Parenchymal Function Research Articles

Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life

Respiratory dysfunction in adults has been correlated with neonatal Chlamydia trachomatis pneumonia in several studies, but a causal association has not been clearly demonstrated. In this study, we examined radial alveolar counts (RACs) by microscopy, and airway and parenchymal lung function using a small animal ventilator in juvenile (5 weeks age) and adult (8 weeks age) BALB/c mice challenged as neonates with Chlamydia muridarum (C. mur) on day 1 or day 7 after birth, representing saccular (human pre-term neonates) and alveolar (human term neonates) stages of lung development, respectively. Pups challenged with C. mur on either day 1 or 7 after birth demonstrated significantly enhanced airway hyperreactivity and lung compliance, both as juveniles (5 weeks age) and adults (8 weeks age), compared with mock-challenged mice. Moreover, mice challenged neonatally with Chlamydia displayed significantly reduced RACs, suggesting emphysematous changes. Antimicrobial treatment during the neonatal infection induced early bacterial clearance and partially ameliorated the Chlamydia-induced lung dysfunction as adults. These results suggest that neonatal chlamydial pneumonia, especially in pre-term neonates, is a cause of respiratory dysfunction continuing into adulthood, and that antimicrobial administration may be partially effective in preventing the adverse respiratory sequelae in adulthood. The results of our studies also emphasize the importance of prenatal screening and treatment of pregnant women for C. trachomatis in order to prevent the infection of neonates.

Sectionectomy of the liver

Anatomic resection of the liver, which refers to the systemic elimination of the main tumor with micrometastases, preserves liver function and is highly recommended. Tumors located centrally or in the vicinity of major portal pedicles or hepatic veins, however, tend to require extensive hepatectomy. Anatomic sectionectomy of the liver might represent an alternative to such extensive resection. Preoperative simulation, external landmarks, selective devascularization, and intraoperative ultrasound are useful to achieve anatomic sectionectomy. Anatomic resection requires division of the relevant portal vein, hepatic artery, and bile duct. This may be achieved by individual isolation of the three elements or by mass isolation of all three in their surrounding fibrous sheath (Glisson's capsule). Both approaches are equally effective for extensive resections. When sectionectomy is performed, however, the isolation of individual vasculobiliary elements is sometimes difficult and dangerous compared with the isolation of the sectional portal pedicles. By identifying the portal pedicles to individual anatomic sections, it is possible to control the inflow to the section that is intended for resection. Anatomic sectionectomy is a safe alternative to extensive liver resection in selected patients, avoiding unnecessary sacrifice of functional liver parenchyma and increasing the opportunity to perform repeat resections in cases of recurrence.

Severely impaired cerebrovascular reserve in patients with cerebral proliferative angiopathy

Cerebral proliferative angiopathy (CPA) has been morphologically distinguished from classically appearing brain arteriovenous malformations (AVMs) by exhibition of functional brain parenchyma that is intermingled with abnormal vascular channels. The presence of oligemia in this intralesional brain tissue may suggest ischemia, which is not detected in classic brain AVMs. The authors hypothesized that patients with CPA would exhibit a greater impairment of cerebrovascular reserve in neuronal tissue surrounding the true nidus compared with those with brain AVMs. Four patients with CPA, 10 patients with brain AVMs and seizures, and 12 young healthy individuals were studied. The 4 patients with CPA underwent blood oxygen level-dependent MR imaging examinations while applying normoxic step changes in end-tidal CO(2) to obtain quantitative cerebrovascular reactivity measurements. Patients with a CPA lesion exhibited severely impaired perilesional cerebrovascular reserve in comparison with patients with brain AVMs and seizures (0.10 ± 0.03 vs 0.16 ± 0.03, respectively; p < 0.05), and young healthy individuals (0.10 ± 0.03 vs 0.21 ± 0.06, respectively; p < 0.01). This study demonstrated severely impaired cerebrovascular reserve in the perilesional brain tissue surrounding the abnormal vessels of patients with CPA. This finding may provide an additional means to distinguish CPA from classic brain AVMs.

Equine multinodular pulmonary fibrosis in horses in the UK

EQUINE multinodular pulmonary fibrosis (EMPF) is a relatively recently described condition in horses, characterised by a loss of functional pulmonary parenchyma due to extensive nodular to coalescing interstitial fibrosis; the...

