, Ivo Giovannini, MD, Giovanni D. Tebala, MD, and Germano de Cosmo, MD, Rome, Italy
Background. Reduction of operative blood transfusions is a primary goal in resective surgery of the liver. Tempormy vascular inflow occlusion is an effective method to decrease hemorrhage during hepatic resection. This study was performed to assess the impact of normothermic ischemia on intraoperative bleeding and outcome after hepatic resection. Methods. Sixty-one hepatic resections were performed by using pedicle clamping alone or associated with total vascular exclusion of the livet: The mean duration of normothermic isehemia was 40 +- 18 minutes O'ange, 7 to 98 minutes). Major resections were performed in 32 cases (52.5 %). Results. Operative mortality was nil. Major complications occurred in 11.5 % of cases. Twenty-five patients (41%) received intraoperative blood transfusions; mean +_ SD of transfused blood units was 2.4 + 1.3. Twelve major resections (3Z5 %) did not require any transfusion. Postoperative changes in liver function test results wei'e moderate and transient. Conclusions. The results of this study confirm the benefit of vascular occlusion techniques in reducing" intraoperative bleeding and postoperative complications. The routine use of these techniques during hepatic resections, if applied properly and with the necessary precautions, is not associated with severe adverse effects on liver function. (Surgery 1996;120:852-8.) From the Departments of Gedat,ic Surgery and of Anesthesiology, Catholic UniversityMedical School, Rome, Italy
OPERATIVE MORTALITYAND MORBIDITYofhepatic resection
have b e e n significantly r e d u c e d in r e c e n t years; however, bleeding remains the most i m p o r t a n t intraoperatire risk factor. T h e demonstration of a g o o d tolerance of the liver to n o r m o t h e r m i c ischemia, even for prolonged periods o f time, 1-5 has p e r m i t t e d the use of various techniques of hepatic ischemia to reduce the entity of intraoperative h e m o r r h a g e and to e n h a n c e the resectability rate of neoplastic lesions, z' 6-17 It has b e e n shown that hepatic pedicle clamping (HPC) is a safe technique to control bleeding from intraparenchymal portal mad arterial pedicle branches.5, 9, 16, 18, 19 This m a n e u v e r has been used generally in emergency, and at present it is also applied as a routine maneuver during liver resection and also in cirrhotic liver.24, 9, zo, 21 However, the routine use of HPC is n o t widely accepted because of the fear of adverse hemodynamic effects a n d o f i s c h e m i c damage to the liver, particularly in patients with liver cirrhosis or with o t h e r causes o f i m p a i r m e n t o f hepatic function. 12 Total vascular exclusion (TVE) of the liver is necessary to Accepted for publication April 4, 1996. Reprint requests: Gennaro Nuzzo, MD, Cattedra di Chirurgia Geriatrica, Universit~ Cattolica del S. Cuore, L.go Agostino Gemelli, 8 - 00168 Roma, Italy. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00 + 0 852
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control suprahepatic caval bleeding, which is the most i m p o r t a n t cause o f concern during hepatic resection, a n d to resect lesions close to the vena cava o r to the suprahepatic caval confluence. 5-7' 17 The aim o f this study was to evaluate the influence of hepatic ischemia obtained by routine use of HPC, alone or associated with caval clamping (TVE), on postoperative o u t c o m e in 61 patients who u n d e r w e n t hepatic resection.
METHODS Between April 1989 and May 1995, 61 liver resections were p e r f o r m e d u n d e r hepatic n o r m o t h e r m i c ischemia. T h e 27 m e n a n d 32 women (two female patients u n d e r w e n t reresection) h a d a m e a n age o f 56 - 15 years (range, 2 to 76 years). In 47 cases (77%) the indications for liver resection were malignant tumors; the m o r e frequent ones were metastases from colorectal cancer (24 cases). Liver cirrhosis (Child-Pugh class A) was present in 9 patients; 14 patients h a d u n d e r g o n e preoperative systemic chemotherapy. In 14 cases (23%) liver resection was perf o r m e d for benign liver disease. In Table I the indications for hepatic resection are listed in detail. A major liver resection (that is, a resection o f at least three segments) was p e r f o r m e d in 32 cases (52.5%). As defined by C o u i n a u d ' s liver anatomy, zz 3 right e x t e n d e d hepatectomies, 1 left e x t e n d e d hepatectomy, 11 right hepatectomies, 6 left hepatectomies, 10 resections o f
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T a b l e I. Indications for hepatic resection in 61 cases Malignant tumors Metastases From colorectal cancer From noncolorectal cancer Hepatocellular carcinoma Gallbladder carcinoma Hepatoblastoma Cholangiocarcinoma Hilar carcinoma Benign diseases Focal nodular hyperplasia Hydatid cyst Hemangioma Cysts Intrahepatic lithiasis Adenoma Abscess
47 (77%) 30 24 6 9 3 2 2 1 14 (23%) 4 3 2 2 1 1 1
three segments, a n d 1 resection o f four segments (III, IV, V, a n d VI) were p e r f o r m e d (Table II). In two cases a tangential resection o f the retrohepatic vena cava, with TVE, was associated with right hepatectomy. In 29 cases (47.5%) a m i n o r liver resection was performed. All patients were o p e r a t e d on electively and by the same surgeon (G.N.). Surgical exposure was always t h r o u g h a bilateral subcostal laparotomy enlarged with a sternal split. Parenchymal transection was d o n e by Kelly clamps, and hemobiliostasis was obtained by use o f transfixed sutures of thin reabsorbable material, according to the technique described by Bismuth. 23"25HPC was p e r f o r m e d systematically with a vascular tourniquet. Attention was paid to apply the tourniquet at a safe distance from the pancreas. In the presence o f a left hepatic artery coming from the gastric artery t h r o u g h the gastrohepatic ligament, such artery was also clamped. To reduce clamping time, the maneuver was started after the section of Glissonian's capsule and o f the superficial parenchymal layers. After completion o f the resection, inflow occlusion was released and any residual b l o o d or bile leaks were sutured. In eight cases TVE o f the liver was used (Table III). This r e q u i r e d careful isolation of the inferior vena cava, from the d i a p h r a g m to the renal veins. After the pedicle was c l a m p e d with a tourniquet, tile cava was closed below the liver with a De Bakey clamp (placed above the confluence with the right adrenal vein; alternatively this vein was divided and suture ligated). T h e n the cava was closed above the liver with a Satinsky clamp. In two o f these patients h e m o d y n a m i c tolerance to this technique was initially poor. In o n e patient the maneuver was tolerated after consistent b l o o d volume expansion with clTstalloids; in the o t h e r patient vascular exclusion
853
T a b l e II. Type o f resection in 61 cases Major resections Right hepatectomy Extended right hepatectomy (to segment IV) Left hepatectomy Extended left hepatectomy (to segments V and VIII) Resection of 3 segments Resection of 4 segments Minor resections Resection of 2 segments Resection of 1 segment Atypical resection
32 (52.5%) 11" 3 6 1 10 1 29 (47.5%) 18 9 2
* T a n g e n t i a l r e s e c t i o n o f r e t r o h e p a t i c v e n a cava i n 2 cases.
