Clinical Aspects of the Differential Diagnosis of Parkinson’s Disease and Parkinsonism

Parkinsonism is a clinical syndrome presenting with bradykinesia, tremor, rigidity, and postural instability. Nonmotor symptoms have recently been included in the parkinsonian syndrome, which was traditionally associated with motor symptoms only. Various pathologically distinct and unrelated diseases have the same clinical manifestations as parkinsonism or parkinsonian syndrome. The etiologies of parkinsonism are classified as neurodegenerative diseases related to the accumulation of toxic protein molecules or diseases that are not neurodegenerative. The former class includes Parkinson’s disease (PD), multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Over the past decade, clinical diagnostic criteria have been validated and updated to improve the accuracy of diagnosing these diseases. The latter class of disorders unrelated to neurodegenerative diseases are classified as secondary parkinsonism, and include drug-induced parkinsonism (DIP), vascular parkinsonism, and idiopathic normal-pressure hydrocephalus (iNPH). DIP and iNPH are regarded as reversible and treatable forms of parkinsonism. However, studies have suggested that the absence of protein accumulation in the nervous system as well as managing the underlying causes do not guarantee recovery. Here we review the differential diagnosis of PD and parkinsonism, mainly focusing on the clinical aspects. In addition, we describe recent updates to the clinical criteria of various disorders sharing clinical symptoms with parkinsonism.

Comparison of RCF Scoring System to Clinical Decision for the Rey Complex Figure Using Machine-Learning Algorithm

Background@#and Purpose: Interpreting the Rey complex figure (RCF) requires a standard RCF scoring system and clinical decision by clinicians. The interpretation of RCF using clinical decision by clinicians might not be accurate in the diagnosing of mild cognitive impairment (MCI) or dementia patients in comparison with the RCF scoring system. For this reason, a machine-learning algorithm was used to demonstrate that scoring RCF using clinical decision is not as accurate as of the RCF scoring system in predicting MCI or mild dementia patients from normal subjects. @*Methods@#The RCF dataset consisted of 2,232 subjects with formal neuropsychological assessments. The RCF dataset was classified into 2 datasets. The first dataset was to compare normal vs. abnormal and the second dataset was to compare normal vs. MCI vs. mild dementia. Models were trained using a convolutional neural network for machine learning.Receiver operating characteristic curves were used to compare the sensitivity, specificity, and area under the curve (AUC) of models. @*Results@#The trained model's accuracy for predicting cognitive states was 96% with the first dataset (normal vs. abnormal) and 88% with the second dataset (normal vs. MCI vs. mild dementia). The model had a sensitivity of 85% for detecting abnormal with an AUC of 0.847 with the first dataset. It had a sensitivity of 78% for detecting MCI or mild dementia with an AUC of 0.778 with the second dataset. @*Conclusions@#Based on this study, the RCF scoring system has the potential to present more accurate criteria than the clinical decision for distinguishing cognitive impairment among patients.

Coping with Dementia in the Middle of the COVID-19 Pandemic

Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs.

Reliability and Validity of a Short Form of the Korean Dementia Screening Questionnaire-Cognition

Cerebrospinal Fluid Levels of β-Amyloid 40 and β-Amyloid 42 are Proportionately Decreased in Amyloid Positron-Emission Tomography Negative Idiopathic Normal-Pressure Hydrocephalus Patients

