Loss of cell wall integrity genes cpxA and mrcB causes flocculation in Escherichia coli.

Flocculation has been recognized for hundreds of years as an important phenomenon in brewing and wastewater treatment. However, the underlying molecular mechanisms remain elusive. The lack of a distinct phenotype to differentiate between slow-growing mutants and floc-forming mutants prevents the isolation of floc-related gene by conventional mutant screening. To overcome this, we performed a two-step Escherichia coli mutant screen. The initial screen of E. coli for mutants conferring floc production during high salt treatment yielded a mutant containing point mutations in 61 genes. The following screen of the corresponding single-gene mutants identified two genes, mrcB, encoding a peptidoglycan-synthesizing enzyme and cpxA, encoding a histidine kinase of a two-component signal transduction system that contributed to salt tolerance and flocculation prevention. Both single mutants formed flocs during high salt shock, these flocs contained cytosolic proteins. ΔcpxA exhibited decreased growth with increasing floc production and addition of magnesium to ΔcpxA suppressed floc production effectively. In contrast, the growth of ΔmrcB was inconsistent under high salt conditions. In both strains, flocculation was accompanied by the release of membrane vesicles containing inner and outer membrane proteins. Of 25 histidine kinase mutants tested, ΔcpxA produced the highest amount of proteins in floc. Expression of cpxP was up-regulated by high salt in ΔcpxA, suggesting that high salinity and activation of CpxR might promote floc formation. The finding that ΔmrcB or ΔcpxA conferred floc production indicates that cell envelope stress triggered by unfavorable environmental conditions cause the initiation of flocculation in E. coli.

Sex differences in reference values of hip acetabular measurements using computed tomography in Japanese adults and the effect of aging on the measurement parameters.

BACKGROUND: It is very important to understand the acetabular morphology of the normal hip joint to assist in diagnosis and surgical planning of hip disorders. The purpose of the present study was to obtain gender-based reference values for the acetabular measurements of a normal hip using computed tomography data and investigate the effect of aging on the measurement values. METHODS: We measured acetabular parameters (center-edge angle, Sharp angle, vertical center anterior angle, acetabular anteversion) on computed tomography corrected for changing the obliquity, rotation, and tilt of the pelvis. We performed measurements in 245 patients (490 joints; 120 men [240 joints] and 125 women [250 joints]). The mean age was 64.7 ± 14.3 (31-88) years for men and 63.2 ± 15.2 (30-88) years for women. RESULTS: In men and women, the mean center-edge angle was 31.8° ± 6.4° and 30.6° ± 6.5°, the mean Sharp angle was 38.6° ± 3.2° and 40.6° ± 3.8°, the mean vertical center anterior angle was 44.3° ± 7.9° and 40.0° ± 8.5°, and the mean acetabular anteversion angle was 14.3° ± 5.2° and 18.8° ± 5.4°, respectively. All differences were statistically significant. The center-edge angle increased with age in women; however, such an effect was not observed in men. The other measurements showed a similar trend, such as larger vertical center anterior angle and smaller Sharp and acetabular anteversion angles, with aging in both men and women. CONCLUSIONS: We used computed tomography data to quantitatively assess the coverage and shape of the acetabulum in adult Japanese subjects and obtain the estimated reference ranges by gender. The results also proved that the measurements changed with aging in both sexes. These facts must be taken into account during the diagnosis of hip disease and planning of surgery.

Identification and visualization of oxidized lipids in atherosclerotic plaques by microscopic imaging mass spectrometry-based metabolomics.