n e e d e d to be discontinued a n d the resection was p e r f o r m e d with pedicle clamping only. This corres p o n d e d to an intolerance rate to TVE o f 12%. Neither topical refrigeration n o r hypothermic liver perfusion was used. T h e average duration o f n o r m o t h e r m i c hepatic ischemia was 40 • 18 minutes (range, 7 to 98 minutes); in 13 patients (21%) ischemia was p r o l o n g e d for 60 minutes or more. In some instances, in patients older than 70 years of age, in patients with liver cirrhosis or jaundice, or in patients who previously u n d e r w e n t systemic chemotherapy, HPC was discontinued for 5 minutes every 10 to 15 minutes o f i s c h e m i a (10 patients). In one patient who u n d e r w e n t right hepatectomy with tangential caval resection, the surgeon d e c i d e d to proceed to caval resection after 45 minutes o f HPC. HPC was i n t e r r u p t e d for 10 minutes (impaired liver function from previous c h e m o t h e r a p y was also a cause o f concern in this patient), a n d then a TVE was p e r f o r m e d for 53 minutes. T h e total time o f liver ischemia was 98 minutes. At the e n d of the p r o c e d u r e o n e or two silicon drains were positioned in all patients. T h e mean d u r a t i o n o f the p r o c e d u r e was 291 • 108 minutes. Prophylaxis or postoperative treatment with anticoagulants was n o t used in any patient. To verify the influence of warm liver ischemia on postoperative course, the following factors was evaluated: perioperative mortality and morbidity rates, numb e r of patients who r e q u i r e d intraoperative b l o o d transfusions, n u m b e r of units transfused, time r e q u i r e d for operation, postoperative profiles of levels o f aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, p r o t h r o m b i n time, a n d total cholesterol, a n d postoperative stay. Results are r e p o r t e d as m e a n -+ SD. Comparisons were det e r m i n e d by using Student's t test; a p value below 0.05 was considered significant.
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T a b l e III. Features of patients who underwent TVE
Age (yr)
Disease
57
Colorectal cancer metastasis
58 39
Cholangiocarcinoma Retroperitoneal leiomyosarcoma metastases Colorectal cancer metastases Breast cancer metastases Anal cancer metastasis Colorectal cancer metastases
73 33 61 59
45
Colorectal cancer metastases
Resection
Ischemia time (rain)
TVE time (rain)
Complications
Right hepatectomy + tangential caval resection Right hepatectomy Bisegmentectomy
75
40
Pleural effusion (with thoracentesis)
54 42
23 35
Moderate liver failure --
Left hepatectomy
50
NT*
Left hepatectomy + atypical resections Extended left hepatectomy Right hepatectomy + tangential caval resection
60
5
80
20
98
53
52
7
Right hepatectomy
Severe liver failure, subphrenic abscess, pleural effusion (with thoracentesis)
*NT, N o t tolerated.
T a b l e IV. Morbidity in 61 hepatic resections (overall morbidity of 12 cases [19.7%])
Type of complication Major (7 cases* [11.5%]) Severe liver failure Biliary fistula Subphrenic abscess Minor (5 cases* [8.2%]) Moderate liver failure Pneumonia Pleural effusion (with thoracentesis)
3 3 3 2 3 2
*3 cases with m o r e than one complication.
RESULTS
Overall operative mortality in this group of patients was nil. Postoperative complications were observed in 12 cases (19.7%), none of which required a reoperation. Major complications occurred in seven cases (11.5%) and minor complications occurred in five cases (8.2%) (Table IV). Five patients experienced postoperative liver failure. Two of them (including a 73-year-old patient with cirrhosis) had only postoperative ascites and total bilirubin elevation below 3 m g / d l (moderate liver failure). The other three patients experienced severe liver failure (encephalopathy, persistent jaundice, ascites); all of them had undergone resection for malignant disease with a duration of hepatic ischemia of 40, 68, and 98 minutes, respectively. A major liver resection was per-
tormed in two of them; in one case, subphrenic abscess and pleural effusion, treated with thoracentesis, were also associated. A minor resection was performed in the third patient, who had metastases from retroperitoneal leiomyosarcoma; this patient, who had already undergone resection 16 months before and had received subsequently multiple cycles of systemic chemotherapy, also had a subphrenic abscess. Pleural effusion occurred in 15 cases (25 %), but it was considered to be a complication only when a thoracentesis was required (2 patients). In patients in w h o m TVE was used, total morbidity rate was 37.5%, but major complications developed only in one patient (12.5%) (Table III). Postoperative morbidity rate in 13 cases with liver ischemia lasting more than 1 hour (30.8%) was not significantly higher compared with the remainder with liver ischemia lasting less than 1 hour (16.7%). In the former group 12 patients (92%) had undergone a major resection. Age older than 65 years, presence of cirrhosis, preoperative systemic chemotherapy, extent of hepatic resection, and ischemia longer than 1 hour were not associated with significantly higher morbidity rates (Table V). Twenty-five (41%) patients received intraoperative blood transfusions (Table VI) In these the average of transfused blood units was 2.4 + 1.3 units (range, 1 to 6 units); however, six of these patients received only 1 blood unit. Twelve major resections (37.5%) were performed without any blood transfusion. Three patients (43%) who underwent hepatic resection with TVE did not receive any blood transfusion.
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T a b l e V. Morbidity in relation to specific factors Complicated cases Total
n
%
Overall morbidity 61 Age (yr) >65 17 <65 44 Cirrhosis Yes 9 No 52 Preoperative chemotherapy Yes 14 No 47 Resection Major 32 Minor 29 Ischemia (hr) >1 13 <1 48
12
19.7
2 10
11.8 22.7
1 11
11.1 21.2
3 9
21.4 19.1
8 4
25.0 13.8
4 8
30.8 16.7
A significant increase ofAST, ALT (ALT > AST), total bilirubin, and conjugated bilirubin a n d a significant fall of p r o t h r o m b i n time a n d total cholesterol, comp a r e d with preoperative values, were n o t e d on postoperative day 1; in most instances values t e n d e d to r e t u r n to n o r m a l ranges within 1 week, except for ALT values (Table VII). Patients with an hepatic ischemia of 60 minutes o r m o r e h a d wider alterations of biochemical values with respect to patients with a less p r o l o n g e d ischemia, b u t the general t r e n d toward the n o r m a l values was similar (Table VIII). The patients in whom severe postoperative liver thilure developed had significantly greater hematochemical abnormalities on postoperative day 1 c o m p a r e d w i t h the variations observed in the remainder. Moreover, in this g r o u p the trend o f the hematochemical values to return toward n o r m a l ranges was significantly delayed; bilirubin a n d total cholesterol were the latest values to r e t u r n to n o r m a l ranges (Table IX). Overall m e a n postoperative stay was 18 -+ 14 days. DISCUSSION T h e reduction of operative blood loss and, consequently, o f the n u m b e r o f transfusions is considered a primary goal in resective surgery of the live r ) ' 2, 6, 13, 18, 21, 26-28 It has been shown that, independ e n t of the risk of transmission of viral diseases and o f i m m u n e reactions, operative mortality and morbidity rates are affected by the n u m b e r of b l o o d transfusions. 2s F u r t h e r m o r e , several authors have emphasized that the long-term results of surgery for neoplastic diseases are m o r e satisfactory in patients who did n o t receive b l o o d transfusions. 29-32 This last issue is of particular interest
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T a b l e VI. Intraoperative b l o o d transfusions in 61 cases n
Total Resection Major Minor TVE Yes No
Transfused cases n (%)
Units of blood (range)
61
25 (41)
2.4 - 1.3 (1-6)
32 29
20 (62.5) 5 (17.2)
2.5 -+ 1.4 (1-6) 2.0 -+ 0.6 (1-3)
7* 54
4 (57) 21 (38.9)
3.7 - 1.5 (2-6) 2.1 -+ 1.0 (1-5)
*One patient did not tolerate TVE and was excluded.