BACKGROUND AND PURPOSE: Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) could be misleading in idiopathic normal-pressure hydrocephalus (iNPH). We therefore investigated the CSF biomarkers in 18F-florbetaben amyloid-negative positron-emission tomography (PET) [amyloid PET(−)] iNPH, amyloid-positive PET [amyloid PET(+)] AD, and cognitively normal (CN) subjects. METHODS: Ten amyloid PET(+) AD patients (56.7±5.6 years old, mean±standard deviation), 10 amyloid PET(−) iNPH patients (72.8±4.5 years old), and 8 CN subjects (61.2±6.5 years old) were included. We measured the levels of β-amyloid (Aβ)40, Aβ42, total tau (t-tau) protein, and phosphorylated tau (p-tau) protein in the CSF using enzyme-linked immunosorbent assays. RESULTS: The level of Aβ42 and the Aβ42/Aβ40 ratio in the CSF were significantly lower in AD than in iNPH or CN subjects. The Aβ40 level did not differ significantly between AD and iNPH (p=1.000), but it did between AD and CN subjects (p=0.032). The levels of both t-tau and p-tau were higher in AD than in iNPH or CN subjects. The levels of Aβ42, Aβ40, t-tau, and p-tau were lower in iNPH than in CN subjects, but there was no significant difference after controlling for age. CONCLUSIONS: Our results suggest that the mechanism underlying low CSF Aβ levels differs between amyloid PET(−) iNPH and amyloid PET(+) AD subjects. The lower levels of all CSF biomarkers in iNPH patients might be due to reduced clearances from extracellular fluid and decreased brain metabolism of the periventricular zone in iNPH resulting from glymphatic dysfunction.

A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203

A Comparative Evaluation of the KDSQ-C, AD8, and SMCQ as a Cognitive Screening Test to Be Used in National Medical Check-ups in Korea

BACKGROUND: Korea has a periodic general health check-up program that uses the Korean Dementia Screening Questionnaire-Cognition (KDSQ-C) as a cognitive dysfunction screening tool. The Alzheimer Disease 8 (AD8) and Subjective Memory Complaints Questionnaire (SMCQ) are also used in clinical practice. We compared the diagnostic ability of these screening questionnaires for cognitive impairment when completed by participants and their caregivers. Hence, we aimed to evaluate whether the SMCQ or AD8 is superior to the KDSQ-C and can be used as its replacement. METHODS: A total of 420 participants over 65 years and their informants were recruited from 11 hospitals for this study. The patients were grouped into normal cognition, mild cognitive impairment, and dementia subgroups. The KDSQ-C, AD8, and SMCQ were completed separately by participants and their informants. RESULTS: A receiver operating characteristic analysis of questionnaire scores completed by participants showed that the areas under the curve (AUCs) for the KDSQ-C, AD8, and SMCQ for diagnosing dementia were 0.75, 0.8, and 0.73, respectively. Regarding informant-completed questionnaires, the AD8 (AUC of 0.93), KDSQ-C (AUC of 0.92), and SMCQ (AUC of 0.92) showed good discriminability for dementia, with no differences in discriminability between the questionnaires. CONCLUSION: When an informant-report is possible, we recommend that the KDSQ-C continues to be used in national medical check-ups as its discriminability for dementia is not different from that of the AD8 or SMCQ. Moreover, consistent data collection using the same questionnaire is important. When an informant is not available, either the KDSQ-C or AD8 may be used. However, in the cases of patient-reports, discriminability is lower than that for informant-completed questionnaires.

Age-Specific Cutoff Scores on a T1-Weighted Axial Medial Temporal-Lobe Atrophy Visual Rating Scale in Alzheimer's Disease Using Clinical Research Center for Dementia of South Korea Data

BACKGROUND AND PURPOSE: Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to apply in routine clinical practice. However, one of the limitations in visual assessments of MTA is the lack of widely accepted age-adjusted norms and cutoff scores for MTA for a diagnosis of Alzheimer's disease (AD). This study aimed to determine the optimal cutoff score on a T1-weighted axial MTA Visual Rating Scale (VRS) for differentiating patients with AD from cognitively normal elderly people. METHODS: The 3,430 recruited subjects comprising 1,427 with no cognitive impairment (NC) and 2003 AD patients were divided into age ranges of 50–59, 60–69, 70–79, and 80–89 years. Of these, 446 participants (218 in the NC group and 228 in the AD group) were chosen by random sampling for inclusion in this study. Each decade age group included 57 individuals, with the exception of 47 subjects being included in the 80- to 89-year NC group. The scores on the T1-weighted axial MTA VRS were graded by two neurologists. The cutoff values were evaluated from the area under the receiver operating characteristic curve. RESULTS: The optimal axial MTA VRS cutoff score from discriminating AD from NC increased with age: it was ≥as ≥1, ≥2, and ≥3 in subjects aged 50–59, 60–69, 70–79, and 80–89 years, respectively (all p < 0.001). CONCLUSIONS: These results show that the optimal cutoff score on the axial MTA VRS for diagnosing of AD differed according to the decade age group. This information could be of practical usefulness in the clinical setting.