BACKGROUND AND AIMS: Dysregulated lipid metabolism has emerged as one of the major risk factors of atherosclerosis. Presently, there is a consensus that oxidized LDL (oxLDL) promotes development of atherosclerosis and downstream chronic inflammatory responses. Due to the dynamic metabolic disposition of lipoprotein, conventional approach to purify bioactive lipids for subsequent comprehensive analysis has proven to be inadequate for elucidation of the oxidized lipids species accountable for pathophysiology of atherosclerotic lesions. Herein, we aimed to utilize a novel mass microscopic imaging technology, coupled with mass spectrometry (MS) to characterize oxidized lipids in atherosclerotic lesions. METHODS: We attempted to use MALDI-TOF-MS and iMScope to identify selected oxidized lipid targets and visualize their respective localizations in study models of atherosclerosis. RESULTS: Based on the MS analysis, detection of 7-K under positive ionization through product ion peak at m/z 383 [M + H-H2O] indicated the distinctive presence of targeted lipid within Cu2+-oxLDL and Cu2+-oxLDL loaded macrophage-like J774A.1 cells, along with other cholesterol oxidation products. Moreover, the application of two-dimensional iMScope has successfully visualized the localization of lipids in aortic atherosclerotic plaques of the Watanabe heritable hyperlipidemic (WHHL) rabbit. Distinctive lipid distribution profiles were observed in atherosclerotic lesions of different sizes, especially the localizations of lysoPCs in atherosclerotic plaques. CONCLUSIONS: Taken together, we believe that both MALDI-TOF-MS and iMScope metabolomics technology may offer a novel proposition for future pathophysiological studies of lipid metabolism in atherosclerosis.

Current Ventilator and Oxygen Management during General Anesthesia: A Multicenter, Cross-sectional Observational Study.

BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

Reduction of Spermidine Content Resulting from Inactivation of Two Arginine Decarboxylases Increases Biofilm Formation in Synechocystis sp. Strain PCC 6803.

The phototropic bacterium Synechocystis sp. strain PCC 6803 is able to adapt its morphology in order to survive in a wide range of harsh environments. Under conditions of high salinity, planktonic cells formed cell aggregates in culture. Further observations using crystal violet staining, confocal laser scanning microscopy, and field emission-scanning electron microscopy confirmed that these aggregates were Synechocystis biofilms. Polyamines have been implicated in playing a role in biofilm formation, and during salt stress the content of spermidine, the major polyamine in Synechocystis, was reduced. Two putative arginine decarboxylases, Adc1 and Adc2, in Synechocystis were heterologously expressed in Escherichia coli and purified. Adc2 had high arginine decarboxylase activity, whereas Adc1 was much less active. Disruption of the adc genes in Synechocystis resulted in decreased spermidine content and formation of biofilms even under nonstress conditions. Based on the characterization of the adc mutants, Adc2 was the major arginine decarboxylase whose activity led to inhibition of biofilm formation, and Adc1 contributed only minimally to the process of polyamine synthesis. Taken together, in Synechocystis the shift from planktonic lifestyle to biofilm formation was correlated with a decrease in intracellular polyamine content, which is the inverse relationship of what was previously reported in heterotroph bacteria.IMPORTANCE There are many reports concerning biofilm formation in heterotrophic bacteria. In contrast, studies on biofilm formation in cyanobacteria are scarce. Here, we report on the induction of biofilm formation by salt stress in the model phototrophic bacterium Synechocystis sp. strain PCC 6803. Two arginine decarboxylases (Adc1 and Adc2) possess function in the polyamine synthesis pathway. Inactivation of the adc1 and adc2 genes leads to biofilm formation even in the absence of salt. The shift from planktonic culture to biofilm formation is regulated by a decrease in spermidine content in Synechocystis This negative correlation between biofilm formation and polyamine content, which is the opposite of the relationship reported in other bacteria, is important not only in autotrophic but also in heterotrophic bacteria.

Mutants of ß2-glycoprotein I: Their features and potent applications.

ß2-Glycoprotein I (ß2GPI) is a highly-glycosylated plasma protein composed of five homologous domains which regulates coagulation, fibrinolysis, and/or angiogenesis by interacting to negatively charged hydrophobic molecules and/or with plasminogen and its metabolites. The present study focused on structural and functional characterization of ß2GPI's domain I (DI) and V (DV). Through N-terminal amino acid sequencing, a novel plasmin-cleaved site at K287C288 was identified in DV. We further modified the intact DV by altering two amino acids at specific proteolytic cleavage sites to generate three stable DV mutants: DV(PP), (PE), and (AA). Results of both SDS-PAGE and MALDI-TOF-MS showed that all three DV mutants were more stable than the intact DV, and DV(PE) was predominantly resistant to proteolysis. Competitive ELISA assessed affinities of intact ß2GPI and those mutants to cardiolipin. In culture system, all DV and DI mutants potently inhibited HUVEC's proliferation by 18-30% as compared to control. Only DI and nicked ß2GPI showed significant inhibition in HUVEC's tube formation. Moreover, DV(PE)-coated affinity columns demonstrated its binding property towards anionic lipids and could substantially isolate anionic DOPS from zwitterionic DOPC as a purification model. In summary, the proteolytic resistant and unhindered phospholipid (PL) binding properties of DV(PE) have made it an appealing element for subsequent prospective studies. Future in-depth characterization and optimized applications of cleavage-resistant DV(PE) would complement its full capacity as a novel clinical modality in the field of vascular imaging and/or lipidomics studies.

