Volume 73 - 2010 - Fasc.4 - Symposium
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which can develop in the course of chronic and acute liver disease. It is characterized by cognitive and motoric deficits of varying severity. HE is functional in nature, potentially reversible and is thought to reflect the clinical manifestation of a low-grade cerebral edema, which exacerbates in response to ammonia and other pre- cipitating factors, such as electrolyte disturbances, bleeding, infec- tions, high protein diet, diuretics and sedatives. The action of these rather heterogeneous factors integrates at the level of oxidative/nitrosative stress and astrocyte swelling, which is associ- ated with an oxidative/nitrosative stress response in the brain with consequences for signal transduction, neurotransmission, synaptic plasticity and oscillatory networks in the brain.
Manifest HE is diagnosed on the basis of clinical symptoms according to the West Haven criteria, whereas diagnosis of mini- mal HE requires psychometric or neurophysiological testings. Here objective and reproducible measures to assess HE severity, such as critical flicker frequency or evoked potentials are superior to paper pencil tests.
Identification and treatment of precipitating factors is the main- stay of HE therapy. Also intravenous ornithine aspartate, vegetable protein, oral branched chain amino acids, lactulose enemas and liver transplantation are considered to be effective. Whereas the efficacy of oral lactulose and non-resorbable antibiotics in the treatment of an acute HE attack is under debate, the beneficial effect of lactulose and rifaximin in the secondary HE prophylaxis has recently been established. (Acta gastroenterol. belg., 2010, 73, 457-464).
Hepatitis B and hepatitis C virus and chronic kidney disease
The most common cause of liver disease in patients with chron- ic kidney disease (CKD) remains infection by hepatitis B virus (HBV) and/or hepatitis C virus (HCV). The adverse effects of HBV and/or HCV infections upon survival in patients with CKD have been repeatedly confirmed. An excess risk of death in HBsAg positive or anti-HCV antibody-positive patients may be at least partially attributed to chronic liver disease with its attendant com- plications. A negative impact of HCV infection on survival after renal transplantation has been linked to extrahepatic complica- tions, including chronic glomerulonephritis, sepsis, chronic allo- graft nephropathy, post-transplantation diabetes mellitus, and abnormal metabolism of calcineurin-inhibitors. Transmission of HCV infection by grafts from HCV-infected donors has been unequivocally demonstrated. Registry analyses suggest that recip- ients of kidneys from anti-HCV antibody positive donors are at increased risk of mortality. Renal grafts from HCV-infected donors should be restricted to viremic anti-HCV positive recipients. Several drugs have been recently licensed for therapy of HBV infection but available data in patients with CKD is mostly limited to experience with lamivudine. The standard of care for hepatitis C infection in patients on regular dialysis is monotherapy with conventional interferon, according to recent guidelines. Only dire circumstances justify interferon use after renal transplantation. (Acta gastroenterol. belg., 2010, 73, 465-471).
Sepsis and cirrhosis : many similarities
Sepsis and cirrhosis are both characterised by a hyperdynamic state associated with a low systemic vascular resistance, and the release of many mediators. The haemodynamic characteristics are so similar that sepsis is difficult to recognise in cirrhotic patients. Nevertheless, the occurrence of sepsis in cirrhotic patients is associated with high mortality rates. The resemblance of the two conditions may be in part related to the common translocation of bacterial products in cirrhosis.
This article reviews the similarities and differences between sepsis and cirrhosis and defines the basis for the treatment of severe sepsis in cirrhotic patients. (Acta gastroenterol. belg., 2010, 73, 472-478).
Atypical indications for small bowel capsule endoscopy
Obscure bleeding remains the most important indication for small bowel capsule endoscopy, but some other small bowel diseases have also been studied. The aim of this paper is to provide an overview of the recent literature concerning atypical or rare indications for the small bowel capsule endoscopy. (Acta gastro- enterol. belg., 2010, 73, 479-483).
Radionuclide therapy for hepatocellular carcinoma
Aim : Several techniques for radionuclide therapy of hepatocel- lular carcinoma (HCC) have been developed. In this overview the available radionuclide treatment modalities for HCC are present- ed, with an emphasis on Yttrium-90 (90Y) microspheres.
Methods : We comment on the commercially available products and describe the practical aspects of these treatment modalities. Medical literature was screened for clinical data on these therapies in patients suffering from HCC. The most relevant studies are summarized, focusing on patient selection, safety and outcome.
Discussion : Randomized trials are still ongoing or recently ini- tialized. These trials will elucidate the role of 90Y-microspheres in relation to biotherapy and chemoembolization for palliative use in patients not amenable to surgery.
Conclusion : Large retrospective or cohort studies proof the safety of 90Y-microspheres for palliative use in HCC patients suffer- ing Child-Pugh A or B7 cirrhosis. Future research will yield more information on its efficacy when compared to chemoembolization or sorafenib. Several groups have reported on the use of selective internal radiation therapy (SIRT) for downstaging patients to sur- gical curative treatment. (Acta gastroenterol. belg., 2010, 73, 484- 488).