Artificial Neural Network: Understanding the Basic Concepts without Mathematics

Machine learning is where a machine (i.e., computer) determines for itself how input data is processed and predicts outcomes when provided with new data. An artificial neural network is a machine learning algorithm based on the concept of a human neuron. The purpose of this review is to explain the fundamental concepts of artificial neural networks.

A Consensus in Korea Regarding a Protocol to Reduce Preanalytical Sources of Variability in the Measurement of the Cerebrospinal Fluid Biomarkers of Alzheimer's Disease

Cerebrospinal fluid (CSF) can provide vital informative about pathological processes occurring in the brain. In particular, the CSF concentrations of Abeta42, tTau, and pTau181 are useful for the early diagnosis of Alzheimer's disease (AD). However, many studies have demonstrated that confounding factors related to the preanalytical processing of CSF can seriously influence measurements of these AD biomarkers. It is therefore important to develop a standardized protocol for the acquisition and handling of CSF, particularly with regard to the types of tube used for collection and storage, the proper aliquot volume, blood contamination, and the number of tube transfers and freeze-thaw cycles, because these aspects of the procedure have been shown to affect AD biomarker measurements. A survey of the impact of several individual preanalytical procedures on the measurement of AD biomarkers in CSF was conducted for this review article, and the implications of the differences among them are discussed. Furthermore, following a review of the procedures used in Korean and international biomarker laboratories, a consensus was reached among a cooperative Korean multicenter research group regarding a standardized protocol for the analysis of AD biomarkers in CSF. All efforts were made to be stringent regarding the controversial issues associated with this protocol, thus minimizing the confounding influence of various factors on current investigations using established AD biomarkers and on future studies using novel biomarkers of AD and other neurodegenerative disorders.

A Voxel Based Morphometric Analysis of Longitudinal Cortical Gray Matter Changes in Progranulin Mutation Carriers At-Risk for Frontotemporal Dementia: Preliminary Study

BACKGROUND AND PURPOSE: One of the most common genetic causes of frontotemporal dementia (FTD) is mutation in the progranulin (PGRN) gene. The aim of this study is to assess the early effects of the PGRN mutations on brain volumes by longitudinal voxel based morphometric (VBM) evaluation in asymptomatic mutation carriers. METHODS: We recruited 17 asymptomatic members of families with FTD caused by PGRN mutations; 7 mutation carriers (51.0+/-11.6 yr) and 10 non-carriers (55.2+/-6.0 yr, p=0.404). The MRI follow-up intervals of carriers and non-carriers were 788.6+/-103.8 and 922.0+/-225.1 days (p=0.124) respectively. We performed cross-sectional and longitudinal VBM analysis on both groups. RESULTS: At baseline, the carriers had lower white matter (WM) volumes in left frontal regions (p<0.001, uncorrected), but had no gray matter (GM) volume reduction. The carrier's global GM (p=0.924) and WM volume (p=0.364) reduction rate were not different from the non-carrier's. However, statistical parametric mapping T-maps showed differentially increased GM volume reductions in the bilateral parietal areas of carriers (p<0.001, uncorrected). CONCLUSIONS: The findings from this study to examine WM and GM cross-sectional and longitudinal changes in PGRN mutation carriers suggest that WM atrophic changes could precede both GM changes and symptom onset in FTD. Asymptomatic PGRN mutation carriers have measurably higher rates of regional GM atrophy than non-carriers even in the pre-dementia stages.