Continuous paravertebral block using a thoracoscopic catheter-insertion technique for postoperative pain after thoracotomy: a retrospective case-control study.

BACKGROUND: Thoracic epidural analgesia (EDA) is the gold standard for pain control after thoracotomy. However, because of its severe side effects, it is contraindicated in patients taking anticoagulant or antiplatelet drugs. In addition, some patients' anatomy can make epidural catheter insertion challenging. We therefore investigated the safety and efficacy of paravertebral block (PVB) using a thoracoscopic insertion technique, which avoids damage to the parietal pleura, for postoperative pain after thoracotomy. METHODS: Patients who underwent thoracotomy with thoracic PVB in our hospital between March 2013 and March 2014 were examined retrospectively. Prior to creating the thoracotomy incision, a catheter for PVB was inserted percutaneously into the paravertebral space under thoracoscopic guidance. A matched-pair control group was selected at a 1:2 ratio from patients who underwent thoracotomy with thoracic EDA in our hospital from April 2011 to February 2013. Pain control and side effects were compared between groups and the results statistically analyzed. RESULTS: Thoracic PVB was performed in 56 patients during this period, and 112 patients were selected as matched controls. Numeric Rating Scale scores on postoperative day 2 did not differ significantly between the PVB group (3.25 ± 1.80) and the EDA group (3.56 ± 2.05) (p = 0.334). In terms of side effects, urinary retention occurred less frequently in thoracic PVB patients (p = 0.03). CONCLUSION: Under the conditions of the present study, continuous thoracic PVB was at least as effective as epidural analgesia for postoperative pain control after thoracotomy with lung resection.

[Thoracic Paravertebral Block in Patients Ineligible for Epidural Block].

We retrospectively assessed the effectiveness and the safety of thoracic paravertebral block(PVB) in patients ineligible for epidural block (EP). Eleven PVB patients and 33 EP patients were enrolled. Postoperative pain was evaluated using a numerical rating scale (NRS). The mean NRS ± standard deviation at rest 24 and 48 hours after surgery were 1.36 ± 1.63 and 0.55 ± 1.03 in the PVB group and 1.07 ± 1.47 and 1.38 ± 1.31 in the EP group, respectively. There were no statistically significant differences in the NRS scores. Approximately 10% of the EP patients had complications such as hypotension, nausea and vomiting, or urinary retention. On the other hand, there were no adverse events in the PVB group. PVB can provide pain relief comparable to EP with a better side-effect profile. There were no technical complications associated with PVB. Thoracic PVB is an effective and safe method of postoperative analgesia for patients undergoing thoracic surgery with ineligibilities for EP.

The Function of ß2-glycoprotein I in Angiogenesis and Its in Vivo Distribution in Tumor Xenografts.

Intact ß2-glycoprotein I (iß2GPI) is a glycoprotein that regulates coagulation and fibrinolysis. Nicked ß2GPI (nß2GPI) possesses an angiogenic property at a relatively low concentration, and an antiangiogenic property at a high concentration. Here we investigated the functions of ßi 2GPI and nß2GPI in vascular endothelial growth factor (VEGF)-A-induced endothelial cell proliferation and tube formation. We used noninvasive PET imaging to analyze the ｉｎ　ｖｉｖｏ distribution of intravenously injected ß2GPI variants in tumor lesions in mice. iß2GPI was incubated with plasmin to obtain nß2GPI, and its N-terminal sequence was analyzed. nß2GPI had at least one other cleavage site upstream of the ß2GPI's domain V, whereas the former plasmin-cleavage site locates between K317 and T318. Both of intact and nicked ß2GPI significantly inhibited the VEGF-A-induced cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs). PET imaging visualized considerably distributed intensities of all tested ß2GPI variants in tumor lesions of pancreatic tumor cell-xenografts. These results indicate that ß2GPI may be physiologically and pathophysiologically important in the regulation of not only coagulation and fibrinolysis, but also angiogenesis.