if one considers that malignant tumors are the m o r e c o m m o n indication for liver resection; in o u r series malignancies r e p r e s e n t e d 77.1% of the indications for surgery. T e m p o r a r y vascular inflow occlusion of the liver represents an easy technique to reduce the risk o f b l e e d i n g d u r i n g hepatic resections. Even if the efficacy a n d the safety of the pedicle clamping, as described by Pringle 19 in 1908, for p r o l o n g e d periods o f time a n d in cirrhotic livers are already well d o c u m e n t e d , 1-5' 13, 21, 33 controversies still exist a b o u t the tolerance of the liver to warm ischemia. Since April 1989 the use of hepatic pedicle clamping (HPC) has b e e n i n c l u d e d in our r o u t i n e app r o a c h to liver resection. At the m o m e n t we consider the n e e d to p e r f o r m simultaneously a colon resection a n d the presence o f d e e p j a u n d i c e as relative contraindications to the use of this technique. In the first instance we tend to avoid pedicle clamping because of the risk of vascular p r o b l e m s a n d e d e m a to the colon anastomosis. In the case o f d e e p j a u n d i c e liver function is already severely c o m p r o m i s e d a n d the application of techniques of vascular occlusion has to be limited to emergency situations only. Clamping o f the cava below a n d above the liver associated with HPC allows TVE o f the liver and also permits control of h e m o r r h a g e from hepatic veins or from the inferior vena cava. With the use o f TVE it is possible to p e r f o r m hepatic resections in patients with large or posterior tumors, r e d u c i n g the risk of bleeding. This technique is well tolerated in most patients. < 6, 34 In our experience interruption o f TVE was necessary only in one case. T h e results of our analysis confirm the efficacy of techniques o f vascular occlusions such as HPC a n d TVE. As a matter of fact in this series with more than 50% of major resections, almost 60% o f the p r o c e d u r e s was p e r f o r m e d without any b l o o d transfusion. In addition, in transfused patients the a m o u n t of transfused b l o o d was very limited (2.4 -+ 1.3 units [i.e., 720 -+ 390 ml]), a n d six o f these patients received only 1 b l o o d unit. Use o f these m e t h o d s o f vascular occlusion reduces
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T a b l e V I I . Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s o n 58 p a t i e n t s *
Preoperative AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) P r o t h r o m b i n time (%)
31.0 42.5 0.7 0.3 189.8 93.5
• 25.1 • 64.0 _+ 0.7 -+ 0.4 • 37.7 • 12.4
Day 1 409.4 468.1 1.8 0.6 117.2 58.7
~+ 345.5 _+ 365.0 + 1.3 + 0.5 + 29.9 + 19.3
Day 3 86.0 241.2 1.3 0.5 125.5 75.1
+ 97.7 -+ 232.3 -+ 1.0 + 0.7 + 34.6 +_ 18.6
Day 7 41.2 118.0 1.3 0.7 125.4 80.5
• 24.9 • 88.3 _+ 1.5 • 1.3 • 47.0 • 15.1
Values are nrean _+ SD. Day 1 versus p r e o p e r a t i v e values, p < 0,05. *Patients with severe postoperative liver failure were e x c l u d e d f r o m this evaluation.
T a b l e V I I I , Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s i n r e l a t i o n to liver i s c h e m i a t i m e
Preoperative
Day 1
Day 3
Day 7
i
<1 h r AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%) >1 h r AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%)
33.0 46.6 0.8 0.3 188.2 92.9
• • • + • +
27.0 69.8 0.8 0.5 35.9 12.2
358.8 421.4 1.7 0.5 116.2 60.0
_+ 278.3 _+ 308.6 _+ 1.4 _+ 0.5 _+ 30.1 _+ 20.0
66.9 202.9 1.2 0.5 129.7 76.4
_+ 50.4 -+ 187.5 -+ 0.9 • 0.5 -+ 34.3 -+ 18.5
36.7 110.1 1.1 0.4 126.3 82.2
_+ 15.0 +_ 83.4 _+ 0.9 +- 0.5 _+ 51.1 -+ 14.1
22.6 25.4 0.6 0.1 197.1 96.2
• 11.9 • 21.5 -+ 0.2 • 0.1 -+ 44.6 -+ 13.2
616.4 658.9 1.9 0.9 121.4 54.5
_+ 487.4 _+ 493.5 _+ 0.8 • 0.7 _+ 28.7 _+ 16.3
162.4 394.4 1.6 0.9 111.0 70.8
• 173.8 -+ 315.8 • 1.4 • 1.1 + 31.6 • 18.2
54.6 140.7 1.9 1.4 123.1 78.0
• + + + • +
39.4 97.5 2.6 2.3 35.4 16.0
Values are m e a n • SD. Day 1 versus preoperative values, p < 0.05. Patients who h a d severe postoperative liver failure were e x c l u d e d from this evaluation.
T a b l e I X . Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s i n 3 p a t i e n t s w i t h severe p o s t o p e r a t i v e liver failure
Preoperative AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%)
22.3 20.33 0.5 0.1 167.0 93.7
-+ 0.9 _+ 3.1 -+ 0.2 _+ 0.1 _+ 32.3 _+ 12.5
Day 1 1593.3 • 1476.7 + 3.7 • 1.7.• 88.3 • 36.7 +
809.0 1116.1 1.3 0.2 28.6 8.7
Day 3 312.7 704.3 5.8 3.1 81.3 45.8
• 136.1 • 522.6 + 2.4 • 1.2 +- 35.5 _+ 8.6
Day 7 67.33 199.7 8.2 5.3 96.0 69.0
_+ 26.7 + 107.7 • 4.5 • 3.1 • 28.1 • 9.9
Vahles are m e a n _+ SD.
p o s t o p e r a t i v e m o r b i d i t y r a t e also by allowing a m o r e acc u r a t e surgical t e c h n i q u e . I n fact, w i t h inflow v a s c u l a r o c c l u s i o n it is p o s s i b l e to w o r k i n a b l o o d l e s s o p e r a t i v e field a n d t h e r e f o r e a m o r e a c c u r a t e h e m o s t a s i s a n d b i b iostasis c a n b e p e r f o r m e d , I n this series overall m o r b i d ity r a t e was less t h a n 2 0 % a n d m a j o r c o m p l i c a t i o n s w e r e o b s e r v e d i n only s e v e n p a t i e n t s ( 1 1 . 5 % ) ; n o n e o f t h e s e required a reoperation. Liver failure is a p o s t o p e r a t i v e c o m p l i c a t i o n specifically r e l a t e d to h e p a t i c r e s e c t i o n . 35 T h e o c c u r r e n c e o f this c o m p l i c a t i o n is r e l a t e d to t h e a m o u n t a n d to t h e
f u n c t i o n a l a d e q u a c y o f tile r e s i d u a l liver p a r e n c h y m a ; cirrhosis is t h e c o n d i t i o n m o r e a t risk. I n this s t u d y we obseiwed severe p o s t o p e r a t i v e liver failure i n t h r e e patients. I n all o f t h e m t h e d u r a t i o n o f i s c h e m i a was l o n g e r t h a n 40 m i n u t e s . F o r two o f t h e m s o m e p r e o p e r a t i v e i m p a i r m e n t o f liver f u n c t i o n c o u l d b e i m p l i c a t e d bec a u s e o f p r o l o n g e d systemic c h e m o t h e r a p y ; o n e p a t i e n t u n d e r w e n t r i g h t h e p a t e c t o m y w i t h v e n a cava r e s e c t i o n , a n d t h e o t h e r o n e u n d e r w e n t r e r e s e c t i o n o f two segments. The third patient underwent right hepatectomy e x t e n d e d to s e g m e n t IV a n d r i g h t a d r e n a l e c t o m y .
