Liver resection as a bridge to transplantation for hepatocellular carcinoma on cirrhosis: a reasonable strategy?

OBJECTIVE: To assess the viability of a strategy of primary resection with secondary liver transplantation (LT) for hepatocellular carcinoma (HCC) on cirrhosis. SUMMARY BACKGROUND DATA: LT is the optimal treatment of HCC with cirrhosis. Owing to organ shortage, liver resection is considered as a reasonable first-line treatment of patients with small HCC and good liver function, with secondary LT as a perspective in case of recurrence. The viability of such strategy, positively explored in theoretical models, is not documented in clinical practice. METHODS: Among 358 consecutive patients with HCC on cirrhosis treated by liver resection (n = 163; 98 of whom were transplantable) or transplantation (n = 195), the feasibility and outcome of secondary transplantation was evaluated in a 2-step fashion. First, secondary LT for tumor recurrence after resection (n = 17) was compared with primary LT (n = 195), to assess the risk and the outcome of secondary LT in patients who effectively succeeded to be treated by this approach. Second, primary resection in transplantable patients (n = 98) was compared with that of primary LT (n = 195) on an intention-to-treat basis, to assess the outcome of each treatment strategy and to determine the proportion of resected patients likely to be switched for secondary LT. Transplantability of resected patients was retrospectively determined according to selection criteria of LT for HCC. RESULTS: Operative mortality (< or =2 months) of secondary LT was significantly higher than that of primary LT (28.6% versus 2.1%; P = 0.0008) as was intraoperative bleeding (mean transfused blood units, 20.7 versus 10.5; P = 0.0001). Tumor recurrence occurred more frequently after secondary than after primary LT (54% versus 18%; P = 0.001). Posttransplant 5-year overall survival was 41% versus 61% (P = 0.03), and disease-free survival was 29% versus 58% (P = 0.003) for secondary and primary LT, respectively.Of 98 patients treated by resection while initially eligible for transplantation, only 20 (20%) were secondarily transplanted, 17 of whom (17%) for tumor recurrence and 3 (3%) for hepatic decompensation. Transplantability of tumoral recurrence was 25% (17 of 69 recurrences). Compared with primarily transplanted patients, transplantable resected patients had a decreased 5-year overall survival (50% versus 61%; P = 0.05) and disease-free survival (18% versus 58%; P < 0.0001), despite the use of secondary LT.On a multivariate analysis including 271 patients eligible for transplantation and treated by either liver resection or primary LT, liver resection alone (P < 0.0001; risk ratio [RR] = 3.27) or liver resection with secondary LT (P < 0.05; RR= 1.87) emerged as negative independent factors of disease-free survival as compared with primary LT. A number of nodules > 3 (P = 0.002; RR= 2.02) and a maximum tumor size exceeding 30 mm (P < 0.0001; RR=1.93) were also predictive of lower disease-free survival. CONCLUSIONS: LT after liver resection is associated with a higher operative mortality, an increased risk of recurrence, and a poorer outcome than primary LT. In addition, liver resection as a bridge to LT impairs the patient transplantability and the chance of long-term survival of cirrhotic patients with HCC. Primary LT should therefore remain the ideal choice of treatment of a cirrhotic patient with HCC, even when the tumor is resectable.     

Geographical and temporal distribution of human giardiasis in Ontario,Canada

Background  

Giardia is the most frequently identified intestinal parasite in North America. Although information on geographical distribution of giardiasis is critical in identifying communities at high risk, little has been done in this area. Therefore, the objective of this study was to investigate the geographical and temporal distribution of human giardiasis in Ontario in order to identify possible high risk areas and seasons. Two spatial scales of analyses and two disease measures were used with a view to identifying the best of each in assessing geographical patterns of giardiasis in Ontario. Global Moran's I and Moran Local Indicators of Spatial Associations were used to test for evidence of global and local spatial clustering, respectively.     

Developing evidence-based ethical policies on the migration of health workers: conceptual and practical challenges

It is estimated that in 2000 almost 175 million people, or 2.9% of the world's population, were living outside their country of birth, compared to 100 million, or 1.8% of the total population, in 1995. As the global labour market strengthens, it is increasingly highly skilled professionals who are migrating. Medical practitioners and nurses represent a small proportion of highly skilled workers who migrate, but the loss of health human resources for developing countries can mean that the capacity of the health system to deliver health care equitably is compromised. However, data to support claims on both the extent and the impact of migration in developing countries is patchy and often anecdotal, based on limited databases with highly inconsistent categories of education and skills.     