A cell-free translocation system using extracts of cultured insect cells to yield functional membrane proteins.

Cell-free protein synthesis is a powerful method to explore the structure and function of membrane proteins and to analyze the targeting and translocation of proteins across the ER membrane. Developing a cell-free system based on cultured cells for the synthesis of membrane proteins could provide a highly reproducible alternative to the use of tissues from living animals. We isolated Sf21 microsomes from cultured insect cells by a simplified isolation procedure and evaluated the performance of the translocation system in combination with a cell-free translation system originating from the same source. The isolated microsomes contained the basic translocation machinery for polytopic membrane proteins including SRP-dependent targeting components, translocation channel (translocon)-dependent translocation, and the apparatus for signal peptide cleavage and N-linked glycosylation. A transporter protein synthesized with the cell-free system could be functionally reconstituted into a lipid bilayer. In addition, single and double labeling with non-natural amino acids could be achieved at both the lumen side and the cytosolic side in this system. Moreover, tail-anchored proteins, which are post-translationally integrated by the guided entry of tail-anchored proteins (GET) machinery, were inserted correctly into the microsomes. These results showed that the newly developed cell-free translocation system derived from cultured insect cells is a practical tool for the biogenesis of properly folded polytopic membrane proteins as well as tail-anchored proteins.

Relative contribution of insulin secretion and sensitivity at different stages of glucose tolerance: non-obese versus obese Japanese subjects.

OBJECTIVE: We examined the relative contribution of insulin secretion and insulin sensitivity at different stages of glucose tolerance in non-obese and obese Japanese subjects. METHODS: A total of 641 subjects who underwent 75-g glucose tolerance testing were divided into two groups: 436 non-obese subjects (body mass index: BMI <25) and 205 obese subjects (BMI ≥25). The subjects were further divided into four groups: those with normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes. We compared insulin secretion and sensitivity indices, such as the insulinogenic index (IGI), homeostatic model insulin resistance (HOMA-IR), homeostatic model assessment of ß-cell (HOMA-ß) and insulin sensitivity index (ISI). RESULTS: In a univariate analysis, the obese subjects had higher levels of HOMA-IR, HOMA-ß and IGI associated with lower ISI values in comparison with that observed in the non-obese subjects at different stages of glucose tolerance. A multiple logistic regression analysis showed that the HOMA-IR was a significant independent factor between the non-obese and obese subjects; the odds ratio (OR) (95% confidential interval: CI) was 3.78 (2.04-7.01; p<0.01) in the NGT group, 4.91 (2.06-11.72; p<0.01) in the IGT group and 2.02 (1.22-3.34; p<0.01) in the diabetes group. Although a similar trend was also observed in the IFG group (OR=15.83), the difference did not reach a level of statistical significance (p=0.066). CONCLUSION: These data suggest that obese subjects are characterized by increased insulin resistance rather than reduced insulin secretion at all stages of glucose tolerance. Therefore, non-obese subjects and obese subjects are distinct entities at all stages of glucose tolerance.

A cell-free protein synthesis system from insect cells.

The newly developed Transdirect in vitro translation system for mRNA templates utilizes an extract from cultured Spodoptera frugiperda 21 (Sf21) insect cells. An expression vector, pTD1, which includes a 5'-untranslated region (UTR) sequence from a baculovirus polyhedrin gene as a translational enhancer, designed to obtain maximum performance from the insect cell-free protein synthesis system. The combination of insect cell extract and the expression vector results in protein productivity of about 50 µg/mL of the translation reaction mixture. This is the highest protein productivity yet recorded among commercialized cell-free protein synthesis systems based on animal extracts.

Radiofrequency ablation combined with transarterial chemoembolization for intermediate hepatocellular carcinoma.

