[Rectal tumor differentiating into neuroendocrine lineage:a case report].

A 79-year-old woman underwent colonoscopy that revealed a 30-mm-sized nodular, mixed-type, lateral spreading tumor-granular in the lower rectum. Endoscopic submucosal dissection was performed, and the pathological findings indicated a mostly adenoma-type tumor with synaptophysin, cluster of differentiation 56-positive, and chromogranin A-negative associated with neuroendocrine carcinoma. Surgical resection was performed owing to vascular invasion, and the lymph node metastasis of the endocrine carcinoma component was observed. Thus, we reported a rare case of the coexistence of adenoma and neuroendocrine carcinoma.

Usefulness of the G8 Geriatric Assessment Tool as a Prognostic Factor in Gemcitabine Plus Nab-paclitaxel Combination Therapy for Elderly Patients with Pancreatic Cancer.

Introduction: The usefulness of various prognostic factors for advanced pancreatic cancer (APC) has been reported, but the number of elderly patients in these studies is disproportionately fewer than those in general practice. This study aimed to examine the prognostic factors for elderly patients with APC receiving gemcitabine plus nab-paclitaxel (GnP) considering the G8 geriatric assessment tool. Methods: We retrospectively analyzed 77 elderly (≥65 years old) patients with APC who received GnP as first-line chemotherapy at our hospital. We used the receiver operating characteristic curve to set the optimal cutoff value for G8. Univariate and multivariate Cox regression models were applied to study independent prognostic factors. Results: The progression-free survival was 5.5 months, and the overall survival (OS) was 12.0 months in all patients. The most optimal cutoff of G8 was 10.5. OS of G8 ≥10.5 patients was superior to that of G8 <10.5 patients (18.5 versus 8.0 months). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status 1 (hazard ratio [HR] 3.00, p = 0.02), neutrophil-lymphocyte ratio ≥3.9 (HR 2.73, p = 0.03), and G8 geriatric assessment <10.5 (HR 5.38, p < 0.001) were independent negative prognostic factors. Conclusions: G8 is useful for predicting prognoses in elderly patients with APC receiving GnP.

Usefulness of Cell-Free Human Telomerase Reverse Transcriptase Mutant DNA Quantification in Blood for Predicting Hepatocellular Carcinoma Treatment Efficacy.

Although the usefulness of liquid biopsy as a biomarker in the treatment of hepatocellular carcinoma (HCC) has been suggested, its usefulness in transcatheter arterial chemoembolization (TACE) or tyrosine kinase inhibitor (TKI) therapies has not been reported in detail. In this study, we investigated the clinical value of a cell-free (cf)DNA quantification system targeting the human telomerase reverse transcriptase (hTERT) promoter mutation in advanced HCC treatment. Plasma from 67 patients with advanced HCC, treated with TACE and TKI, was used for extraction of cfDNA. We defined cfDNA with the hTERT promoter C228T mutation as circulating mutant DNA (mutant DNA) and without the mutation as circulating wild-type DNA (wild-type DNA). We analyzed the changes in mutant and wild-type DNA levels during HCC treatment and examined the relationship between changes in the cfDNA level and the clinical course. Mutant DNA was detected in 73.1% (49/67) of the patients during HCC treatment. In univariate analysis, factors associated with detection of mutant DNA before treatment were the intrahepatic maximum tumor diameter (P = 0.015) and protein induced by vitamin K absence (PIVKAII) (P = 0.006). The degree of mutant DNA change after TACE was significantly correlated with tumor volume (P < 0.001), reflecting the treated tumor volume. Responders with peak cfDNA levels within 1 week of TKI initiation had significantly better progression-free survival than nonresponders (P = 0.004). Conclusion: Changes in blood hTERT promoter mutant DNA levels during TACE or TKI treatment indirectly reflect the amount of HCCs and are useful for predicting long-term treatment responses.

Fracture of a Self-expandable Metallic Stent Inserted for Malignant Gastric Outlet Obstruction.

Duodenal stenting has gradually been established as the first-line treatment for malignant gastric outlet obstruction (GOO). We encountered a case of duodenal stent fracture in a 76-year-old woman with gastric cancer and GOO. She underwent self-expandable metallic stent (SEMS) placement. The SEMS was found to be fractured 4 weeks after its placement. We removed the broken part of the stent and placed a second SEMS. SEMS fracture is a rare and - to the best of our knowledge - unreported complication; hence, clinicians and their patients should be aware of this possibility.

Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings.

AIM: The landscape of cancer-related genetic aberrations in hepatocellular carcinoma (HCC) has gradually become clear through recent next-generation sequencing studies. However, it remains unclear how genetic aberrations correlate with imaging and histological findings. METHODS: Using 117 formalin-fixed paraffin-embedded specimens of primary liver tumors, we undertook targeted next-generation sequencing of 50 cancer-related genes and digital polymerase chain reaction of hTERT. After classifying tumors into several imaging groups by hierarchal clustering with the information from gadoxetic acid enhanced magnetic resonance imaging, contrast-enhanced computed tomography, contrast-enhanced ultrasound, and diffusion-weighted imaging magnetic resonance imaging, the correlation between genetic aberrations and imaging and histology were investigated. RESULTS: Most frequent mutations were hTERT (61.5%), followed by TP53 (42.7%), RB1 (24.8%), and CTNNB1 (18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence of hTERT mutations tended to increase with the advancement of imaging/histological grades (P = 0.026 and 0.13, respectively), whereas no such tendency was evident for TP53 mutation (P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) of hTERT did not change (P = 0.36 and 0.14, respectively) in association with imaging/histological grades, TP53 VF increased significantly (P = 0.004 and <0.001, respectively). In multivariate analysis, stage III or IV (hazard ratio, 3.64; P = 0.003), TP53 VF ≥ 50% (hazard ratio, 3.79; P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. CONCLUSIONS: Increased prevalence of hTERT mutation and increased TP53 mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.

Relationship between presarcopenia and event occurrence in patients with primary hepatocellular carcinoma.

Presarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). The Japan integrated staging (JIS) score is a prognostic method that combines the Child-Turcotte-Pugh classification and the tumor-node-metastasis (TNM) staging for HCC. We investigated the relationship between presarcopenia, the JIS score, and prognosis in patients with primary HCC. This retrospective study included 153 patients with primary HCC who were hospitalized from October 2011 to March 2018 at Municipal Hospital of Kofu. The skeletal muscle mass was measured using simplified psoas muscle mass index (PMI) based on CT imaging, and PMI using the volume analyzer SYNAPSE VINCENT ver3.0. We diagnosed presarcopenia based on the cut off value according to the assessment criteria for sarcopenia in liver disease defined by the Japan Society of Hepatology. Forty-three patients (28%) were diagnosed with presarcopenia. The median event-free survival was significantly worse in patients with presarcopenia than those without presarcopenia (P = 0.016). In multivariate analysis, presence of presarcopenia, JIS score ≥3, alpha-fetoprotein ≥200 ng/ml, and prothrombin induced by vitamin K absence-II ≥ 200 mAU/ml were significant prognostic factors. Among the patients with JIS scores ≥3, there was no difference in the event occurrence rate with presence of presarcopenia (P = 0.96). Among the patients with JIS scores ≤2, the median event-free-survival was significantly shorter in those with presarcopenia than those without presarcopenia (P = 0.045). Presarcopenia was an independent prognostic factor in patients with primary HCC. In patients with JIS scores ≤2, the median event-free survival was significantly shorter in those with presarcopenia compared to those without presarcopenia. In the patients with JIS scores ≥3, there was no difference in the event occurrence rates in those with and without presarcopenia.

Extravasation and fluid collection on computed tomography imaging in patients with colonic diverticular bleeding.