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T h e s e o b s e r v a t i o n s c o n f i r m t h a t t h e risk o f p o s t o p e r a tive liver f a i l u r e is e n h a n c e d , as a l r e a d y r e p o r t e d by o t h e r a u t h o r s , 4 by t h e c o m b i n a t i o n o f p o s t c h e m o t h e r apy h e p a t i c d a m a g e , p r o l o n g e d liver i s c h e m i a , a n d extensive r e s e c t i o n . I n t h e g r o u p o f p a t i e n t s w i t h c i r r h o s i s a m o d e r a t e deg r e e o f liver failure was o b s e r v e d o n l y in o n e case a f t e r r i g h t h e p a t e c t o m y f o r h e p a t o c a r c i n o m a . Also i n t h e s e p a t i e n t s t h e use o f H P C p e r m i t t e d p e r f o r m a n c e o f liver r e s e c t i o n w i t h o u t b l o o d t r a n s f u s i o n s in 4 4 % o f t h e cases, a n d in t h e t r a n s f u s e d p a t i e n t s t h e n u m b e r o f b l o o d u n i t s (2.4 + 1.5) was s i m i l a r to t h a t o f p a t i e n t s w i t h o u t cirrhosis (2.4 -+ 1.3). T h e low m o r b i d i t y r a t e o b s e r v e d in p a t i e n t s w i t h c i r r h o s i s (12.5%) was likely a result of both an accurate preoperative selection of the p a t i e n t s a n d a m e t i c u l o u s p r e p a r a t i o n f o r surgery. W i t h r e g a r d to t h e t e c h n i c a l safety o f t h e s e v a s c u l a r o c c l u s i o n t e c h n i q u e s , n o specific c o m p l i c a t i o n o f H P C o r TVE was o b s e r v e d , s u c h as i n j u r y to biliary o r vascular structures o f p o r t a l pedicle o r to inferior v e n a cava. It s h o u l d b e m e n t i o n e d t h a t particular a t t e n t i o n was p a i d to p u t t h e t o u r n i q u e t for pedicle c l a m p i n g away f r o m t h e p a n c r e a s a r o u n d t h e s u p e r i o r t h i r d o f t h e pedicle. T h e g o o d t o l e r a n c e o f t h e liver to i s c h e m i a was c o n f i r m e d in this s t u d y by a n a l y z i n g p o s t o p e r a t i v e variat i o n s o f liver f u n c t i o n test results. B i o c h e m i c a l evaluation of hepatic fnnction did not show any relevant or persistent variations in patients with ischemia lasting more than 1 hour or in patients with ischemia lasting less t h a n 1 h o u r . T h e t r e n d o f r e t u r n t o w a r d n o r m a l r a n g e s was significantly a l t e r e d o n l y i n t h e p a t i e n t s w h o h a d severe p o s t o p e r a t i v e liver failure. A n a s p e c t t h a t d e s e r v e s f u r t h e r i n v e s t i g a t i o n is t h e possibility o f r e c o g n i z i n g early i n p o s t o p e r a t i v e c o u r s e t h e p a t t e r n s t h a t a r e p r e d i c t i v e o f t h e s u b s e q u e n t d e v e l o p m e n t o f liver failu r e ; this m a y h e l p d i s c r i m i n a t e e a r l i e r t h e p a t i e n t s w i t h a greater need for careful monitoring and supportive care. I n c o n c l u s i o n , t h e results in this study c o n f i r m t h e u s e f u l n e s s o f v a s c u l a r o c c l u s i o n t e c h n i q u e s d u r i n g resective s u r g e r y o f t h e liver. T h e s e t e c h n i q u e s allow us to m i n i m i z e i n t r a o p e r a t i v e b l e e d i n g with t h e n e e d f o r b l o o d t r a n s f u s i o n s a n d allow a m o r e c a r e f u l o p e r a t i v e t e c h n i q u e w i t h a low r a t e o f p o s t o p e r a t i v e c o m p l i c a tions. I n a d d i t i o n , T V E m a y c o n t r i b u t e to i n c r e a s i n g t h e i n d i c a t i o n s f o r s u r g e r y f o r lesions at h i g h risk o f b l e e d ing. T h e results also s h o w t h a t u s e o f H P C a n d TVE, w h e n c a r r i e d o u t p r o p e r l y a n d with t h e n e c e s s a r y p r e c a u t i o n s , is n o t a g g r a v a t e d b y u n b e a r a b l e adverse effects o n liver f u n c t i o n . REFERENCES
1. Delva E, Camus Y, Paugam C, Pare R, Hnguet C, Lienhart A. Hemodynamic effects of portal triad clamping in humans. Anesth Analg 1987;66:864-8. 2. Delva E, Camus Y, Nordlinger B, et aL Vascular occlusions for
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liver resections: operative management and tolerance to hepatic ischemia--142 cases. Ann Surg 1989;209:211-8. 3. Huguet C, Gavelli A, Addario Chieco P, et al. Liver ischeinia for hepatic resection: where is the limit? Surgery 1992;111:251-9. 4. Huguet C, Gavelli A, Bona S. Hepatic resection with ischemia of the liver exceeding one hour. J Am Coll Surg 1994;178:454-8. 5. Nagasue N, Yukaya H, Suehiro S, Ogawa S. Tolerance of the cirrhotic liver to normothermic ischemia: a clinical study in 15 patients. AmJ Surg 1984;147:772-5. 6. Bismuth H, Castaing D, Garden OJ. Major hepatic resection under total vascular exclusion. Ann Surg 1989;210:13-9. 7. Edwards MJ, Bentley FR. Major hepatic resection under total vascular exclusion with extracorporeal venovenous bypass. Am Surg 1994;60:231-3. 8. Elias D, Desruennes E, Lasser P. Prolonged intermittent clamping of the portal triad during hepatectomy. Br J Surg 1991; 78:424. 9. Ezaki T, Seo Y, Tomoda H, Furusawa M, Kanematsu T, Sugimachi K. Partial hepatic resection under intermittent hepatic inflow occlusion in patients with chronic liver disease. Br J Surg 1992;79:224-6. 10. Favi P, Valeri A, Presenti L, Tonelli P, Lucchese M, Massimo C. L'esclusione vascolare totale del legato con o senza ischemia addominale per l'esecuzione di resezioni epatiche maggiori: Fisiopatologia, tecnica chirurgica e risnltati. Chirurgqa 1991;4: 351-8. 11. Lazorthes F, Chiotasso P, Chevreau P, Materre JP, Roques J. Hepatectomy with initial suprahilar control of intrahepatic portal pedicles. Surgery 1993;113:103-8. 12. Matsmnata T, Kanematsu T, Shirabe K, et al. Modified technique of Pringle's maneuver in resection of the liver. Surg Gynecol Obstet 1991;172:245-6. 13. Hug~aet C, Stipa F, Gavelli A. Extended left hepatectomy with vascular exclusion. J Am Coll Surg 1994;178:288-92. 14. Okuda K, Nakayama T, Taniwaki S, et al. A new technique of hepatectomy using an occlusion balloon catheter for the hepatic vein. AmJ Surg 1992;163:431-4. 15. Sejourne P, Poirier A, MeakinsJL, et al. Effect of haemodilution on transfusion requirements in liver resection. Lancet 1989; 2:1380-2. 16. Smadja C, ILahwaji F, Berthoux L, Grange D, Franco D. Int6rfit du clampage p~diculaire total darts tes ex6r& h~patiques pour carcinome h6pato-cellulaire chez le cirrhotique. Ann Chir 1987;41:639-42. 17. Yan~aokaY, Ozawa K, Kumada K, et al. Total vascular exclusion for hepatic resection in cirrhotic patients: application of venovenous bypass. Arch Surg 1992;127:276-80. 18. Nagasue N, Yukaya H, Ogawa Y, Hirose S, Okita M. Segmental and subsegmental resections of the cirrhotic liver under hepatic inflow and outtlow occlusion. BrJ Surg 1985;72:565-8. 19. Pringle,lH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:54l-9. 20. Kim YI, Kobayashi M, Aramaki M, Nakashima K. Liver resection pertbrmed under prolonged portal triad occlusion in patients with active chronic liver diseases. Jpn J Surg 1994;24:328-32. 21. Terblanche J, Krige JEJ, Bornman PC. Simplified hepatic resection with the use of prolonged vascular inflow occlusion. Arch Surg 1991;126:298-301. 22. Couinand C. Le foies: Etudes anatomiques et chirurgicales. Paris: Masson, 1957. 23. Bismuth H. Les h6patectomies. In: Encycl M6d Chir. Paris: Techniques chirurgicales, 1978:4.2.07, 40762. 24. Bismuth H. Technique de l'h&patectomie droite. In: Encycl M6d Chir. Paris: Techniques chirurgicales, 1978:4.2.07, 40763. 25. Bismuth H. Technique de l'h6patectomie gauche. Encycl M6d Chir. Paris: Techniques chirurgicales, 1978:4.2.07, 40764.