Assessing human resources for health: what can be learned from labour force surveys?

Background  

Human resources are an essential element of a health system's inputs, and yet there is a huge disparity among countries in how human resource policies and strategies are developed and implemented. The analysis of the impacts of services on population health and well-being attracts more interest than analysis of the situation of the workforce in this area. This article presents an international comparison of the health workforce in terms of skill mix, sociodemographics and other labour force characteristics, in order to establish an evidence base for monitoring and evaluation of human resources for health.     

The association of autosomal dominant optic atrophy and moderate deafness may be due to the R445H mutation in the OPA1 gene

PURPOSE: To examine the involvement of the optic atrophy 1 (OPA1) gene in optic atrophy associated with moderate deafness. DESIGN: Observational case report.The entire coding sequence of the OPA1 gene was directly sequenced in the case of a patient suffering from optic atrophy associated with moderate deafness. RESULTS: A de novo heterozygous mutation R445H in the OPA1 gene was found. No similar mutation was detected in either of the patient's parents or in the 100 chromosome controls. CONCLUSION: The R445H mutation in OPA1 might be the cause of the association between dominant optic atrophy and moderate deafness, a phenotype that may be currently underdiagnosed.     

Involvement of central muscarinic receptors in social and nonsocial learning in sheep

Within 12 h following parturition, ewes develop visual and auditory recognition of their lamb. To investigate whether central cholinergic muscarinic transmission plays a specific role in this social learning, we studied the effects of a muscarinic antagonist on neonate recognition via visual/auditory cues and acquisition of a nonsocial visual discrimination. Injections of scopolamine (100 microg/kg; a muscarinic antagonist crossing the blood-brain barrier) after birth did not affect maternal behavior but impaired visual/auditory recognition of the offspring. Recognition impairment did not occur in mothers treated with methylscopolamine (100 microg/kg; a peripheral muscarinic antagonist), indicating that central muscarinic transmission is specifically involved in this social learning. Similar doses of scopolamine strongly delayed learning of a nonsocial, visual discrimination task in comparison to either control or methylscopolamine-treated ewes. Performance on this task was not affected when scopolamine treatment was applied after learning, demonstrating that central muscarinic receptors are necessary for acquisition but not for retrieval. These results suggest that the central muscarinic transmission participates in the establishment of visual/auditory recognition of conspecifics. Moreover, activation of central muscarinic receptors is critical for learning regardless of the social properties of the stimulus.     

ETA,mixed ETA/ETB receptor antagonists,and protein kinase C inhibitor prevent acute hypoxic pulmonary vasoconstriction: influence of potassium channels

The aims of this study were to investigate the effects of a selective ETA (BQ-123), a selective ETB (BQ-788), and a specific mixed ETA/ETB receptor antagonist (bosentan) on the pulmonary vasoconstriction induced by hypoxia in the isolated perfused rat lung, and the role of nitric oxide, adenosine triphosphate-sensitive (KATP), large conductance Ca+-activated (BKCa) and 4-aminopyridine-sensitive voltage-gated K channels (K+) in the relaxant effects of the selective ETA receptor antagonist BQ-123 and a protein kinase C inhibitor, bisindolylmaleimide I. K+ channels were inhibited by glibenclamide, charybdotoxin, and 4-aminopyridine and nitric oxide synthase by L-NG-nitroarginine methyl ester (L-NAME). Hypoxic ventilation produced a significant pressure response (+57%, p < 0.001). BQ-123, bosentan, and bisindolylmaleimide I induced a concentration-dependent decrease of the hypoxic pressure response (p < 0.001), whereas BQ-788 did not exhibit any inhibitory effect against hypoxic pressure response. Glibenclamide, charybdotoxin, and 4-aminopyridine partially opposed the inhibitory effects elicited by BQ-123 (p < 0.05), but L-NAME did not modify these effects. The effects of bisindolylmaleimide I on hypoxic pressure response were unaffected by glibenclamide, charybdotoxin, or 4-aminopyridine. The authors conclude that (a) ETA receptors and protein kinase C are involved in the modulation of hypoxic pulmonary vasoconstriction; and (b) the ETA antagonist BQ-123 opposes hypoxic pulmonary vasoconstriction through KATP, KV, and BKCa channels, differing in this from the protein kinase C inhibitor bisindolylmaleimide I. These results suggest that BQ-123 operates through a mechanism independent of bisindolylmaleimide I-inhibited protein kinase C isoforms.     