OBJECTIVE: We evaluated the characteristics of patients with diverticular bleeding in whom emergency endoscopy should be proactively performed and those in whom it is unnecessary for spontaneous hemostasis following conservative treatment. METHODS: This study involved 132 patients in whom diverticular bleeding was diagnosed on lower gastrointestinal endoscopy. We evaluated the rate of identification of the bleeding diverticulum during endoscopy and the rate of spontaneous hemostasis following conservative treatment. RESULTS: In 26 patients (20%), bleeding diverticulum was identified during endoscopy. Extravasation or fluid collection on CT imaging was an important factor of successful identification of the bleeding source on endoscopy. Of the 104 patients in the conservative treatment group, 91 (87%) were able to be discharged after spontaneous hemostasis. Univariate analysis revealed a high rate of spontaneous hemostasis in patients without extravasation and fluid collection on CT imaging, those without adhesion of blood during endoscopy, those without diabetes, and those with a hemoglobin level ≥10 g/dL. CONCLUSION: In patients with colonic diverticular bleeding, extravasation or fluid collection on CT is an important factor related to the identification of the bleeding diverticulum. Patients without characteristic CT findings had a high rate of spontaneous hemostasis after conservative treatment. BACKGROUND: Diverticular bleeding is the most frequent cause of lower gastrointestinal bleeding accounting for 20%-40% of all cases in Japan and 20%-48% of all those in the Western countries[1, 2]. The prevalence of colonic diverticula tends to increase with age; thus, the overall prevalence of diverticular bleeding is expected to increase in the future. In Japan, the Japanese Gastroenterological Association published guidelines on colonic diverticulitis in 2017; these guidelines recommend the performance of lower gastrointestinal endoscopic examination within 24 h in patients with lower gastrointestinal bleeding suspected to be diverticular bleeding[3]. It has been reported that, for patients with lower gastrointestinal bleeding, urgent endoscopy helps avoid embolotherapy, colectomy, massive blood transfusion, and repeat bleeding[1, 4, 5]. However, it is often difficult to identify the bleeding point [6]; further, there are many challenging cases wherein it is difficult to decide whether urgent endoscopy should be performed in situations where there is insufficient medical staff, such as during nighttime and on holidays. Bleeding is reported to stop spontaneously with conservative treatment alone in 70% of diverticular bleeding cases[7, 8]. In particular, when determining the treatment policy for diverticular bleeding and in the case of patients at high risk of complications following endoscopy, such as older patients, those with poor performance status or cardiovascular disease, and those in whom spontaneous hemostasis can be expected, urgent endoscopy should be avoided, and elective endoscopy should be selected. Therefore, the type of cases wherein urgent endoscopy is effective and the type wherein it is unnecessary need to be clarified. Thus far, there have been very few reports of the characteristics of patients with diverticular bleeding in whom spontaneous hemostasis was achieved. We aimed to assess the characteristics of patients in whom emergency endoscopy should be proactively performed and those for whom it is unnecessary. Thus, we retrospectively analyzed the identification rate for the responsible diverticulum in patients with diverticular bleeding and the rate of spontaneous hemostasis following conservative treatment.

Utility of Prognostic Prediction Models in the Terminal Stage of Gastrointestinal Cancer.

PURPOSE: For patients receiving palliative care, information about prognosis is important to help them set priorities and expectations for care and to assist clinicians in decision-making. The purpose of this study was to investigate prognostic models applicable to the terminal stage of gastrointestinal cancer, especially in terms of accuracy of prediction regarding 3-week survival. METHODS: We validated retrospectively the accuracy of a prognosis prediction model for 354 end-stage gastrointestinal cancer patients who underwent palliative care at our hospital. Using receiver operating characteristic analysis and the area under the curve (AUC), we selected the cut-off value for 3-week survival and evaluated the predictive ability using sensitivity, specificity, positive predictive value, negative predictive value, and accurate diagnosis rate. RESULTS: In our analysis of various models, Palliative Prognostic Index (PPI) and Biological Prognostic Score (BPS) version 3 showed excellent predictive performance with AUCs of 0.85 and 0.83, respectively, and accurate diagnosis rates of 80.0 and 79.0, respectively. BPS version 2 showed fair predictive performance with an AUC of 0.76 and an accurate diagnosis rate of 72.0. Using these models, stratification of prognostic prediction was possible. CONCLUSIONS: PPI and BPS were found to be accurate prediction models for short-term survival of terminal gastrointestinal cancer patients.

Hepatitis B virus (HBV)-infected patients with low hepatitis B surface antigen and high hepatitis B core-related antigen titers have a high risk of HBV-related hepatocellular carcinoma.