Morphological and functional analyses of two infants with obstructive renal dysplasia

Renal dysplasia associated with urinary tract obstruction comprises two distinct phenotypes, i.e., multicystic dysplastic kidney (MCDK) and obstructive renal dysplasia (ORD). MCDK is a common manifestation in infants with renal dysplasia, which is characterized by multiloculated thin-walled cysts with no functional parenchyma and an atretic ureter owing to pyelocalyceal occlusion early in fetal life. In contrast, ORD is an extremely rare condition which is caused by severe obstruction of the distal ureter or urethra. Here, we report two infants with ORD. Both patients manifested unilateral kidney enlargement with multiple cortical cysts, mild hydronephrosis, and marked dilatation of the ipsilateral ureter. Contralateral kidneys and urinary tracts revealed no apparent radiological abnormalities. Serial ultrasonographic studies of fetal and neonatal kidneys in both cases revealed that ureteral dilatation was evident at gestational week 16 and 27, respectively, and most of the cortical cysts disappeared within 1-3months after birth. The functions of the affected kidneys were severely impaired but evident at the time of birth. These manifestations were consistent with a diagnosis of ORD, and were distinct from the features of MCDK. Our observation of fetal and infantile kidneys in these two cases provides us with a better understanding of the pathogenesis of ORD.

Acute liver failure secondary to opportunistic viral infection in adult solid organ transplant recipients

Acute liver failure (ALF) is the product of a rapid, overwhelming insult to the liver that destroys parenchymal function, resulting in a multisystem illness characterized by coagulopathy and encephalopathy. Viral infections and drug induced liver injury are the most common causes of ALF.1 The most common viral precipitants are the hepatotropic viruses, hepatitis A, B and E (ALF due to hepatitis C is rare outwith the context of liver transplantation). Defective cell-mediated immunity is associated with increased susceptibility to viral hepatitis; reactivation of hepatitis B may occur in those receiving chemotherapy or immunosuppression2 while hepatitis E follows a more severe course in pregnant women and is reported to cause chronic hepatitis in organ transplant recipients.3 Systemic viral infections such as herpes viruses (Epstein–Barr virus, cytomegalovirus, herpes simplex), parvovirus and adenovirus can also affect the liver. In immunocompetent hosts they usually cause a mild collateral hepatitis, but in immunosuppressed individuals, impaired immune surveillance may result in secondary visceral infection, which if severe, may precipitate ALF.4 We describe two fatal cases of ALF due to opportunistic non-hepatotropic viral infections in adult solid organ transplant recipients. A 46-year-old female cardiac transplant recipient was admitted with fever and dyspnoea. She had received a heart transplant 10 months earlier for complications of congenital heart disease and was receiving mycophenolate mofetil (MMF) and cyclosporine immunosuppression. While there was no obvious site of infection, she was commenced on broad spectrum antibiotics following a full sepsis screen (which included bacterial cultures and viral serology), and her immunosuppression was reduced. Liver enzymes were mildly deranged at the time of admission with an ALT of 57 IU/l. Her condition deteriorated over the following 48 h with the development of severe hepatitis (ALT 1919 IU/l and INR 1.4) and renal impairment, which prompted her transfer to the …

The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus

Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.

Extent of Liver Resection for Hilar Cholangiocarcinoma (Klatskin Tumor): How Much Is Enough?

Background: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. Methods: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. Results: The majority of resections (78%) were performed for Bismuth type III–IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. Conclusion: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%.

Reversibility of Hepatic Histological Damage after Surgical Temporary Obstruction of the Common Bile Duct in a Murine Model

The reversibility of hepatic histological damage after restoring bile flow in a murine model was assessed. 25 male Balb C mice (25-35 g, age 6 weeks) were divided into 5 groups and their common bile duct (CBD) fastened to obstruct the release of gall bladder and liver contents. Group I, CBD untied at day 10, group II at day 15, and groups III and IV at days 20 and 30, respectively. Hematoxilin-eosin stained liver slices were analysed 0, 5, 10 and 20 days after restoring bile flow. Group I showed slight histological lesions (second stage), as cholangiolar bile pigment concretion, pericholangiolar and portal collagen accumulation; group II, mild lesions (third stage), as cholangiolar hamartomatous proliferation and bile duct portal fibrosis; group III showed severe lesions (fourth stage), as loss of functional parenchyma, and also the second and first stage lesions. Group IV died before 30 days. First stage corresponds to absent lesions (control group). Group I recovered totally, group II recovered only from slight lesions and group III had irreversible damage. Severity of lesions increased gradually and accumulatively, irreversible hepatic damage was achieved at 20 days and is deadly at 30 days. Our model of temporary CBD obstruction was suitable to assess reversibility of hepatic histological damage.

