Resection of Large Hepatocellular Carcinoma Using the Combination of Liver Hanging Maneuver and Anterior Approach

Background  

Resection of a large hepatocellular carcinoma (HCC) is difficult and is associated with a poor outcome. Herein we describe our experience with the use of a liver hanging maneuver (LHM) in conjunction with the anterior approach (AA) in patients with large HCC (>10 cm) and compare the perioperative outcome with the conventional method (CM) for hepatic resection.     

Nonmotor symptoms in Parkin gene‐related parkinsonism

The aim of the study was to explore the prevalence and differences of nonmotor symptoms (NMSs) in patients with young‐onset Parkinson's disease (YOPD) with and without mutations in the Parkin gene and late‐onset Parkinson's disease (LOPD). Twenty‐seven patients with YOPD and 27 with LOPD, as well as 16 patients with homozygous or compound heterozygote Parkin mutations filled in the nonmotor symptoms questionnaire, a 30‐item self‐completed questionnaire that addresses various NMSs. Overall, NMSs were more prevalent in YOPD (12.07 ± 3.9; P = 0.009) and LOPD (13.26 ± 5.8; P = 0.001) compared with Parkin mutation carriers (7.38 ± 4.2). Dribbling of saliva, vivid dreams, loss of smell, and urinary urgency were more prevalent in YOPD compared with Parkin mutation carriers. Only anxiety was more prevalent in the latter. Apart from anxiety, NMSs appear to be less prevalent in Parkin gene‐related parkinsonism. Although these results need further study, the presented data might be helpful in the clinical recognition of specific phenotypes and genotypes in YOPD. The data are in keeping with a different pathological disease process in Parkin gene‐related parkinsonism. © 2010 Movement Disorder Society     

Indian‐subcontinent NBIA: Unusual phenotypes,novel PANK2 mutations,and undetermined genetic forms

Neurodegeneration with brain iron accumulation (NBIA) is etiologically, clinically, and by imaging a heterogeneous group including NBIA types 1 [pantothenate kinase‐associated neurodegeneration (PKAN)] and 2 (PLA2G6‐associated neurodegeneration), neuroferritinopathy, and aceruloplasminaemia. Data on genetically defined Indian‐subcontinent NBIA cases are limited. We report 6 patients from the Indian‐subcontinent with a movement disorder and MRI basal ganglia iron deposition, compatible with diagnosis of an NBIA syndrome. All patients were screened for abnormalities in serum ceruloplasmin and ferritin levels and mutations in NBIA‐associated genes [pantothenate kinase 2 (PANK2), PLA2G6 and ferritin light chain (exon 4)]. We present clinical, imaging and genetic data correlating phenotype–genotype relations. Four patients carried PANK2 mutations, two of these were novel. The clinical phenotype was mainly dystonic with generalized dystonia and marked orobulbar features in the 4 adolescent‐onset cases. One of the four had a late‐onset (age 37) unilateral jerky postural tremor. His mutation, c.1379C>T, appears associated with a milder phenotype. Interestingly, he developed the eye‐of‐the‐tiger sign only 10 years after onset. Two of the six presented with adult‐onset levodopa (L ‐dopa)‐responsive asymmetric re‐emergent rest tremor, developing L ‐dopa‐induced dyskinesias, and good benefit to deep brain stimulation (in one), thus resembling Parkinson's disease (PD). Both had an eye‐of‐the‐tiger sign on MRI but were negative for known NBIA‐associated genes, suggesting the existence of further genetic or sporadic forms of NBIA syndromes. In conclusion, genetically determined NBIA cases from the Indian subcontinent suggest presence of unusual phenotypes of PANK2 and novel mutations. The phenotype of NBIA of unknown cause includes a PD‐like presentation. © 2010 Movement Disorder Society     

Clinical approach to diarrheal disorders in allogeneic hematopoietic stem cell transplant recipients

Diarrhea is a common complication of allogeneic hematopoietic stem cell transplant (HSCT), with an average incidence of approximately 40%-50%. A wide variety of etiologies can contribute to diarrhea in HSCT patients, including medication-induced mucosal inflammation, infections, graft-vs-host disease and cord colitis syndrome in umbilical cord blood transplant. Clinical manifestations can vary from isolated diarrheal episodes, to other organ involvement including pneumonia or myocarditis, and rarely multiorgan failure. The approach for diagnosis of diarrheal disorders in HSCT patients depends on the most likely cause. Given the risk of life-threatening conditions, the development of clinically significant diarrhea requires prompt evaluation, supportive care and specific therapy, as indicated. Serious metabolic and nutritional disturbances can happen in HSCT patients, and may even lead to mortality. In this review, we aim to provide a practical approach to diagnosis and management of diarrhea in the post-transplant period.     

Abnormalities in motor cortical plasticity differentiate manifesting and nonmanifesting DYT1 carriers.

A mutation in the DYT1 gene causes dominantly inherited childhood-onset primary dystonia, but intriguingly, only 30 to 40% of those who carry the mutation ever develop symptoms. We have used the unique model provided by this group of patients to investigate the hypothesis that abnormalities in brain plasticity underlie the pathophysiology of primary dystonia. We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects. Groups were age-matched. We compared the effect in these groups of subjects of repetitive transcranial magnetic stimulation (rTMS) delivered to the motor cortex, by assessing changes in corticospinal excitability following rTMS. rTMS was given in the form of theta burst stimulation (TBS) using the inhibitory protocol "cTBS" (total of 300 pulses in 50-Hz bursts given every 5Hz). DYT1 gene carriers with dystonia and subjects with torticollis had a significantly prolonged response to rTMS in comparison with healthy subjects. In contrast, DYT1 gene carriers without dystonia had no significant response to rTMS. These data demonstrate an excessive response to an experimental "plasticity probing protocol" in subjects with dystonia, but a lack of response in genetically susceptible individuals who have not developed dystonia. These preliminary data suggest that the propensity to undergo plastic change may affect the development of symptoms in genetically susceptible individuals and that this may be an important mechanism in the pathogenesis of primary dystonia in general.     

A heterozygous effect for PINK1 mutations in Parkinson's disease?

OBJECTIVE: To investigate the significance of PINK1 mutations in sporadic Parkinson's disease (PD). METHODS: We determined the frequency of PINK1 mutations by direct sequencing in a large series of PD patients with apparently sporadic disease (n = 768). RESULTS: Twelve heterozygous mutations were identified, nine in PD patients and three in control subjects. INTERPRETATION: Given the difficulty in interpreting the pathogenic significance of the heterozygous mutations that have already been reported in parkin and DJ-1, we first determined the frequency of heterozygous PINK1 mutations in the general population by sequencing a large number of control subjects (n = 768), then subsequently assessed their functional significance by examining their effects on stress-induced alterations to the mitochondrial membrane potential (DeltaPsim). We demonstrate an enrichment of heterozygous mutations in sporadic PD patients compared with matched control subjects (1.2% in PD vs 0.4% in control subjects). Furthermore, we show that they adversely affect DeltaPsim in a similar way to the familial G309D mutation. Although it remains difficult to conclusively demonstrate the pathogenicity of heterozygous mutations, the results of this study and the previously reported subclinical nigrostriatal dysfunction in carriers of heterozygous PINK1 mutations suggest the possibility that these heterozygous mutations are a significant risk factor in the development of later onset PD.