AIM: Although the viral markers hepatitis B surface antigen (HBsAg) and hepatitis B core-related antigen (HbcrAg) could reflect intrahepatic hepatitis B virus (HBV) replication activity and constitute important biomarkers for hepatocellular carcinoma (HCC), the value of using these two markers in combination for assessing HCC risk has not been clarified in detail. METHODS: Four hundred and forty-nine consecutive patients with chronic HBV infection were included in the study and the association of HBsAg and HBcrAg with HCC risk was investigated cross-sectionally, as well as longitudinally. RESULTS: When the high value cut-offs of HBsAg and HBcrAg were defined as 3.0 log IU/mL and 3.0 log U/mL, respectively, patients with a history of HCC were found frequently in the low HBsAg group (P = 0.002) and high HBcrAg group (P < 0.001). When HBsAg and HBcrAg were combined, an HCC history was most frequent in the subset with low HBsAg and high HBcrAg, among the HBeAg-negative patients (odds ratio [OR], 7.83; P < 0.001), irrespective of nucleos(t) ide analogue (NA) therapy (NA: OR, 4.76; P < 0.001; non-NA: OR, 9.60; P < 0.001). In a longitudinal analysis of the subsequent development of HCC, carried out on the 338 patients without an HCC history at enrollment, HCC developed significantly more frequently in the low HBsAg/high HBcrAg group (P = 0.005). CONCLUSIONS: Patients with low HBsAg/high HBcrAg values are at high risk of developing HBV-related HCC, according to this cross-sectional and longitudinal analysis, indicating that the combination of HBsAg and HBcrAg values is an excellent biomarker for assessing HCC risk.

Performance status and neutrophil-lymphocyte ratio are important prognostic factors in elderly patients with unresectable pancreatic cancer.

BACKGROUND: The usefulness of various prognostic factors for pancreatic cancer (PC) has been reported, but the number of elderly patients in these studies is disproportionately fewer compared with those in everyday practice. The purpose of this study was to investigate the prognostic factors for unresectable PC in elderly patients. METHODS: We retrospectively analyzed 67 elderly (age ≥75 years) patients with unresectable PC who underwent chemotherapy between January 2006 and December 2014 at our hospital. Univariate and multivariate Cox regression models were applied to investigate independent prognostic factors. RESULTS: Multivariate analysis revealed that an increased neutrophil-lymphocyte ratio (NLR) [hazard ratio (HR) 1.91, P=0.03] and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 (HR 2.74, P=0.01) were independent negative prognostic factors. CONCLUSIONS: The two prognostic factors identified herein are useful in the identification of patients with a poor prognosis and subsequent administration of supportive care alone, which may help avoid the unnecessary adverse effects and complications of systemic chemotherapy.

Semiannual Imaging Surveillance Is Associated with Better Survival in Patients with Non-B, Non-C Hepatocellular Carcinoma.

Since it remains elusive whether and how the imaging surveillance affects the survival in patients with non-B, non-C hepatocellular carcinoma (NBNC-HCC), we conducted this retrospective study which investigated the association between the semiannual surveillance prior to HCC diagnosis and the survival in patients with the initial diagnosis of HCC induced by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections (N = 141) and non-B, non-C etiology (N = 30). It was demonstrated that surveillance was less frequently performed in the NBNC-HCC patients compared to that in HCC patients with HBV and/or HCV infections (B/C-HCC patients), and the survival was unfavorable in NBNC-HCC patients. On the other hand, the survival of NBNC-HCC patients with semiannual surveillance was significantly favorable than those patients without semiannual surveillance, and the survival was similar between B/C-HCCs and NBNC-HCCs with semiannual surveillance. In conclusion, though NBNC-HCC patients compared to B/C-HCC patients had poorer prognosis overall, these NBNC-HCC patients with semiannual surveillance had a better survival almost equivalent to the survival of B/C-HCC patients with semiannual surveillance, demonstrating the clinical utility of the semiannual imaging surveillance program for NBNC-HCCs.

Liver stiffness measurement for risk assessment of hepatocellular carcinoma.