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26. Gozzetti G, MazziottiA, Jovine E, et al. Esperienza su 400 resezioni epatiche. Chirurgia 1992;5:398-408. 27. Jamieson GG, Corbel L, Campion JP, Lannois B. Major liver resection without a blood transfusion: is it a realistic objective?Surgery 1992;112:32-6. 28. Maetani S, Nishikawa T, Hirakawa A, Tobe T. Role of blood transfusion in organ system failure fbllowing major abdominal surgery. Ann Surg 1986;203:275-81. 29. Stephenson KR, Steinberg SM, Hughes KS, VettoJT, Sugarbaker PH, Chang AE. Perioperative blood transfiasions are associated with decreased time to recurrence and decreased survival after resection of colo-rectaI liver metastases. Ann Surg i988;208:67987. 30. Tartter PI, Burrows L, Kirshner P. Perioperative blood transfusion adversely affects prognosis after resection of stage I (subset No.) non-oat cell lung cancer. J Thorac Cardiovasc Surg 1984; 88:659-62.
Surgery November 1996 31. Tartter PI, Burrows L, Papatestas AE, et al. Perioperative blood transfhsion has prognostic significance for breast cancer. Surgery 1985;97:225-30. 32. Woogt PJ, Van der Yelde CJH, Brand A, et al. Perioperative blood transfusion and cancer prognosis: different effects of blood transfusion on prognosis of colon and breast cancer patients. Cancer 1987;59:836-43. 33. Piccinni P, Notli ML, Bassi N, et al. Modificazione dei valori emodinamici in corso di chirurgia resettiva del fegato eseguita in clampaggio dell'ilo secondo Pringle. Chirurgia 1990;3:264-8. 34. Gavelli A, Jobard J, Huguet C. Mauvaise tolerance h6modinamiques/t l'exclusion vasculaire dn fbie: Neuf fois sur quaranteneuf eas. Lyon Chir 1994;90:367-70. 35. Bismuth H, Houssin D, Marmarian G. Postoperative liver insufficiency: prevention and management. WorldJ Surg 1983;7:50510.
Surgery is abstracted a n d / o r i n d e x e d in Index Medicus, Science Citation Index, Current Contents/ Clinical Medicine, Current Contents/LiJe Sciences, Excerpta Medica, a n d MEDLINE. This J o u r n a l has b e e n registered with Copyright Clearance Center, Inc., 222 Rosewood Dr., Danvers, MA 01923. C o n s e n t is given for the copying o f articles for p e r s o n a l or internal use o f specific clients. This c o n s e n t is given o n the condition that the copier pay directly to the C e n t e r the per-copy fee stated o n the first page o f each article for copying b e y o n d that p e r m i t t e d by U.S. Copyright Law. This c o n s e n t does n o t e x t e n d to o t h e r kinds o f copying, such as for general distribution, resale, advertising a n d p r o m o t i o n a l purposes, or for creating new collective works. All inquiries regarding copyrighted material f r o m this publication o t h e r t h a n those that can be h a n d l e d t h r o u g h Copyright Clearance C e n t e r should be d i r e c t e d to Associate J o u r n a l Publisher, Permissions, Mosby-Year Book, Inc., 11830 Westline Industrial Dr., St. Louis, M O 63146; p h o n e (314)579-2808; fax (314)432-1380.
Background. Reduction of operative blood transfusions is a primary goal in resective surgery of the liver. Tempormy vascular inflow occlusion is an effective method to decrease hemorrhage during hepatic resection. This study was performed to assess the impact of normothermic ischemia on intraoperative bleeding and outcome after hepatic resection. Methods. Sixty-one hepatic resections were performed by using pedicle clamping alone or associated with total vascular exclusion of the livet: The mean duration of normothermic isehemia was 40 +- 18 minutes O'ange, 7 to 98 minutes). Major resections were performed in 32 cases (52.5 %). Results. Operative mortality was nil. Major complications occurred in 11.5 % of cases. Twenty-five patients (41%) received intraoperative blood transfusions; mean +_ SD of transfused blood units was 2.4 + 1.3. Twelve major resections (3Z5 %) did not require any transfusion. Postoperative changes in liver function test results wei'e moderate and transient. Conclusions. The results of this study confirm the benefit of vascular occlusion techniques in reducing" intraoperative bleeding and postoperative complications. The routine use of these techniques during hepatic resections, if applied properly and with the necessary precautions, is not associated with severe adverse effects on liver function. (Surgery 1996;120:852-8.) From the Departments of Gedat,ic Surgery and of Anesthesiology, Catholic UniversityMedical School, Rome, Italy
OPERATIVE MORTALITYAND MORBIDITYofhepatic resection
have b e e n significantly r e d u c e d in r e c e n t years; however, bleeding remains the most i m p o r t a n t intraoperatire risk factor. T h e demonstration of a g o o d tolerance of the liver to n o r m o t h e r m i c ischemia, even for prolonged periods o f time, 1-5 has p e r m i t t e d the use of various techniques of hepatic ischemia to reduce the entity of intraoperative h e m o r r h a g e and to e n h a n c e the resectability rate of neoplastic lesions, z' 6-17 It has b e e n shown that hepatic pedicle clamping (HPC) is a safe technique to control bleeding from intraparenchymal portal mad arterial pedicle branches.5, 9, 16, 18, 19 This m a n e u v e r has been used generally in emergency, and at present it is also applied as a routine maneuver during liver resection and also in cirrhotic liver.24, 9, zo, 21 However, the routine use of HPC is n o t widely accepted because of the fear of adverse hemodynamic effects a n d o f i s c h e m i c damage to the liver, particularly in patients with liver cirrhosis or with o t h e r causes o f i m p a i r m e n t o f hepatic function. 12 Total vascular exclusion (TVE) of the liver is necessary to Accepted for publication April 4, 1996. Reprint requests: Gennaro Nuzzo, MD, Cattedra di Chirurgia Geriatrica, Universit~ Cattolica del S. Cuore, L.go Agostino Gemelli, 8 - 00168 Roma, Italy. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00 + 0 852
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control suprahepatic caval bleeding, which is the most i m p o r t a n t cause o f concern during hepatic resection, a n d to resect lesions close to the vena cava o r to the suprahepatic caval confluence. 5-7' 17 The aim o f this study was to evaluate the influence of hepatic ischemia obtained by routine use of HPC, alone or associated with caval clamping (TVE), on postoperative o u t c o m e in 61 patients who u n d e r w e n t hepatic resection.