For better or for worse: the immune response against Mycobacterium tuberculosis balances pathology and protection

Tuberculosis (TB) is a complex disease, and the success of the bacterium as an intracellular pathogen is the outcome of its close and longstanding coevolution with the mammalian host. The dialogue between Mycobacterium tuberculosis and the host is becoming understandable at the molecular, cellular, and tissue level. This has led to the elucidation of the (i) interaction between pattern recognition receptors and pathogen-associated molecular patterns, (ii) cross-talk between immune cells, and (iii) mechanisms underlying granuloma development. Disease as an eventual but not a necessary consequence of infection results from a sensitive balance between protective immunity and destructive pathology. Early events, governed largely by conserved mechanisms of host recognition, impact not only on type and course of adaptive immunity but also on lung parenchymal function. New interpretations of how these responses shape the lung environment and direct granuloma development emphasize that the disease results from pathologic consequences of non-resolving inflammation. We review recent advances in TB research within the context of this ambitious view of TB.

The origin of interstitial myofibroblasts in chronic kidney disease

Chronic kidney diseases (CKD), independent of their primary cause, lead to progressive, irreversible loss of functional renal parenchyma. Renal pathology in CKD is characterized by tubulointerstitial fibrosis with excessive matrix deposition produced by myofibroblasts. Because blocking the formation of these scar-forming cells represents a logical therapeutic target for patients with progressive fibrotic kidney disease, the origin of renal myofibroblasts is a subject of intense investigation. Although the traditional view holds that resident fibroblasts are the myofibroblast precursor, for the last 10 years, injured epithelial cells have been thought to directly contribute to the myofibroblast pool by the process of epithelial-to-mesenchymal transition (EMT). The recent application of genetic fate mapping techniques in mouse fibrosis models has provided new insights into the cell hierarchies in fibrotic kidney disease and results cast doubt on the concept that EMT is a source of myofibroblast recruitment in vivo, but rather point to the resident pericyte/perivascular fibroblast as the myofibroblast progenitor pool. This review will highlight recent findings arguing against EMT as a direct contributor to the kidney myofibroblast population and review the use of genetic fate mapping to elucidate the cellular mechanisms of kidney homeostasis and disease.

Laparoscopic Heminephrectomy of a Horseshoe Kidney

Minimally invasive surgery has revolutionized surgery for urologic disorders, and laparoscopic procedures have become widely available for several different ablative and reconstructive operations. Laparoscopic heminephrectomy in patients with horseshoe kidney can be a technically challenging procedure due to aberrant vessels, functional parenchyma in the isthmus, and abnormal location. We report the management of a case of symptomatic nonfunctioning left moiety of a horseshoe kidney with emphasis on its surgical technique combined with a review of the literature. Laparoscopic heminephrectomy is a feasible option in the surgical management of benign and malignant conditions of the horseshoe kidney and can be performed safely using a transperitoneal or a retroperitoneal approach.

Comments on Instrumentation in Neurosurgery

Modern neurosurgery has a brief history of around 100 years. It is called “modern” because its development has been associated with the tremendous progress of modern science and technology. Sharp tools do good work. The introduction of the microscope brought neurosurgery into the era ofmicroneurosurgery, and use of the endoscope has further minimized surgical invasiveness in selected cases. Progress in neurology has made it possible to locate neurologic lesions more accurately. Not only the lesion itself, but also the surrounding vasculature, affected nerves, nucleus and tracts, and functional brain parenchyma are well mapped. The Visual Reality system, which employs three-dimensional image merging techniques, enables the neurosurgeon to make a detailed surgical plan. The neuronavigation system, a great innovation in neurosurgery, has helped neurosurgeons to perform operations with proper orientation. The introduction of intraoperative magnetic resonance imaging (MRI) has eliminated the worry about brain shift during operation. We have used 3.0 T intraoperative MRI for months and find it is of precious value in performing glioma resection to achieve “maximal safe resection.” Furtherprogress shouldbe focused on definitive mapping of brain functional areas, including the motor, sensory, hearing, and visual functional areas and the ways they interact. Resting MRI investigation is valuable in solving positional problems. Brain activity can be evaluated not only by BOLD (blood oxygen level-dependent) techniques but also by physical electric activity and neurotransmitter change, which cannot be well shown with images of high resolution. During vascular surgery, blood flowmonitoring, such as intraoperative digital subtraction angiography, angiography using indocyaninegreendye, andDopplerultrasound, andbrainmonitoring, such as neuroelectrophysiologic monitoring, brain tissue partial pres-

Lung and vascular function during chronic severe pulmonary ischemia.

Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. In rats as well as higher mammals, severe pulmonary ischemia results in bronchial vascular proliferation. Using labeled microspheres, we demonstrated an 18-fold increase in systemic blood flow to the ischemic left lung. Additionally, vascular remodeling extended to the tracheal venules, which showed an average 28% increase in venular diameter. Despite this increase in vascularity, airways resistance was not altered nor was methacholine responsiveness. Since these measurements include the entire lung, we suggest that the normal right lung, which represented 78% of the total lung, obscured the ability to detect a change. When functional indexes such as diffusing capacity, in situ lung volume, and vascular permeability of the left lung could be separated from right lung, significant changes were observed. Thus when comparing average left lung values of rats 14 days after left pulmonary artery ligation to left lungs of rats undergoing sham surgery, diffusing capacity of the left lung decreased by 72%, left lung volume decreased by 38%, and the vascular permeability to protein increased by 58%. No significant differences in inflammatory cell recruitment were observed, suggesting that acute ischemic inflammation had resolved. We conclude that despite the preservation of lung tissue, the proliferating bronchial neovasculature may contribute to a sustained decrement in pulmonary function.

Luminal platelet aggregates in functional deficits in parenchymal vessels after subarachnoid hemorrhage

The pathophysiology of early ischemic injury after aneurysmal subarachnoid hemorrhage (SAH) is not understood. This study examined the acute effect of endovascular puncture-induced SAH on parenchymal vessel function in rat, using intravascular fluorescent tracers to assess flow and vascular permeability and immunostaining to assess structural integrity and to visualize platelet aggregates. In sham-operated animals, vessels were well filled with tracer administered 10 s before sacrifice, and parenchymal escape of tracer was rare. At ten minutes and three hours after hemorrhage, patches of poor vascular filling were distributed throughout the forebrain. Close examination of these regions revealed short segments of narrowed diameter along many profiles. Most vascular profiles with reduced perfusion contained platelet aggregates and in addition showed focal loss of collagen IV, a principal component of basal lamina. In contrast, vessels were well filled at 24 h post-hemorrhage, indicating that vascular perfusion had recovered. Parenchymal escape of intravascular tracer was detected at 10 min post-hemorrhage and later as plumes of fluorescence emanating into parenchyma from restricted microvascular foci. These data demonstrate that parenchymal microvessels are compromised in function by 10 min after SAH and identify focal microvascular constriction and local accumulation of luminal platelet aggregates as potential initiators of that compromise.

A chronic outcome of shock wave lithotripsy is parenchymal fibrosis

Shock wave lithotripsy (SWL) is widely viewed as an effective noninvasive method to break stones within the kidney and ureter. However, it is a technology that is not without trauma to the kidney--acute vascular, tubular and interstitial damage is often reported that if severe enough can lead to renal fibrosis (scarring) and permanent loss of functional parenchyma. These chronic changes can potentially lead to serious long-term adverse effects. The risk of developing chronic fibrotic lesions after lithotripsy is influenced by the number of shock waves (SWs) administered, SW power, rate of SW delivery and the number of SWL treatment sessions. The interplay between these risk factors is largely unknown, but progress has been made in identifying SWL protocols and pharmacologic therapies that can ameliorate the acute and chronic tissue damage that is an unintended consequence of SWL treatment.

Luminal endothelial lectins with affinity forN-acetylglucosamine determine flow-induced cardiac and vascular paracrine-dependent responses

Coronary blood flow applied to the endothelial lumen modulates parenchymal functions via paracrine effectors, but the mechanism of flow sensation is unknown. We and others have demonstrated that coronary endothelial luminal membrane (CELM) oligosaccharides and lectins are involved in flow detection, and we proposed that cardiac effects of coronary flow result from a reversible flow-modulated lectin-oligosaccharide interaction. Recently, glycosylated and amiloride-sensitive Na(+)/Ca(++) channels (ENaCs) have been proposed to be involved in the flow-induced endothelial responses. Because N-acetylglucosamine (GlcNac) is one of the main components of glycocalyx oligosaccharides (i.e., hyaluronan [-4GlcUAbeta1-3GlcNAcbeta1-](n)), the aim of this article is to isolate and define CELM GlcNac-binding lectins and determine their role in cardiac and vascular flow-induced effects. For this purpose, we synthesized a 460-kDa GlcNac polymer (GlcNac-Pol) with high affinity toward GlcNac-recognizing lectins. In the heart, intracoronary administration of GlcNac-Pol upon binding to CELM diminishes the flow-dependent positive inotropic and dromotropic effects. Furthermore, GlcNac-Pol was used as an affinity probe to isolate CELM GlcNac-Pol-recognizing lectins and at least 35 individual lectinic peptides were identified, one of them the beta-ENaC channel. Some of these lectins could participate in flow sensing and in GlcNac-Pol-induced effects. We also adopted a flow-responsive and well-accepted model of endothelial-parenchymal paracrine interaction: isolated blood vessels perfused at controlled flow rates. We established that flow-induced vasodilatation (FIV) is blocked by endothelial luminal membrane (ELM) bound GlcNac-Pol, nitro-l-arginine methyl ester and indomethacin, amiloride, and hyaluronidase. The effect of hyaluronidase was reversed by infusion of soluble hyaluronan. These results indicate that GlcNac-Pol inhibits FIV by competing and displacing intrinsic hyaluronan bound to a lectinic structure such as the amiloride-sensitive ENaC. Nitric oxide and prostaglandins are the putative paracrine mediators of FIV.