AIM: Liver fibrosis is a risk factor for hepatocellular carcinoma (HCC), but at what fibrotic stage the risk for HCC is increased has been poorly investigated quantitatively. This study aimed to determine the appropriate cut-off value of liver stiffness for HCC concurrence by FibroScan, and its clinical significance in hepatitis B virus (HBV), hepatitis C virus (HCV) and non-B, non-C (NBNC) liver disease. METHODS: Subjects comprised 1002 cases (246 with HCC and 756 without HCC) with chronic liver disease (HBV, 104; HCV, 722; and NBNC, 176). RESULTS: Liver stiffness was significantly greater in all groups with HCC, and the determined cut-off value for HCC concurrence was more than 12.0 kPa in those with HCV, more than 8.5 kPa in those with HBV and more than 12.0 kPa in those with NBNC. Liver stiffness of more than 12.0 kPa was an independent risk factor for new HCC development in HCV. For HCV, risk factors for HCC concurrence were old age, male sex, low albumin, low platelets and liver stiffness, while for HBV they were old age, low platelets and liver stiffness, and for NBNC they were old age, elevated α-fetoprotein and liver stiffness. CONCLUSION: Liver stiffness cut-off values and their association with HCC concurrence were different depending on the etiology. In HCV, liver stiffness of more than 12.0 kPa was an independent risk factor for new HCC development. Collectively, determining the fibrotic cut-off values for HCC concurrence would be important in evaluating HCC risks.

[Case of leptomeningeal carcinomatosis with esophageal carcinoma presenting with neurological signs].

A 72-year-old male was admitted because of hearing impairment, blurred vision, right hemifacial numbness, and difficulty walking. Brain magnetic resonance imaging revealed two enhancing lesions with infiltration around the cranial nerves indicating either metastatic brain tumors or meningeal carcinomatosis. Cytological examination of the cerebrospinal fluid revealed malignant cells with keratotic changes. Upper gastrointestinal endoscopy was performed, which revealed type 1 squamous cell carcinoma of the esophagus;this led to the diagnosis of leptomeningeal carcinomatosis. In this report, we present a rare case of esophageal carcinoma accompanied by meningeal carcinomatosis diagnosed on the basis of neurological symptoms.

Hepatocellular carcinoma risk assessment using gadoxetic acid-enhanced hepatocyte phase magnetic resonance imaging.

AIM: To investigate whether the patients with hypovascular liver nodules determined on the arterial phase and hypointensity on the hepatocyte phase gadoxetic acid-enhanced magnetic resonance imaging (hypovascular hypointense nodules) are at increased risk of hepatocarcinogenesis, we assessed subsequent typical hepatocellular carcinoma (HCC) development at any sites of the liver with and without such nodules. METHODS: One hundred and twenty-seven patients with chronic hepatitis B or C and without a history of HCC, including 68 with liver cirrhosis, were divided into those with (non-clean liver group, n = 18) and without (clean liver group, n = 109) hypovascular hypointense nodules. All the patients were followed up for 3 years, and HCC development rates and risk factors were analyzed with the Kaplan-Meier method and the Cox proportional hazard model, respectively. RESULTS: A total of 17 patients (10 in the non-clean liver group and seven in the clean liver group) developed typical HCC. Cumulative 3-year rates of HCC development were 55.5% in the non-clean liver group and 6.4% in the clean liver group (P < 0.001), and those at the different sites from the initial nodules was also higher in the non-clean liver group (22.2%) than the clean liver group (6.4%) (P = 0.003). Multivariate analysis identified older age (P = 0.024), low platelet counts (P = 0.017) and a non-clean liver (P < 0.001) as independent risk factors for subsequent HCC development. CONCLUSION: Patients with hypovascular hypointense liver nodules are at a higher risk for HCC development at any sites of the liver than those without such nodules.

Deep-sequencing analysis of the association between the quasispecies nature of the hepatitis C virus core region and disease progression.

Variation of core amino acid (aa) 70 of hepatitis C virus (HCV) has been shown recently to be closely correlated with liver disease progression, suggesting that the core region might be present as a quasispecies during persistent infection and that this quasispecies nature might have an influence on the progression of disease. In our investigation, the subjects were 79 patients infected with HCV genotype 1b (25 with chronic hepatitis [CH], 29 with liver cirrhosis [LC], and 25 with hepatocellular carcinoma [HCC]). Deep sequencing of the HCV core region was carried out on their sera by using a Roche 454 GS Junior pyrosequencer. Based on a plasmid containing a cloned HCV sequence (pCV-J4L6S), the background error rate associated with pyrosequencing, including the PCR procedure, was calculated as 0.092 ± 0.005/base. Deep sequencing of the core region in the clinical samples showed a mixture of "mutant-type" Q/H and "wild-type" R at the core aa 70 position in most cases (71/79 [89.9%]), and the ratio of mutant residues to R in the mixture increased as liver disease advanced to LC and HCC. Meanwhile, phylogenetic analysis of the almost-complete core region revealed that the HCV isolates differed genetically depending on the mutation status at core aa 70. We conclude that the core aa 70 mixture ratio, determined by deep sequencing, reflected the status of liver disease, demonstrating a significant association between core aa 70 and disease progression in CH patients infected with HCV genotype 1b.

