Preoperative Assessment of Liver Function

Halki Diabetes Remedy

Diabetes Holistic Treatment

Get Instant Access

Many elements contribute to the optimal selection of patients who will undergo surgery for hilar cholangiocarcinoma, including:

- Improvement of the preoperative diagnosis in the definition of size, site and tumour extent related to intrahepatic vascularisation

- Findings of the intraoperative workup

- Knowledge of the biological behavior of the tumour

- Effects of biliary obstruction and jaundice

- Effects of parenchymal inflammatory process and of cholangitis on clinical course and prognosis

- Nutritional state

- Adjuvant therapy

The choice of resection must take into consideration the need to remove the tumour completely as well as the need to maintain residual volume of parenchyma to carry on hepatic function.

In surgery of hilar cholangiocarcinoma, which also requires extended resection, attention must be focused not only on the amount of hepatic parenchyma removed but mainly to the residual quantity and its ability to guarantee acceptable postoperative residual liver function. Depending on the type of growth, cholangiocarcinoma can bring about complete or selective obstruction of one or more segments of the intrahepatic biliary tree. The obstacle to bile flow is responsible for worsened global hepatic function with a major risk of septic phenomena and relevant systemic effects. In presence of biliary obstruction, biliary pressure increases from 5-10 to 30 cm of H2O with destruction of the junctions between hepatocytes and biliary cells. The results are: (1) compression by dilated biliary tract on capacity portal vessels with reduction of portal flow; (2) negative influence on humoral factors involved in initiating and maintaining the regeneration with a decrease in growth-related factors; (3) activation of hepato-cellular apoptosis process by accumulation of toxic bile salts; (4) increased cholangiole permeability with direct bile reflux in sinusoids and beginning of inflammatory response; (5) decreased bile excretion by hepatocytes; (6)

decreased excretory activity of hepatocytes with a direct reflux of metabolites in circulatory system and consequent systemic toxicity; (7) alteration of micro- and macro-vascular perfusion.

Protide synthesis is altered with albumin level reduction, alteration of coagulation factors and a fall in immunoglobulins. The effects of obstruction extend to detoxification activity of the liver with decreased excretion of the substances metabolised in the liver. The systemic effects of biliary obstruction are evident with regard to cardiovascular activity, renal function, and the coagulation process. Jaundiced patients are more susceptible to developing postoperative shock consequent to depression of left ventricular activity and decreased peripheral vascular resistance as well as plasmatic volume. Renal function is impaired by hyperbilirubinemia, due to the reduction of renal perfusion related to cardiac pump impairment and to renal causes themselves, as natriuretic effects of bile salts and direct parenchymal toxicity of endotoxaemia; renal failure in jaundice patients has a mortality that can reach 70% [1]. Deprivation of bile at the intestinal level interferes with vitamin K absorption, with prolongation of prothrom-bin time. The effects of bile deprivation on the intestine and the interruption of enterohepatic circulation determine the loss of emulsive and antitoxic activity of bile salts, permitting the abundant amount of endotoxins present in the intestinal lumen to be absorbed by the portal circulation [2]. With a normal biliary pressure (7-14 cm of H2O) bacteremia in portal circulation is cleared by Kuppfer cells; in presence of biliary obstruction their activity is impaired with decreased bacterial and endotoxin clearance and antigen presentation. High concentration of bacteria in the bile and biliary hypertension are the causes of cholangitis and biliary sepsis. Decompression of the biliary system, with a normalisation of bilirubinemia values, produces such improvement of biochemical circulating parameters and hepatic function that it allows performance of extended hepate-ctomies with 70% hepatic volume resection without or with very low postoperative hepatic insufficiency [3-6]. Jaundice resolution is considered able to restore a hepatic reserve similar to that of patients with normal hepatic function [4]. However, external drainage does not restore enterohepatic circulation and does not affect bacterial translocation. Bile replacement has been proposed in jaundiced patients to repair intestinal mucosa integrity and reduce septic complications [7]. The need for preoperative drainage in patients with hilar cholangio-carcinoma is debated; in patients with cholangitis, long-term jaundice, severe malnutrition, and bilirubinemia >5 mg/ml, who require major hepatectomy (more than 60%), preoperative drainage is considered efficacious [8-11]. In the same way, biliary drainage of the future remnant liver is considered mandatory prior to performing PVE since expected hypertrophy requires normal values of bilirubinemia [12,13]. In all other cases of biliary obstruction there are two different schools of thought: Western thinking supports early resection in jaundiced patients with hilar cholangiocarcinoma, considering that biliary drainage presents the risk of complications (peritonitis, cholangitis, bleeding) from 3 to 5% [14,15]; also, the potential risk of neoplastic seeding, although rare, is consid ered able to jeopardise the radicality of surgery [16]. On the other hand, Asian authors support the use of biliary drainage [17,18] that is addressed to normalising liver function with an improvement of cholestatic liver tolerance to ischemia, to decrease transfusion therapy and to improve regeneration capacity. Clinical randomised trials have not shown until now that biliary drainage, internal or external, is of benefit prior to resection. Even the modalities of drainage (endoscopic/percutaneous, segmental/lobar, single/multiple, trans-stenotic or not) are under discussion and require further study. Unilateral biliary drainage should be used on the side of the future remnant liver. Drainage of atrophic liver is contraindicated due to unlikelihood of reversing hepatic volume and function loss from atrophy. Prior evaluation of resection of hepatic function and investigation of predictive factors to assess hepatic volume and the reserve of residual function are taken into consideration in order to reduce operative risk [19].