Locoregional Therapy

Even after complete surgical resection of pulmonary metastases, many patients develop recurrent disease in the thorax despite the use of systemic chemotherapy, dosage of which is limited because of systemic toxicity. Although subsequent operations are feasible and good long-term results have been reported, sufficient functional lung parenchyma must remain. For this reason, new treatment strategies are explored. Similar to isolated limb and liver perfusion, isolated lung perfusion (ILuP) is a promising surgical technique for the delivery of high-dose chemotherapy with minimal systemic toxicity. The use of biologic response modifiers, such as tumor necrosis factor, is also feasible. ILuP with high-dose chemotherapy has proven to be highly effective in the experimental models of pulmonary metastases with a superior survival advantage compared with systemic treatment. Lung levels are significantly higher after ILuP compared with intravenous therapy without systemic exposure. Phase I human studies have shown that ILuP is technically feasible with low morbidity and without compromising the patient's pulmonary function. Further clinical studies are necessary to determine its definitive effect on local recurrence, long-term toxicity, pulmonary function, and survival.

Undetectable late hepatic sequelae after hypofractionated stereotactic radiotherapy for liver tumors

Hypofractionated liver stereotactic radiotherapy has produced long-term survival, but the hepatobiliary system is radiosensitive and may be severely damaged by the treatment. We have evaluated long-term radiation effects on hepatobiliary functions in the first long-term survivors reported after radiotherapy to the hepatobiliary system for liver tumors. Eleven patients were followed for up to 13 years after treatment of tumors≤9 cm in size. Conventional blood chemistry, clearance of indocyanine green and segmental uptake and excretion of radiolabeled mebrofenin were assayed. Slightly abnormal routine blood chemistry was found during the first 2 years in some patients with pre-existing liver damage. Other parameters were seemingly unaffected, and liver segments which received differing mean doses did not differ measurably with regard to parenchymal or ductal function. Late liver functions were therefore not demonstrably affected by the radiotherapy in most patients even in the presence of mild cirrhosis, after previous exposure to liver toxic agents, or after resection. However, slight to moderate late dysfunction occurred in one patient after three courses of irradiation, and in a cirrhotic patient after two major liver resections following radiotherapy. Our previous doses for irradiation of liver tumors gave no measurable chronic side effects and may be increased in order to control tumors more effectively. In selected patients, irradiation is possible even in the presence of liver dysfunction, and previous irradiation or resection does not absolutely contraindicate salvage treatment by re-irradiation or resection.

How to assess liver function?

The liver comprises a multitude of parenchymal and nonparenchymal cells with diverse metabolic, hemodynamic and immune functions. Available monitoring options consist of 'static' laboratory parameters, quantitative tests of liver function based on clearance, elimination or metabolite formation and scores, most notably the 'model for end-stage liver disease'. This review aims at balancing conventional markers against 'dynamic' tests in the critically ill. There is emerging evidence that conventional laboratory markers, most notably bilirubin, and the composite model for end-stage liver disease are superior to assess cirrhosis and their acute decompensation, while dynamic tests provide information in the absence of preexisting liver disease. Bilirubin and plasma disappearance rate of indocyanine green reflecting static and dynamic indicators of excretory dysfunction prognosticate unfavorable outcome, both, in the absence and presence of chronic liver disease better than other functions or indicators of injury. Although dye excretion is superior to conventional static parameters in the critically ill, it still underestimates impaired canalicular transport, an increasingly recognized facet of excretory dysfunction. Progress has been made in the last year to weigh static and dynamic tests to monitor parenchymal liver functions, whereas biomarkers to assess nonparenchymal functions remain largely obscure.