Effects of multimicronutrient supplementation on helminth reinfection: a randomized,controlled trial in Kenyan schoolchildren

A randomized, placebo-controlled, double-blind, two-by-two factorial trial was carried out among 977 schoolchildren from 19 primary schools in Nyanza Province, Kenya from February 1995 to February 1996. The interventions were multimicronutrient supplementation (vitamin A, 1000 micrograms; vitamin B1, 1.4 mg; vitamin B2, 1.6 mg; vitamin B6, 1.7 mg; vitamin B12, 2.0 micrograms; folate, 150 micrograms; niacin, 16 mg; vitamin C, 50 mg; vitamin D, 5 micrograms; vitamin E, 8 mg; iron, 18 mg; zinc, 20 mg; copper, 2.0 mg; iodine, 150 micrograms; selenium, 40 micrograms) and multihelminth chemotherapy (albendazole 600 mg in a single dose and/or praziquantel 40 mg/kg in a single dose). This paper reports the effects of the supplementation given on all school days on reinfection with hookworm, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mansoni after 11 months. Baseline prevalence and geometric mean intensity for hookworm, A. lumbricoides, T. trichiura and S. mansoni in all children investigated were 54.7%, 13.8%, 45.6% and 70.0%, respectively and 8.6, 2.7, 5.9 and 19.4 eggs per gram (epg), respectively. Children received a mean of 2.3 multimicronutrient/placebo tablets per school week, giving a compliance rate of 46%. Children given multimicronutrients had a slightly, but significantly, lower intensity of S. mansoni reinfection compared with children given placebo (5.5 epg vs. 7.7 epg, P = 0.047). Multiple linear regression analyses controlling for baseline infection status confirmed this, as children who received micronutrients were reinfected with S. mansoni at only 69% of the intensity of those who received placebo. Multiple logistic regression analyses revealed that micronutrient supplementation was associated with a lower S. mansoni reinfection rate (odds ratio = 0.7) although this was only of borderline significance (P = 0.090). There were no significant differences in reinfection rates or intensities of hookworm, A. lumbricoides and T. trichiura. The effect on S. mansoni infection intensity is particularly interesting given the low compliance, suggesting that full micronutrient supplementation might have a role to play in S. mansoni control programmes.     

Toxicity of chemicals to microalgae in river and in standard waters

The influence of the composition of natural waters on the toxicity of chemicals to microalgae was studied on samples representative of western European rivers. Effects of zinc, pentachlorophenol (PCP), 4-nonylphenol (4-NP), phosalone, and 2,4,5-trichloroaniline (TCA) on algal growth were tested in river waters without adding any nutrients or cosolvents, and in the International Standards Organization (ISO) medium for comparison. The mean values of effective concentrations reducing the algal growth by 50% (EC50s) after 72 h based on measured concentrations did not differ significantly in natural waters and in standard medium for 4-NP (0.5 mg/L) and phosalone (0.8-0.9 mg/L). These values were two or three times higher in rivers than in ISO medium for PCP (0.25 vs 0.1 mg/L), TCA (1.69 vs 0.73 mg/L), and zinc (0.20 vs 0.056 mg/L). Although the mean values were of the same order of magnitude, the distribution of the EC50 values ranged over 1.5 and 2 log concentrations in surface waters. Therefore, in view of a refined hazard assessment of a chemical on a local scale, it would be advisable to use the actual river water of the concerned aquatic environment in testing. Correlations between toxicity data and the physicochemical characteristics of the waters identified classic parameters such as water hardness or conductivity as factors that significantly influenced the toxicity of the ionizable compounds PCP and zinc. On the other hand, organic materials or suspended solids, but only at high levels, affected the toxicity of 4-NP, an organic chemical with high adsorption potential. No correlation could be drawn for phosalone and TCA.