AIM: Radiofrequency ablation therapy (RFA) combined with transarterial chemoembolization (TACE) (combination therapy) is effective for early-stage hepatocellular carcinoma (HCC). The aim of this study was to compare the long-term effects of combination therapy with supportive care alone for intermediate HCC. METHODS: The study included 58 patients with intermediate HCC who received combination therapy (n = 34) or supportive care alone (n = 24). The inclusion criteria were a single nodule of more than 50 mm in diameter or two to three nodules, each measuring more than 30 mm in diameter, or more than three nodules, no vascular invasion and no extrahepatic metastasis. RESULTS: The overall survival rates at 1, 2, 3 and 5 years of the combination therapy group (91%, 65%, 53% and 27%, respectively) were significantly better (P < 0.0001) than those of the supportive care group (42%, 8%, 8% and 0%, respectively). Multivariate analysis identified treatment modality (combination therapy vs supportive care alone: P < 0.0001, risk ratio [RR] = 4.290 [95% confidence interval [CI] = 2.157-8.529]) and serum α-fetoprotein (P = 0.017, RR = 2.318 [95% CI = 1.166-4.610]) as independent and significant factors of overall survival. CONCLUSION: The combination of TACE and RFA is a safe and effective therapy in patients with intermediate HCC.

Long-term outcome of elderly patients (75 years or older) with hepatocellular carcinoma.

AIM: The aim of this study was to evaluate the long-term outcome of elderly patients with hepatocellular carcinoma (HCC) aged 75 years or older. METHODS: The study included 422 patients with HCC, who were divided into two age groups: 75 years or older (n = 140) and younger than 75 (n = 282). Outcomes were compared between the two groups. RESULTS: The number of elderly patients treated with supportive care alone (33 patients; 24%) was significantly higher than younger patients (30 patients; 11%, P < 0.01). The 1-, 3-, 5- and 7-year overall survival rates of the elderly patients (81%, 55%, 39% and 23%, respectively) were worse than those of younger patients (85%, 64%, 49% and 36%, respectively, P = 0.042). However, the overall survival rate of the elderly group after excluding 63 patients treated with supportive care alone, was similar to that of the younger group (P = 0.615). Multivariate analysis identified age, total bilirubin levels, albumin levels, serum des-γ-carboxy prothrombin levels, tumor size, number of HCC nodules, vascular invasion, extrahepatic metastasis and treatment modality as independent and significant factors of overall survival. CONCLUSION: Advanced age is a negative prognostic factor in patients with HCC due to the tendency for frequent use of conservative treatment rather than locoregional or surgical treatment.

Upper limit of fasting plasma glucose level defined by oral glucose tolerance test in Japanese subjects.

AIMS: There are conflicting interpretations regarding the normal fasting plasma glucose level in Japanese subjects. We therefore aimed to define the upper limit of fasting plasma glucose level. METHODS: A total of 962 subjects who had a 75-g oral glucose tolerance test were examined. Subjects were divided into two groups - post-load normal glycemic group (2-h plasma glucose <140 mg/dL) and post-load hyperglycemic group (2-h plasma glucose≥140 mg/dL). RESULTS: There were 434 subjects with post-load normal glycemia and 528 subjects with post-load hyperglycemia. Receiver operating characteristic curve (ROC) demonstrated that the optimal cut-off value for predicting post-load hyperglycemia was a fasting plasma glucose of 99 mg/dL (area under ROC curve=0.81), which had a sensitivity, specificity, and overall diagnostic accuracy of 68%, 81%, 74%, respectively. CONCLUSIONS: These data suggest that for predicting post-load hyperglycemia, the optimal cut-off value of fasting plasma glucose was 99 mg/dL in Japanese subjects. Thus, the current cut-off value of fasting plasma glucose of 110 mg/dL in Japan might be lowered.

Meaning of upper limit of normal range of post-load 1-h plasma glucose level defined by oral glucose tolerance test in Japanese subjects.