Efficacy of the Phosphorylated tau 181 in Differential Diagnosis of the Alzheimer's Disease: A Systematic Review and Meta-Analysis

BACKGROUND: The purpose of this study was to evaluate the value of phosphorylated tau with epitopes threonine 181(p-tau181) in cerebrospinal fluid (CSF) for the differential diagnosis of Alzheimer's disease typed dementia from other type of dementia. METHODS: A systematic literature search was performed to identify studies on p-tau181. Two evaluators independently evaluated the quality of the ten studies using the Scottish Intercollegiate Guidelines Network (SIGN) tool. The literature review covered from October 27, 1946 to October 22, 2013, and eight domestic databases including KoreaMed and international databases including Ovid-MEDLINE, EMBASE, and Cochrane Library were used. Tau concentrations were compared to healthy controls and to subjects with Alzheimer's disease (AD) using random effect meta-analysis. Outcome measures were Cohen's delta, sensitivity and specificity. RESULTS: Finally, 8 studies (8 diagnostic evaluation studies) were identified to evaluate CSF p-tau181. The effectiveness of this test was evaluated based on diagnostic accuracy. The diagnostic accuracy for identifying AD by ELISA was high which revealed pooled sensitivity as 0.843 (95% CI 0.818-0.867), pooled specificity as 0.799(95% CI 0.768-0.828) and summary receiver operating characteristic area under the curve 0.9082+/-0.0236. CONCLUSIONS: CSF p-tau181 concentrations in other type of dementia are intermediate between controls and AD patients. Overlap between both controls and AD patients results in insufficient diagnostic accuracy, and the development of more specific biomarkers for these disorders is needed.

Argyria Accompanied by Normal Pressure Hydrocephalus

A 54-year-old man ingesting silver solution over 4 years presented with cognitive impairment and progressive gait disturbance. He had diffuse gray pigmentation on his face and fingertips, suggesting argyria. Brain magnetic resonance imaging (MRI) revealed hydrocephalus and high concentration of silver ion is in blood. This is the first case occuring hydrocephalus associated with the neurotoxicity of silver.

Clinical practice guideline for dementia by Clinical Research Center for Dementia of South Korea

The Clinical Research Center for Dementia of South Korea (CREDOS), a nation-wide clinical dementia research group, has prepared clinical practice guidelines (CPG) for dementia tailored to the Korean population. In this article, a summary of the CREDOS CPG is presented with the Korean and English version of full report included in the appendix. The CREDOS CPG in intended not only for psychiatrists and neurologists, but also internists, family physicians, and other primary care physicians involved in the prevention and early diagnosis of dementia. While our CPG for dementia mainly covers Alzheimer's disease (AD) and vascular dementia (VaD), it also includes mild cognitive impairment (MCI) and vascular MCI, which are currently known to be the preclinical stages of AD or VaD, respectively, with emphasis placed on early diagnosis. The CREDOS CPG aims to achieve the following goals by developing CPG for dementia: to establish evidence-based, objective and clear clinical standards for dementia; to improve the clinical decision-making process for patients with dementia; to provide scientific and systematic scales to aid in the work of dementia specialists; to suggest comprehensive and systematic healthcare services tailored to each dementia subtype. The CREDOS CPG focuses on diagnosis and evaluation of clinical practice available domestically, and provides useful concepts of dementia. Its emphasis is on etiologies and epidemiology, diagnostic criteria and evaluation, neuropsychological tests, behavioral and psychological symptoms, the activities of daily living, laboratory tests, and brain imaging.