Angiographic considerations in patients undergoing liver-directed radio- embolization with 90Y microspheres
Catheter-directed, transarterial internal brachytherapy, using 90Y radioactive microspheres is gaining acceptance as a valuable treatment option in selected patients with liver malignancies. Knowledge of the radiological anatomy of the visceral arteries, including the variant anatomy of celiac trunk, superior mesenteric artery and end branches as well as technique and catheter skills for careful vessel occlusion prior to 90Y delivery are of major impor- tance to safely and efficiently treat patients with radioemboliza- tion. In this review article, normal vascular anatomy, common variants and influence of tumors on the feeding arteries will be discussed. Finally, techniques of pre-treatment vessel occlusion, technique of 90Y-administration and the added value of C-arm computed tomography during work-up and administration of radioactive microspheres will be described. (Acta gastroenterol. belg., 2010, 73, 489-496).
Accurate KRAS mutation testing for EGFR-targeted therapy in colorectal cancer : emphasis on the key role and responsibility of pathologists
Patients with metastatic colorectal cancer and KRAS mutation are unlikely to benefit from treatment with anti-EGFR antibodies, and testing for KRAS mutation in this setting is recommended. Pathologists have a crucial role in accurate testing for KRAS muta- tions, whether or not testing is performed in their own laboratory, as mutation analysis is performed on paraffin embedded tissue selected by the pathologists. The type of fixative used is a very important issue, as some fixatives do not allow molecular testing. Pathologists must select the most appropriate tumoral tissue block for KRAS mutation analysis and hence, must know the sensitivity of the KRAS mutation detection methodology utilized in their ref- erence laboratory. It is essential that they select a tissue block that contains enough percentage of viable tumour cells, as false negative results will occur when the sample is contaminated with high levels of nontumour elements. Pathologists not only have to recognize the area of invasive carcinoma and distinguish it from non-invasive neoplastic components, but also have to estimate the percentage of necrotic debris and nontumoural elements. For tests that require a high percentage of tumour cells, macrodissection before extraction of nucleic acids is often indicated. The primary pathologists in addition are responsible for preparation of the pathology report for the tissue block on which the KRAS mutation analysis was per- formed and should transmit the results to the requesting clinician. Pathologists should participate in a multidisciplinary oncologic consult to achieve correct interpretation of the results e.g. in case of potential false negative results. (Acta gastroenterol. belg., 2010, 73, 497-503).
Why should the gastroenterologist bother about obesity ? An oncologic point of view
The incidence of obesity worldwide has increased dramatically during recent decades. As a consequence, obesity and associated co-morbidities constitute a serious threat in public health. Substantial epidemiologic evidence indicates that obesity is associ- ated with increased risk of death, and increased incidence and pro- gression of several cancers. Particular attention will be brought here to digestive and liver cancers. Plausible mechanisms by which obesity might participate to increased promotion and progression of cancer will be developed including hyperinsulinemia, insulin resistance and the pro-oxidative pro-inflammatory milieu charac- terizing the metabolic syndrome. We will focus on the specific case of hepatocellular carcinoma since the highest increase in mortality in obese individuals has been observed for this malignancy. Epidemiological evidence will be reviewed. We will next attempt to offer explanation for the higher risk of HCC in obese individuals although, at this point in time, we have insufficient knowledge to point towards the preeminence of factors directly related to obesi- ty or more tightly linked to NASH itself, the underlying liver dis- ease. (Acta gastroenterol. belg., 2010, 73, 504-509).
Cirrhosis and malnutrition : assessment and management
Malnutrition, characterized by protein and energy deficiency, is considered the most prevalent complication of liver disease. The pathofysiology includes reduced food intake, maldigestion and malabsorption but also avoidable iatrogenic factors, such as pre- scribed fasting, frequent paracenteses and "liver-diets" poor in fat and protein. Liver insufficiency corresponds to a state of accelerat- ed starvation. The diminished glucose tolerance and low glycogen stores in cirrhotic patients result in a reduced availability of glu- cose as energy source. The prevalence of undernutrition depends upon the severity of the liver insufficiency and the method of nutri- tional assessment. The aim of the nutritional plan is to realize a suf- ficient oral diet which includes enough proteins and calories. Several extra calorie supplements are indicated to surmount the lack of available glucose. The evidence in support of branched chain amino acid supplements is limited. Salt intake should be moderately restricted in case of ascites. Nasogastric tube feeding is indicated when patients are unable to maintain an adequate oral intake. In case tube feeding is not possible, total parenteral nutri- tion may be necessary to maintain an anabolic state. (Acta gastro- enterol. belg., 2010, 73, 510-513.