Correlation between pretreatment viral sequences and the emergence of lamivudine resistance in hepatitis B virus infection.

The emergence of amino acid or nucleotide substitutions leads to lamivudine resistance in hepatitis B virus (HBV) infected patients. The aim of this study was to investigate whether viral sequences help predict the emergence of lamivudine resistance. The study subjects comprised 59 consecutive patients infected with HBV treated with daily therapy of 100 mg lamivudine. Among those, 32 patients with adequate pretreatment serum preservation were investigated for the correlation between viral amino acid substitutions and the appearance of lamivudine resistance with consideration of clinical background by determining dominant HBV full open reading frames. Viral resistance to lamivudine emerged in 28 of 59 patients (47%) in a median period of 2.45 years. Sequence comparisons of HBV genomes between patients who later developed lamivudine resistance and patients who did not revealed the existence of significant differences between the two groups in the pre-S1 84 (P = 0.042), pre-S2 1 (P = 0.017) and 22 (P = 0.015), and polymerase tp 95 (P = 0.046), judged by a log-rank test. Viral sequence analyses revealed the presence of amino acid substitutions in HBV pre-S1 and pre-S2 that may be associated with the emergence of lamivudine resistance during chronic HBV infection.

Cross-validation of MR elastography and ultrasound transient elastography in liver stiffness measurement: discrepancy in the results of cirrhotic liver.

PURPOSE: To evaluate individual differences in liver stiffness measurement using both MR elastography (MRE) and ultrasound transient elastography (UTE) in patients with chronic liver disease. MATERIALS AND METHODS: This study included 80 patients with chronic liver disease who underwent both UTE and MRE. MRE and UTE were performed using a pneumatic driver (60 Hz) and an ultrasound probe with a vibrator (50 Hz), respectively. Liver stiffness data measured using the two techniques (µ(UTE) and µ(MRE) ) were compared with respect to shear modulus. The patients were subdivided into four quartiles on the basis of average of the µ(UTE) and µ(MRE) values for each patient. RESULTS: The analysis of the 4 quartile groups revealed that µ(UTE) was significantly higher than µ(MRE) in the two most stiff liver groups: µ(UTE) versus µ(MRE) , 7.5 (1.2) versus 6.0 (0.72) kPa for the group with [µ(UTE) + µ(MRE) ]/2 of 5.6-8.0 kPa; 15.1(4.2) versus 6.7 (1.4) kPa for the group with >8.0 kPa. However, in the least stiff liver group (i.e., the group with [µ(UTE) + µ(MRE) ]/2 < 3.2 kPa), µ(UTE) was significantly lower than µ(MRE) . CONCLUSION: The shear modulus measured by UTE and MRE are not equivalent, especially in patients with stiff livers.

Analysis of viral amino acids sequences and the IL28B SNP influencing the development of hepatocellular carcinoma in chronic hepatitis C.