Isolated Spinal Cord Neurosarcoidosis Diagnosed by Cord Biopsy and Thalidomide Trial

We report a case of 54-yr-old woman who presented with 4-extremities weakness and sensory changes, followed by cervical spinal cord lesion in magnetic resonance imaging. Based on the suspicion of spinal tumor, spinal cord biopsy was performed, and the histology revealed multinucleated giant cells, lymphocytes and aggregated histiocytes within granulomatous inflammation, consistent with non-caseating granuloma seen in sarcoidosis. The patient was treated with corticosteroid, immunosuppressant and thalidomide for years. Our case indicates that diagnosis of spinal cord sarcoidosis is challenging and may require histological examination, and high-dose corticosteroid and immunosuppressant will be a good choice in the treatment of spinal cord sarcoidosis, and the thalidomide has to be debated in the spinal cord sarcoidosis.

Caudate Volume Change in Transient Global Amnesia Patients; Voxel-Based Morphometric Study

BACKGROUND: Transient global amnesia (TGA) is characterized by a severe disturbance of memory, lasting less than a day, and complete resolution. However, some authors have suggested the occurrence of permanent memory impairment in such cases. In this study, we investigated whether the gray-matter structure suffers degeneration in TGA, based on the assumption that TGA attacks appear to be related to underlying permanent pathology. METHODS: T1-weighted magnetic resonance imaging data for 20 TGA and 55 normal subjects were analyzed. The gray-matter volume was measured using voxel-based morphometry. The subjects also completed the Seoul Neuropsychological Screening Battery (SNSB). RESULTS: The gray-matter volume was reduced in the left superior frontal gyrus, right precentral gyrus, right superior frontal gyrus, left caudate nucleus, left precentral gyrus, left post central gyrus, and both putamens. The SNSB revealed the presence of selective neuropsychological dysfunctions after clinical recovery. Most of the cases exhibited attention deficit, and difficulties in copying of the Rey-Osterrieth Complex Figure, and in the Seoul verbal learning test. CONCLUSIONS: Left caudate nucleus atrophy could explain the attention deficit and memory impairment experienced in these TGA patients. Many patients with TGA have neuropsychological dysfunctions even after they appear to be clinically improved.

An easy and secure pancreaticogastrostomy after pancreaticoduodenectomy: transpancreatic suture with a buttress method through an anterior gastrotomy / 대한외과학회지

PURPOSE: The aim of this report was to describe a new reconstructive technique of pancreaticogastrostomy and to also discuss this procedure's effectiveness for reducing the incidence of postoperative complications. METHODS: We retrospectively analyzed early surgical outcomes in 21 consecutive patients who underwent this novel pancreaticogastrostomy after pancreaticoduodenectomy. Pancreaticogastrostomy was completed with 2 transpancreatic sutures with buttresses on both the upper and lower edges of the implanted pancreas through the retracted anterior gastrotomy. RESULTS: Operative mortality was zero and morbidity was 23.8%. A significant pancreatic fistula occurred in 1 patient (4.7%; grade B). CONCLUSION: This technique is very easy to perform, less traumatic to the pancreatic stump, can be performed through a mini-laparotomy due to good vision and straight sutures, and it is secure owing to anchoring of the invaginated pancreatic stump to the stomach's posterior wall with buttresses. The results of this pilot study indicate that the technique may provide a favorable outcome and could be an alternative method of pancreatoenteric anastomosis. However, to determine its superiority over the conventional procedures, this operative technique should be evaluated more comprehensively in a larger series.