METHODS Between April 1989 and May 1995, 61 liver resections were p e r f o r m e d u n d e r hepatic n o r m o t h e r m i c ischemia. T h e 27 m e n a n d 32 women (two female patients u n d e r w e n t reresection) h a d a m e a n age o f 56 - 15 years (range, 2 to 76 years). In 47 cases (77%) the indications for liver resection were malignant tumors; the m o r e frequent ones were metastases from colorectal cancer (24 cases). Liver cirrhosis (Child-Pugh class A) was present in 9 patients; 14 patients h a d u n d e r g o n e preoperative systemic chemotherapy. In 14 cases (23%) liver resection was perf o r m e d for benign liver disease. In Table I the indications for hepatic resection are listed in detail. A major liver resection (that is, a resection o f at least three segments) was p e r f o r m e d in 32 cases (52.5%). As defined by C o u i n a u d ' s liver anatomy, zz 3 right e x t e n d e d hepatectomies, 1 left e x t e n d e d hepatectomy, 11 right hepatectomies, 6 left hepatectomies, 10 resections o f
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T a b l e I. Indications for hepatic resection in 61 cases Malignant tumors Metastases From colorectal cancer From noncolorectal cancer Hepatocellular carcinoma Gallbladder carcinoma Hepatoblastoma Cholangiocarcinoma Hilar carcinoma Benign diseases Focal nodular hyperplasia Hydatid cyst Hemangioma Cysts Intrahepatic lithiasis Adenoma Abscess
47 (77%) 30 24 6 9 3 2 2 1 14 (23%) 4 3 2 2 1 1 1
three segments, a n d 1 resection o f four segments (III, IV, V, a n d VI) were p e r f o r m e d (Table II). In two cases a tangential resection o f the retrohepatic vena cava, with TVE, was associated with right hepatectomy. In 29 cases (47.5%) a m i n o r liver resection was performed. All patients were o p e r a t e d on electively and by the same surgeon (G.N.). Surgical exposure was always t h r o u g h a bilateral subcostal laparotomy enlarged with a sternal split. Parenchymal transection was d o n e by Kelly clamps, and hemobiliostasis was obtained by use o f transfixed sutures of thin reabsorbable material, according to the technique described by Bismuth. 23"25HPC was p e r f o r m e d systematically with a vascular tourniquet. Attention was paid to apply the tourniquet at a safe distance from the pancreas. In the presence o f a left hepatic artery coming from the gastric artery t h r o u g h the gastrohepatic ligament, such artery was also clamped. To reduce clamping time, the maneuver was started after the section of Glissonian's capsule and o f the superficial parenchymal layers. After completion o f the resection, inflow occlusion was released and any residual b l o o d or bile leaks were sutured. In eight cases TVE o f the liver was used (Table III). This r e q u i r e d careful isolation of the inferior vena cava, from the d i a p h r a g m to the renal veins. After the pedicle was c l a m p e d with a tourniquet, tile cava was closed below the liver with a De Bakey clamp (placed above the confluence with the right adrenal vein; alternatively this vein was divided and suture ligated). T h e n the cava was closed above the liver with a Satinsky clamp. In two o f these patients h e m o d y n a m i c tolerance to this technique was initially poor. In o n e patient the maneuver was tolerated after consistent b l o o d volume expansion with clTstalloids; in the o t h e r patient vascular exclusion
853
T a b l e II. Type o f resection in 61 cases Major resections Right hepatectomy Extended right hepatectomy (to segment IV) Left hepatectomy Extended left hepatectomy (to segments V and VIII) Resection of 3 segments Resection of 4 segments Minor resections Resection of 2 segments Resection of 1 segment Atypical resection
32 (52.5%) 11" 3 6 1 10 1 29 (47.5%) 18 9 2
* T a n g e n t i a l r e s e c t i o n o f r e t r o h e p a t i c v e n a cava i n 2 cases.
n e e d e d to be discontinued a n d the resection was p e r f o r m e d with pedicle clamping only. This corres p o n d e d to an intolerance rate to TVE o f 12%. Neither topical refrigeration n o r hypothermic liver perfusion was used. T h e average duration o f n o r m o t h e r m i c hepatic ischemia was 40 • 18 minutes (range, 7 to 98 minutes); in 13 patients (21%) ischemia was p r o l o n g e d for 60 minutes or more. In some instances, in patients older than 70 years of age, in patients with liver cirrhosis or jaundice, or in patients who previously u n d e r w e n t systemic chemotherapy, HPC was discontinued for 5 minutes every 10 to 15 minutes o f i s c h e m i a (10 patients). In one patient who u n d e r w e n t right hepatectomy with tangential caval resection, the surgeon d e c i d e d to proceed to caval resection after 45 minutes o f HPC. HPC was i n t e r r u p t e d for 10 minutes (impaired liver function from previous c h e m o t h e r a p y was also a cause o f concern in this patient), a n d then a TVE was p e r f o r m e d for 53 minutes. T h e total time o f liver ischemia was 98 minutes. At the e n d of the p r o c e d u r e o n e or two silicon drains were positioned in all patients. T h e mean d u r a t i o n o f the p r o c e d u r e was 291 • 108 minutes. Prophylaxis or postoperative treatment with anticoagulants was n o t used in any patient. To verify the influence of warm liver ischemia on postoperative course, the following factors was evaluated: perioperative mortality and morbidity rates, numb e r of patients who r e q u i r e d intraoperative b l o o d transfusions, n u m b e r of units transfused, time r e q u i r e d for operation, postoperative profiles of levels o f aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, p r o t h r o m b i n time, a n d total cholesterol, a n d postoperative stay. Results are r e p o r t e d as m e a n -+ SD. Comparisons were det e r m i n e d by using Student's t test; a p value below 0.05 was considered significant.
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T a b l e III. Features of patients who underwent TVE
Age (yr)
Disease
57
Colorectal cancer metastasis
58 39
Cholangiocarcinoma Retroperitoneal leiomyosarcoma metastases Colorectal cancer metastases Breast cancer metastases Anal cancer metastasis Colorectal cancer metastases
73 33 61 59
45
Colorectal cancer metastases
Resection
Ischemia time (rain)
TVE time (rain)
Complications
Right hepatectomy + tangential caval resection Right hepatectomy Bisegmentectomy
75
40
Pleural effusion (with thoracentesis)
54 42
23 35
Moderate liver failure --
Left hepatectomy
50
NT*
Left hepatectomy + atypical resections Extended left hepatectomy Right hepatectomy + tangential caval resection
60
5
80
20
98
53
52
7
Right hepatectomy
Severe liver failure, subphrenic abscess, pleural effusion (with thoracentesis)
*NT, N o t tolerated.
T a b l e IV. Morbidity in 61 hepatic resections (overall morbidity of 12 cases [19.7%])
Type of complication Major (7 cases* [11.5%]) Severe liver failure Biliary fistula Subphrenic abscess Minor (5 cases* [8.2%]) Moderate liver failure Pneumonia Pleural effusion (with thoracentesis)
3 3 3 2 3 2
*3 cases with m o r e than one complication.
RESULTS
Overall operative mortality in this group of patients was nil. Postoperative complications were observed in 12 cases (19.7%), none of which required a reoperation. Major complications occurred in seven cases (11.5%) and minor complications occurred in five cases (8.2%) (Table IV). Five patients experienced postoperative liver failure. Two of them (including a 73-year-old patient with cirrhosis) had only postoperative ascites and total bilirubin elevation below 3 m g / d l (moderate liver failure). The other three patients experienced severe liver failure (encephalopathy, persistent jaundice, ascites); all of them had undergone resection for malignant disease with a duration of hepatic ischemia of 40, 68, and 98 minutes, respectively. A major liver resection was per-
tormed in two of them; in one case, subphrenic abscess and pleural effusion, treated with thoracentesis, were also associated. A minor resection was performed in the third patient, who had metastases from retroperitoneal leiomyosarcoma; this patient, who had already undergone resection 16 months before and had received subsequently multiple cycles of systemic chemotherapy, also had a subphrenic abscess. Pleural effusion occurred in 15 cases (25 %), but it was considered to be a complication only when a thoracentesis was required (2 patients). In patients in w h o m TVE was used, total morbidity rate was 37.5%, but major complications developed only in one patient (12.5%) (Table III). Postoperative morbidity rate in 13 cases with liver ischemia lasting more than 1 hour (30.8%) was not significantly higher compared with the remainder with liver ischemia lasting less than 1 hour (16.7%). In the former group 12 patients (92%) had undergone a major resection. Age older than 65 years, presence of cirrhosis, preoperative systemic chemotherapy, extent of hepatic resection, and ischemia longer than 1 hour were not associated with significantly higher morbidity rates (Table V). Twenty-five (41%) patients received intraoperative blood transfusions (Table VI) In these the average of transfused blood units was 2.4 + 1.3 units (range, 1 to 6 units); however, six of these patients received only 1 blood unit. Twelve major resections (37.5%) were performed without any blood transfusion. Three patients (43%) who underwent hepatic resection with TVE did not receive any blood transfusion.