BACKGROUND AND AIMS: The association between hepatitis C virus (HCV) sequences with interleukin 28B (IL28B) single-nucleotide polymorphism (SNP) in the development of hepatocellular carcinoma (HCC) has not been well clarified. METHODS: Complete HCV open-reading frame sequences were determined in 20 patients developing HCC and 23 non-HCC patients with HCV-1b infection in two distant time points. An additional 230 patients were studied cross-sectionally for core and NS5A sequences with HCC development. Among them, 98 patients with available samples were investigated for changes in viral core sequences over time. Finally, IL28B SNPs and HCC development were investigated in 228 patients. RESULTS: During observation period (HCC for 10.8 years, and non-HCC for 11.1 years), changes in core a.a. 70 and three amino acid positions in NS5A were characteristics of the patients developing HCC. In 230 patients, Q (glutamine) or H (histidine) to R (arginine) ratio at core a.a. 70 was significantly higher in the HCC group (HCC group 43:22 vs. non-HCC group 66:99, p = 0.001). A change in core R70Q was observed over time in 11 patients associated with a decrease in platelets (p = 0.005) and albumin (p = 0.005), while a Q70R change was observed in 4 patients without associated changes in platelets (nonsignificant) and albumin (nonsignificant). IL28B SNP showed significant correlation with the core a.a. 70 residue. There was no evident link between IL28B SNPs and the occurrence of HCC. CONCLUSIONS: Hepatitis C virus core a.a. 70 residue is associated with liver disease progression and is independent factor for HCC development in genotype-1b infection. IL28B SNPs are related to core a.a. 70 residue, but not to HCC. The functional relevance of core a.a. 70 residue in hepatitis C pathogenesis should be further investigated.

Outcome of hypovascular hepatic nodules revealing no gadoxetic acid uptake in patients with chronic liver disease.

PURPOSE: To elucidate the natural history of hypovascular nodules that appear hypointense on hepatocyte-phase gadoxetic acid-enhanced MR images by focusing on hypervascularization over time. MATERIALS AND METHODS: In this study, 135 hypovascular nodules revealing no gadoxetic acid uptake in 53 patients were examined. All nodules were retrospectively examined using serial follow-up computed tomography (CT) and MRI examinations until hypervascularity was observed on arterial-phase dynamic CT or gadoxetic acid-enhanced MR images, or on CT during hepatic arteriography. Logistic regression analysis was used to investigate the association between hypervascularization and MR findings including a presence of fat assessed by a signal drop on opposed-phase T1-weighted images. RESULTS: Of the 135 nodules, 16 underwent hypervascularization. The size of the nodules and the presence of fat in the nodules were independent indicators of hypervascularization. The 1-year cumulative risk of hypervascularization was 15.6%. This risk was significantly increased in the case of nodules >10 mm (37.6%, P < 0.01) and fat-containing nodules (26.5%, P < 0.01). CONCLUSION: Hypovascular nodules that appear hypointense on hepatocyte-phase gadoxetic acid-enhanced MR images may progress to conventional hypervascular hepatocellular carcinoma. Nodules more than 10 mm in diameter and containing fat are at high risk for developing hypervascularization.

Double-dose gadoxetic Acid-enhanced magnetic resonance imaging in patients with chronic liver disease.

OBJECTIVES: determine the effect of double-dose gadoxetic-acid (Gd-EOB-DTPA) on lesion-liver contrast ratio in arterial- and hepatocyte-phase images and arterial-phase image quality in patients with chronic liver disease. MATERIALS AND METHODS: the ethics committee at our institute approved this study. This study included 28 patients (13 with Child-Pugh class A and 15 with class B) with 54 hepatocellular carcinomas. All patients received the standard Gd-EOB-DTPA dose (0.025 mmol/kg bodyweight) and double dose (0.050 mmol/kg bodyweight). The lesion-liver contrast ratio was evaluated in arterial- and hepatocyte-phase images. The artifacts in arterial-phase images were evaluated with a 4-point scale. Wilcoxon signed-rank test were used for comparisons. RESULTS: the hepatocyte-phase lesion-liver contrast ratio after the double dose was significantly higher than that after the standard dose in patients with Child-Pugh class B disease(standard dose vs. double dose; 0.20 ± 0.16 vs. 0.25 ± 0.17; P < 0.0001); however, the ratio after both the standard and double doses was equivalent in patients with Child-Pugh class A disease (0.35 ± 0.18 vs. 0.35 ± 0.14; P = 0.3038). The double dose significantly increased the arterial-phase lesion-liver contrast ratio (0.34 ± 0.19 vs. 0.58 ± 0.33; P < 0.0001). The artifacts in the arterial-phase images were more prominent after the standard dose (2.7 vs. 2.4 for reader 1, 2.8 vs. 2.4 for reader 2; P = 0.0195 and 0.0010). CONCLUSIONS: administration of double dose of Gd-EOB-DTPA provided better arterial enhancement of hepatocellular carcinomas in patients with chronic liver disease, and also improved the lesion-liver contrast in hepatocyte-phase images in patients with Child-Pugh class B disease.