An easy and secure pancreaticogastrostomy after pancreaticoduodenectomy: transpancreatic suture with a buttress method through an anterior gastrotomy / 대한외과학회지

PURPOSE: The aim of this report was to describe a new reconstructive technique of pancreaticogastrostomy and to also discuss this procedure's effectiveness for reducing the incidence of postoperative complications. METHODS: We retrospectively analyzed early surgical outcomes in 21 consecutive patients who underwent this novel pancreaticogastrostomy after pancreaticoduodenectomy. Pancreaticogastrostomy was completed with 2 transpancreatic sutures with buttresses on both the upper and lower edges of the implanted pancreas through the retracted anterior gastrotomy. RESULTS: Operative mortality was zero and morbidity was 23.8%. A significant pancreatic fistula occurred in 1 patient (4.7%; grade B). CONCLUSION: This technique is very easy to perform, less traumatic to the pancreatic stump, can be performed through a mini-laparotomy due to good vision and straight sutures, and it is secure owing to anchoring of the invaginated pancreatic stump to the stomach's posterior wall with buttresses. The results of this pilot study indicate that the technique may provide a favorable outcome and could be an alternative method of pancreatoenteric anastomosis. However, to determine its superiority over the conventional procedures, this operative technique should be evaluated more comprehensively in a larger series.

Clinical Characteristics of a Nationwide Hospital-based Registry of Mild-to-Moderate Alzheimer's Disease Patients in Korea: A CREDOS (Clinical Research Center for Dementia of South Korea) Study

With rapid population aging, the socioeconomic burden caused by dementia care is snowballing. Although a few community-based studies of Alzheimer's disease (AD) have been performed in Korea, there has never been a nationwide hospital-based study thereof. We aimed to identify the demographics and clinical characteristics of mild-to-moderate AD patients from the Clinical Research Center for Dementia of Korea (CREDOS) registry. A total of 1,786 patients were consecutively included from September 2005 to June 2010. Each patient underwent comprehensive neurological examination, interview for caregivers, laboratory investigations, neuropsychological tests, and brain MRI. The mean age was 74.0 yr and the female percentage 67.0%. The mean period of education was 7.1 yr and the frequency of early-onset AD (< 65 yr old) was 18.8%. Among the vascular risk factors, hypertension (48.9%) and diabetes mellitus (22.3%) were the most frequent. The mean score of the Korean version of Mini-Mental State Examination (K-MMSE) was 19.2 and the mean sum of box scores of Clinical Dementia Rating (CDR-SB) 5.1. Based on the well-structured, nationwide, and hospital-based registry, this study provides the unique clinical characteristics of AD and emphasizes the importance of vascular factors in AD in Korea.

Expanded Criteria for Living Donor Liver Transplantation in Patients with Advanced Hepatocellular Carcinoma

PURPOSE: The purpose of this study was to evaluate the possibility of expanding the indication for living donor liver transplantation (LDLT) for treatment of hepatocellular carcinoma (HCC), beyond the Milan criteria without compromising patient survival. METHODS: This was a retrospective study of 5patients (36.4%) that had undergone LDLT, beyond the Milan criteria, among 143 patients with HCC. The study was conducted in patients treated by the Department of Surgery, Catholic University of Korea from Oct 2000 to May 2008. We evaluated the survival curve, prognostic factors for survival and compared survival between our new criteria and Milan criteria. RESULTS: The 5 year patient survival and disease free survival rate in patients treated with LDLT beyond the Milan criteria were 50.2% and 61.9%, respectively. The prognostic factors affecting disease free survival and patient survival included serum AFP level, tumor size, vascular invasion, and tumor cell differentiation on univariate analysis. In multivariate analysis, AFP (200 ng/mL), tumor size (7 cm) and vascular invasion had significant influence on survival and disease free survival. According to our new criteria (size <7 cm, AFP <200 ng/ mL), 88.1% of our patients were included compare to the 63.6% that would have been if limited to the Milan criteria. With both factors met, the survival was comparable to the survival of Milan criteria (63.7% on our criteria and 78.2% on Milan criteria at 5 years) (P =0.103). CONCLUSION: A tumor size <7 cm and an AFP < 200 ng/mL appear to be useful cut-off values, beyond that criteria required by Milan. An analysis according to our criteria showed an acceptable survival outcome. Further verification of these findings by a large volume or prospective study is required for widespread adoption of our new criteria.