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T a b l e V. Morbidity in relation to specific factors Complicated cases Total
n
%
Overall morbidity 61 Age (yr) >65 17 <65 44 Cirrhosis Yes 9 No 52 Preoperative chemotherapy Yes 14 No 47 Resection Major 32 Minor 29 Ischemia (hr) >1 13 <1 48
12
19.7
2 10
11.8 22.7
1 11
11.1 21.2
3 9
21.4 19.1
8 4
25.0 13.8
4 8
30.8 16.7
A significant increase ofAST, ALT (ALT > AST), total bilirubin, and conjugated bilirubin a n d a significant fall of p r o t h r o m b i n time a n d total cholesterol, comp a r e d with preoperative values, were n o t e d on postoperative day 1; in most instances values t e n d e d to r e t u r n to n o r m a l ranges within 1 week, except for ALT values (Table VII). Patients with an hepatic ischemia of 60 minutes o r m o r e h a d wider alterations of biochemical values with respect to patients with a less p r o l o n g e d ischemia, b u t the general t r e n d toward the n o r m a l values was similar (Table VIII). The patients in whom severe postoperative liver thilure developed had significantly greater hematochemical abnormalities on postoperative day 1 c o m p a r e d w i t h the variations observed in the remainder. Moreover, in this g r o u p the trend o f the hematochemical values to return toward n o r m a l ranges was significantly delayed; bilirubin a n d total cholesterol were the latest values to r e t u r n to n o r m a l ranges (Table IX). Overall m e a n postoperative stay was 18 -+ 14 days. DISCUSSION T h e reduction of operative blood loss and, consequently, o f the n u m b e r o f transfusions is considered a primary goal in resective surgery of the live r ) ' 2, 6, 13, 18, 21, 26-28 It has been shown that, independ e n t of the risk of transmission of viral diseases and o f i m m u n e reactions, operative mortality and morbidity rates are affected by the n u m b e r of b l o o d transfusions. 2s F u r t h e r m o r e , several authors have emphasized that the long-term results of surgery for neoplastic diseases are m o r e satisfactory in patients who did n o t receive b l o o d transfusions. 29-32 This last issue is of particular interest
855
T a b l e VI. Intraoperative b l o o d transfusions in 61 cases n
Total Resection Major Minor TVE Yes No
Transfused cases n (%)
Units of blood (range)
61
25 (41)
2.4 - 1.3 (1-6)
32 29
20 (62.5) 5 (17.2)
2.5 -+ 1.4 (1-6) 2.0 -+ 0.6 (1-3)
7* 54
4 (57) 21 (38.9)
3.7 - 1.5 (2-6) 2.1 -+ 1.0 (1-5)
*One patient did not tolerate TVE and was excluded.
if one considers that malignant tumors are the m o r e c o m m o n indication for liver resection; in o u r series malignancies r e p r e s e n t e d 77.1% of the indications for surgery. T e m p o r a r y vascular inflow occlusion of the liver represents an easy technique to reduce the risk o f b l e e d i n g d u r i n g hepatic resections. Even if the efficacy a n d the safety of the pedicle clamping, as described by Pringle 19 in 1908, for p r o l o n g e d periods o f time a n d in cirrhotic livers are already well d o c u m e n t e d , 1-5' 13, 21, 33 controversies still exist a b o u t the tolerance of the liver to warm ischemia. Since April 1989 the use of hepatic pedicle clamping (HPC) has b e e n i n c l u d e d in our r o u t i n e app r o a c h to liver resection. At the m o m e n t we consider the n e e d to p e r f o r m simultaneously a colon resection a n d the presence o f d e e p j a u n d i c e as relative contraindications to the use of this technique. In the first instance we tend to avoid pedicle clamping because of the risk of vascular p r o b l e m s a n d e d e m a to the colon anastomosis. In the case o f d e e p j a u n d i c e liver function is already severely c o m p r o m i s e d a n d the application of techniques of vascular occlusion has to be limited to emergency situations only. Clamping o f the cava below a n d above the liver associated with HPC allows TVE o f the liver and also permits control of h e m o r r h a g e from hepatic veins or from the inferior vena cava. With the use o f TVE it is possible to p e r f o r m hepatic resections in patients with large or posterior tumors, r e d u c i n g the risk of bleeding. This technique is well tolerated in most patients. < 6, 34 In our experience interruption o f TVE was necessary only in one case. T h e results of our analysis confirm the efficacy of techniques o f vascular occlusions such as HPC a n d TVE. As a matter of fact in this series with more than 50% of major resections, almost 60% o f the p r o c e d u r e s was p e r f o r m e d without any b l o o d transfusion. In addition, in transfused patients the a m o u n t of transfused b l o o d was very limited (2.4 -+ 1.3 units [i.e., 720 -+ 390 ml]), a n d six o f these patients received only 1 b l o o d unit. Use o f these m e t h o d s o f vascular occlusion reduces
856
Nuzzo et al.
Surgery November 1996
T a b l e V I I . Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s o n 58 p a t i e n t s *
Preoperative AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) P r o t h r o m b i n time (%)
31.0 42.5 0.7 0.3 189.8 93.5
• 25.1 • 64.0 _+ 0.7 -+ 0.4 • 37.7 • 12.4
Day 1 409.4 468.1 1.8 0.6 117.2 58.7
~+ 345.5 _+ 365.0 + 1.3 + 0.5 + 29.9 + 19.3
Day 3 86.0 241.2 1.3 0.5 125.5 75.1
+ 97.7 -+ 232.3 -+ 1.0 + 0.7 + 34.6 +_ 18.6
Day 7 41.2 118.0 1.3 0.7 125.4 80.5
• 24.9 • 88.3 _+ 1.5 • 1.3 • 47.0 • 15.1
Values are nrean _+ SD. Day 1 versus p r e o p e r a t i v e values, p < 0,05. *Patients with severe postoperative liver failure were e x c l u d e d f r o m this evaluation.
T a b l e V I I I , Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s i n r e l a t i o n to liver i s c h e m i a t i m e
Preoperative
Day 1
Day 3
Day 7
i
<1 h r AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%) >1 h r AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%)
33.0 46.6 0.8 0.3 188.2 92.9
• • • + • +
27.0 69.8 0.8 0.5 35.9 12.2
358.8 421.4 1.7 0.5 116.2 60.0
_+ 278.3 _+ 308.6 _+ 1.4 _+ 0.5 _+ 30.1 _+ 20.0
66.9 202.9 1.2 0.5 129.7 76.4
_+ 50.4 -+ 187.5 -+ 0.9 • 0.5 -+ 34.3 -+ 18.5
36.7 110.1 1.1 0.4 126.3 82.2
_+ 15.0 +_ 83.4 _+ 0.9 +- 0.5 _+ 51.1 -+ 14.1
22.6 25.4 0.6 0.1 197.1 96.2
• 11.9 • 21.5 -+ 0.2 • 0.1 -+ 44.6 -+ 13.2
616.4 658.9 1.9 0.9 121.4 54.5
_+ 487.4 _+ 493.5 _+ 0.8 • 0.7 _+ 28.7 _+ 16.3
162.4 394.4 1.6 0.9 111.0 70.8
• 173.8 -+ 315.8 • 1.4 • 1.1 + 31.6 • 18.2
54.6 140.7 1.9 1.4 123.1 78.0
• + + + • +
39.4 97.5 2.6 2.3 35.4 16.0
Values are m e a n • SD. Day 1 versus preoperative values, p < 0.05. Patients who h a d severe postoperative liver failure were e x c l u d e d from this evaluation.