Tests that measure the serum value of hepatic enzymes are commonly defined standard liver function tests and reflect the hepatocytes' integrity or the presence of cholestasis. Albuminemia and prothrombin time are related to the functioning hepatic mass, but are not specific to hepatopathy [20]; although not unanimously recognised, a predictive value to the standard liver function test is not given until nowadays [21]. Child score, an indicator of excretion and synthesis function and portal hypertension utilised in the surgery of the cirrhotic liver, is not useful in cholangiocarcinoma in the non-cirrhotic liver. Many qualitative tests have been proposed using different substrates (Table 1); in spite of being precise, they are impractical in a clinical setting for various reasons such as excessive cost, need for multiple samples and prolonged catheterisation, and risk of allergic reaction.

Table 1 Quantitative tests. Adapted from [19]

Quantitative Tests Aminopyridine breath test Antipyridine clearance Caffeine clearance Lidocaine clearance (MEGX) Methacetin breath test Galactose elimination capacity (GEC) Low-dose galactose clearance Sorbitol clearance Indocyanine green disappearance Albumine synthesis Urea synthesis

Function Tested Microsomial function Microsomial function Microsomial function Microsomial function Microsomial function Cytosolic function Hepatic perfusion (liver blood flow) Hepatic perfusion (liver blood flow) Hepatic perfusion, anion excretion Synthetic function Synthetic function

The maximal enzymatic liver function capacity has been re-proposed based on the C-methacetin breath test (LiMAx test) [22]; it shows a significant correlation with remnant liver volume, but its recent introduction requires further validation. Of the proposed tests for anticipating the postoperative residual liver function, ICG clearance is considered the most powerful predictive test of operative mortality after hepatectomy if compared to other tests such as the aminoacid clearance test or aminopyrine breath test [23,24]. The model of retention rate (ICG-15) is the one most frequently used. The percentage of retention can be measured by pulsed spectrophotometry using an optical sensor [25]. There is no unanimous consensus on the cut-off value of IGC retention with a predictive value of postoperative hepatic failure, but it is believed that IGC-15 equal to or greater than 15% is indicative of inadequate clearance with limited hepatic reserve; therefore major hepatectomy is unwise. ICG and bilirubin bind to the same carrier in the transport phase in hepatocytes, determining a competitive inhibition. In patients with obstructive jaundice hyperbilirubinemia is independent of the reserve of hepatic function and ICG retention is therefore not valid. In these cases 99-m TC-GSA scintigraphy is proposed, which assumes the role of a quantitative test of hepatic function [19]. Scintigraphy with 99-m TC-GSA (diethylenetriamine-pentaacetic acid with galactosyl human serum albumin) is a dynamic technique that provides information on the density of specific receptors on the plasma membrane of hepatocytes, whose density directly reflects the functioning hepatic mass. The liver can tolerate considerable reduction of its volume since mechanisms of compensatory hypertrophy are activated, but inadequate hepatic volume after resection (small remnant liver volume) can have a negative influence on the postoperative course with the risk of hepatic failure. Two events can occur: (1) the residual volume of a normo-functioning liver can be insufficient for providing an adequate hepatic reserve; (2) the hepatic reserve can be reduced due to a concomitant pre-existing hepatocellular impairment (in the case of hilar cholangiocarcinoma, obstructed biliary tract with jaundice, steatosis, fibrosis, cirrhosis) even in presence of an apparently sufficient volume. Techniques of preoperative measurement of hepatic volume on CT scans have been introduced [26]. The volumetric findings of hepatic resection and transplantation have shown a close correlation between actual and CT-calculated volumes allowing a precise evaluation of each hepatic segment [27-29]. The minimal volume of residual liver after resection that can guarantee a normal function is at least 25-30% of the initial functioning liver. This percentage must be increased to 40% and more, in patients with chronic hepatic disease or who have undergone previous chemotherapy [28,30,31]. The acquisition of hepatic volumetry allows evaluation of the efficacy of the procedure as PVE addressed to initiate preoperatively the compensatory hypertrophy of the future remnant liver.

The presence of cirrhosis greatly affects hepatic regeneration, and as an indication for hepatic resection in the cirrhotic patient, is subject to debate.

Particular attention must be paid to steatosis; diabetic, obese and patients who have undergone previous chemotherapy are likely to develop steatosis. Insulin is considered a promoting factor of hepatic regeneration; diabetic and obese patients present insulin resistance with a risk of developing postoperative failure related to the degree of steatosis [32]. In presence of steatosis PVE is indicated, to optimise the hepatic reserve [33]. None of the tests used alone can recognise the individuals who can tolerate hepatic resection, or determine the amount of resection. Laboratory data, diagnostic and quantitative tests are integrated and contribute, together with the surgeon's opinion, to formulating the correct surgical indication [21]. Two elements, biliary drainage and portal vein embolisation, combined on the basis of bilirubinemia values and future remnant liver characteristics, in our opinion acquire a prominent value in the preopera-tive assessment (Fig. 1); they are also important for recovering sufficient hepatic function in the patient candidate for biliary-hepatic resection due to hilar cholangiocarcinoma.

Preoperative Lab Testing Form

Fig. 1 Flowchart of preoperative preparation of hepatic resection for hilar cholangiocarcino-ma. In presence of normal bilirubinemia, after ICG clearance, indication for PVE is taken on the assessment of volumetry of future remnant liver. In jaundiced patients biliary drainage allows normalisation of bilirubinemia with the possibility of performing PVE if future remnant liver is not sufficient. Modified from [3]

Fig. 1 Flowchart of preoperative preparation of hepatic resection for hilar cholangiocarcino-ma. In presence of normal bilirubinemia, after ICG clearance, indication for PVE is taken on the assessment of volumetry of future remnant liver. In jaundiced patients biliary drainage allows normalisation of bilirubinemia with the possibility of performing PVE if future remnant liver is not sufficient. Modified from [3]

Was this article helpful?

0 0
Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

Get My Free Ebook

Post a comment