AIMS/INTRODUCTION: To identify upper limit post-load 1-h plasma glucose (1-h PG) after 75-g oral glucose test in a Japanese population. MATERIALS AND METHODS: A total of 918 subjects were enrolled. We divided the subjects into two groups: normal 2-h post-load plasma glucose (2-h PG; <140 mg/dL) and impaired 2-h PG group (≥140 mg/dL). RESULTS: A total of 417 subjects had normal 2-h PG and 501 had impaired 2-h PG. The receiver operating characteristic (ROC) curve showed that the optimal cut-off value of 1-h PG was 179 mg/dL (area under ROC curve = 0.89), providing that the sensitivity, specificity, and positive and negative predictive value were 85, 79, 82 and 83%, respectively. The subjects with 1-h PG < 179 mg/dL consisted of 0.5% diabetes and 99.5% non-diabetes, whereas those with 1-h PG ≥ 179 mg/dL consisted of 26.9% diabetes and 73.1% non-diabetes (P < 0.01). Furthermore, there was a significant correlation between 1-h PG and 2-h PG (r (2) = 0.57, P < 0.01). CONCLUSIONS: These data suggested that 179 mg/dL is the upper limit of the normal range of post-load of 1-h PG in a Japanese population. Thus, the subjects with 1-h PG ≥ 179 mg/dL might be at risk of developing future diabetes. Therefore, appropriate prospective study should be carried out to test this hypothesis.

A simple fed-batch method for transcription and insect cell-free translation.

We tested a one batch reaction method for the transcription and the insect cell-free translation from undigested plasmids without any centrifugation steps. The efficiency of protein synthesis reached 74-112% of that achieved using the conventional procedure. This simplified method will help expedite the high throughput insect cell-free protein production.

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers.

BACKGROUND: There are few blood tests for an efficient detection of hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection. METHODS: The abilities of quantitative analyses of 7 genes hypermethylation in serum DNA, α-fetoprotein (AFP) and prothrombin-induced vitamin K absence II (PIVKA-II), and various combinations to detect HCC were evaluated in a training cohort of 164 HCV-infected patients (108 HCCs; 56 non-HCCs). An optimal hybrid detector, built using data for 2 methylated genes (SPINT2 and SRD5A2), AFP, and PIVKA-II, achieved the most satisfactory ability to detect HCC in the training cohort. We evaluated the ability of the optimal hybrid detector to detect HCC in an independent validation cohort of 258 consecutive HCV-infected patients (112 HCCs; 146 non-HCCs) who were newly enrolled in 4 distinct institutes. RESULTS: In the validation cohort of 258 patients, accuracy, sensitivity, and specificity of the hybrid detector for detection of HCC were 81.4%, 73.2%, and 87.7%, respectively. Notably, even when detecting HCC ≤ 2 cm in diameter, the hybrid detector maintained markedly high abilities (84.6% accuracy, 72.2% sensitivity, 87.7% specificity). Youden's index (sensitivity+specificity - 1) for HCC ≤ 2cm was 0.60, vastly much superior to the 0.39 for AFP at a cut-off value of 20 ng/ml and the 0.28 for PIVKA-II at a cut-off value of 40 mAU/ml. CONCLUSIONS: These results show that the optimal hybrid blood detector can detect HCV-related HCC more accurately.

Recent progress in the management of hepatocellular carcinoma detected during a surveillance program in Japan.

AIM: This study explored recent improvements in the management of hepatocellular carcinoma (HCC) diagnosed during surveillance. METHODS: The subjects were 1074 patients with HCC, subdivided into three groups. Group A comprised 211 patients for whom HCC was detected during periodic follow-up examinations at Kurume University School of Medicine, Group B comprised 544 patients diagnosed with HCC during periodic follow-up examinations at other institutions, and, Group C comprised 319 patients with HCC detected incidentally or because of symptoms. RESULTS: In 1995-2000 and 2001-2006, 91% and 91% of group A, 68% and 70% of group B, and 27% and 26% of group C patients with HCC, respectively, met the Milan criteria. For groups A and B, the proportions of patients with Child-Pugh class A and use of promising treatment increased in the later periods compared to those diagnosed during the earlier periods (group A, Child-Pugh class A, 72% vs 58% [P = 0.040], receiving treatment, 90% vs 70% [P < 0.0001]; group B, Child-Pugh class A, 71% vs 62% [P = 0.031]; receiving treatment, 72% vs 52% [P < 0.0001], respectively). The cumulative survival rates of the 405 patients with HCC detected in the latter 6 years tended to be better than those for patients diagnosed in the former 6 years (350 patients) (4 years, 58% vs 50% [P = 0.0349]). CONCLUSION: The use of promising treatment and prognosis have improved in the last 6 years for patients with HCC diagnosed through surveillance relative to those identified in 1995-2000.