T a b l e I X . Liver f u n c t i o n test results b e f o r e a n d a f t e r h e p a t i c r e s e c t i o n s i n 3 p a t i e n t s w i t h severe p o s t o p e r a t i v e liver failure
Preoperative AST (units/L) ALT (units/L) Total bilirubin (mg/dl) Conjugated bilirubin (mg/dl) Cholesterol (mg/dl) Prothrombin time (%)
22.3 20.33 0.5 0.1 167.0 93.7
-+ 0.9 _+ 3.1 -+ 0.2 _+ 0.1 _+ 32.3 _+ 12.5
Day 1 1593.3 • 1476.7 + 3.7 • 1.7.• 88.3 • 36.7 +
809.0 1116.1 1.3 0.2 28.6 8.7
Day 3 312.7 704.3 5.8 3.1 81.3 45.8
• 136.1 • 522.6 + 2.4 • 1.2 +- 35.5 _+ 8.6
Day 7 67.33 199.7 8.2 5.3 96.0 69.0
_+ 26.7 + 107.7 • 4.5 • 3.1 • 28.1 • 9.9
Vahles are m e a n _+ SD.
p o s t o p e r a t i v e m o r b i d i t y r a t e also by allowing a m o r e acc u r a t e surgical t e c h n i q u e . I n fact, w i t h inflow v a s c u l a r o c c l u s i o n it is p o s s i b l e to w o r k i n a b l o o d l e s s o p e r a t i v e field a n d t h e r e f o r e a m o r e a c c u r a t e h e m o s t a s i s a n d b i b iostasis c a n b e p e r f o r m e d , I n this series overall m o r b i d ity r a t e was less t h a n 2 0 % a n d m a j o r c o m p l i c a t i o n s w e r e o b s e r v e d i n only s e v e n p a t i e n t s ( 1 1 . 5 % ) ; n o n e o f t h e s e required a reoperation. Liver failure is a p o s t o p e r a t i v e c o m p l i c a t i o n specifically r e l a t e d to h e p a t i c r e s e c t i o n . 35 T h e o c c u r r e n c e o f this c o m p l i c a t i o n is r e l a t e d to t h e a m o u n t a n d to t h e
f u n c t i o n a l a d e q u a c y o f tile r e s i d u a l liver p a r e n c h y m a ; cirrhosis is t h e c o n d i t i o n m o r e a t risk. I n this s t u d y we obseiwed severe p o s t o p e r a t i v e liver failure i n t h r e e patients. I n all o f t h e m t h e d u r a t i o n o f i s c h e m i a was l o n g e r t h a n 40 m i n u t e s . F o r two o f t h e m s o m e p r e o p e r a t i v e i m p a i r m e n t o f liver f u n c t i o n c o u l d b e i m p l i c a t e d bec a u s e o f p r o l o n g e d systemic c h e m o t h e r a p y ; o n e p a t i e n t u n d e r w e n t r i g h t h e p a t e c t o m y w i t h v e n a cava r e s e c t i o n , a n d t h e o t h e r o n e u n d e r w e n t r e r e s e c t i o n o f two segments. The third patient underwent right hepatectomy e x t e n d e d to s e g m e n t IV a n d r i g h t a d r e n a l e c t o m y .
Surgery Volume 120, Number 5
T h e s e o b s e r v a t i o n s c o n f i r m t h a t t h e risk o f p o s t o p e r a tive liver f a i l u r e is e n h a n c e d , as a l r e a d y r e p o r t e d by o t h e r a u t h o r s , 4 by t h e c o m b i n a t i o n o f p o s t c h e m o t h e r apy h e p a t i c d a m a g e , p r o l o n g e d liver i s c h e m i a , a n d extensive r e s e c t i o n . I n t h e g r o u p o f p a t i e n t s w i t h c i r r h o s i s a m o d e r a t e deg r e e o f liver failure was o b s e r v e d o n l y in o n e case a f t e r r i g h t h e p a t e c t o m y f o r h e p a t o c a r c i n o m a . Also i n t h e s e p a t i e n t s t h e use o f H P C p e r m i t t e d p e r f o r m a n c e o f liver r e s e c t i o n w i t h o u t b l o o d t r a n s f u s i o n s in 4 4 % o f t h e cases, a n d in t h e t r a n s f u s e d p a t i e n t s t h e n u m b e r o f b l o o d u n i t s (2.4 + 1.5) was s i m i l a r to t h a t o f p a t i e n t s w i t h o u t cirrhosis (2.4 -+ 1.3). T h e low m o r b i d i t y r a t e o b s e r v e d in p a t i e n t s w i t h c i r r h o s i s (12.5%) was likely a result of both an accurate preoperative selection of the p a t i e n t s a n d a m e t i c u l o u s p r e p a r a t i o n f o r surgery. W i t h r e g a r d to t h e t e c h n i c a l safety o f t h e s e v a s c u l a r o c c l u s i o n t e c h n i q u e s , n o specific c o m p l i c a t i o n o f H P C o r TVE was o b s e r v e d , s u c h as i n j u r y to biliary o r vascular structures o f p o r t a l pedicle o r to inferior v e n a cava. It s h o u l d b e m e n t i o n e d t h a t particular a t t e n t i o n was p a i d to p u t t h e t o u r n i q u e t for pedicle c l a m p i n g away f r o m t h e p a n c r e a s a r o u n d t h e s u p e r i o r t h i r d o f t h e pedicle. T h e g o o d t o l e r a n c e o f t h e liver to i s c h e m i a was c o n f i r m e d in this s t u d y by a n a l y z i n g p o s t o p e r a t i v e variat i o n s o f liver f u n c t i o n test results. B i o c h e m i c a l evaluation of hepatic fnnction did not show any relevant or persistent variations in patients with ischemia lasting more than 1 hour or in patients with ischemia lasting less t h a n 1 h o u r . T h e t r e n d o f r e t u r n t o w a r d n o r m a l r a n g e s was significantly a l t e r e d o n l y i n t h e p a t i e n t s w h o h a d severe p o s t o p e r a t i v e liver failure. A n a s p e c t t h a t d e s e r v e s f u r t h e r i n v e s t i g a t i o n is t h e possibility o f r e c o g n i z i n g early i n p o s t o p e r a t i v e c o u r s e t h e p a t t e r n s t h a t a r e p r e d i c t i v e o f t h e s u b s e q u e n t d e v e l o p m e n t o f liver failu r e ; this m a y h e l p d i s c r i m i n a t e e a r l i e r t h e p a t i e n t s w i t h a greater need for careful monitoring and supportive care. I n c o n c l u s i o n , t h e results in this study c o n f i r m t h e u s e f u l n e s s o f v a s c u l a r o c c l u s i o n t e c h n i q u e s d u r i n g resective s u r g e r y o f t h e liver. T h e s e t e c h n i q u e s allow us to m i n i m i z e i n t r a o p e r a t i v e b l e e d i n g with t h e n e e d f o r b l o o d t r a n s f u s i o n s a n d allow a m o r e c a r e f u l o p e r a t i v e t e c h n i q u e w i t h a low r a t e o f p o s t o p e r a t i v e c o m p l i c a tions. I n a d d i t i o n , T V E m a y c o n t r i b u t e to i n c r e a s i n g t h e i n d i c a t i o n s f o r s u r g e r y f o r lesions at h i g h risk o f b l e e d ing. T h e results also s h o w t h a t u s e o f H P C a n d TVE, w h e n c a r r i e d o u t p r o p e r l y a n d with t h e n e c e s s a r y p r e c a u t i o n s , is n o t a g g r a v a t e d b y u n b e a r a b l e adverse effects o n liver f u n c t i o n . REFERENCES
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