Hepatic FATP5 expression is associated with histological progression and loss of hepatic fat in NAFLD patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are characterized by the accumulation of excess hepatic fat. However, in the progression from NASH to cirrhosis, hepatic fat is often lost. Our aim was to elucidate the mechanism underlying hepatic fat loss during NASH progression. METHODS: Liver biopsies were performed at The University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD and 14 patients with cryptogenic cirrhosis who were not being treated with any diabetes or dyslipidemia drugs. Among them, 70 patients underwent liver biopsy after an overnight fast, and 90 patients were biopsied 5 h after an oral glucose tolerance test. Expression differences in genes encoding several fatty acid metabolism-related factors were examined and correlated with hepatic histological changes based on NAFLD activity scores. Prospective patient follow-up continued until June 2018. RESULTS: The level of fatty acid transport protein 5 (FATP5), which is associated with free fatty acid intake, was significantly and inversely correlated with features of histological progression, including ballooning and fibrosis. This was confirmed by immunohistochemical analysis. Transcript levels of genes encoding fatty acid metabolism-related proteins were comparable between NASH with severe fibrosis and cryptogenic cirrhosis. Furthermore, a prospective cohort study demonstrated that low FATP5 expression was the most significant risk factor for hepatic fat loss. CONCLUSIONS: Decreased hepatic FATP5 expression in NAFLD is linked to histological progression, and may be associated with hepatic fat loss during NASH progression to cirrhosis.

Primary tumor of the ureteral stump after a radical nephrectomy for renal cell carcinoma: case report and literature review.

We report a case of ureteral stump carcinoma following a radical nephrectomy for renal cell carcinoma. A 76-year-old man was diagnosed as having ascending colon cancer and a right renal carcinoma. He was treated with partial colon resection and radical nephrectomy without lymphadenectomy. The histology was renal cell carcinoma. Three years after that surgery, he complained of intermittent macrohematuria. Abdominal computed tomography (CT) suggested a solid mass in the pelvis. We then performed a biopsy with CT guidance. An epithelial tumor was suspected by immunohistochemistry. A total excision of ureter was then performed. The histology showed the features of urothelial carcinoma, G3, v(+), pT3. He received adjuvant chemotherapy with gemcitabine and cisplatin. He was free of disease for the following 11 months.

Hepatic IRS1 and ß-catenin expression is associated with histological progression and overt diabetes emergence in NAFLD patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes. Our aim was to investigate the relationship between NAFLD and impaired glucose metabolism in terms of insulin receptor substrate 1 and 2 (IRS1 and IRS2) expression in the liver. METHODS: Liver biopsy was performed at the University of Tokyo Hospital between November 2011 and March 2016 on 146 patients with NAFLD who were not being treated with any diabetes or dyslipidemia drugs. Among them, 63 underwent liver biopsy after an overnight fast, and 83 at 5 h after an oral glucose tolerance test (OGTT). Differences in messenger RNA (mRNA) levels of several glucose metabolism-related factors were determined and correlated with hepatic histological changes assessed by NAFLD activity score. We prospectively followed up with the patients until May 2017. RESULTS: Hepatic necroinflammation was significantly correlated with serum insulin levels and inversely correlated with IRS1 mRNA levels. In specimens obtained after an OGTT, hepatic necroinflammation and IRS1 expression correlated significantly with both peripheral and hepatic insulin resistance. We also found that hepatic ß-catenin and glucokinase mRNA levels were elevated in patients undergoing liver biopsy after an OGTT, especially in those with less hepatic necroinflammation and a lower degree of fibrosis. A prospective cohort study showed that ballooning is the most significant risk factor for developing diabetes. CONCLUSIONS: The decreased hepatic expression of IRS1 and ß-catenin in NAFLD is linked to histological progression such as ballooning, and might lead to diabetes as a result of impaired glucose metabolism.

The ADOPT-LC score: a novel predictive index of in-hospital mortality of cirrhotic patients following surgical procedures, based on a national survey.

AIM: We aimed to develop a model for predicting in-hospital mortality of cirrhotic patients following major surgical procedures using a large sample of patients derived from a Japanese nationwide administrative database. METHODS: We enrolled 2197 cirrhotic patients who underwent elective (n = 1973) or emergency (n = 224) surgery. We analyzed the risk factors for postoperative mortality and established a scoring system for predicting postoperative mortality in cirrhotic patients using a split-sample method. RESULTS: In-hospital mortality rates following elective or emergency surgery were 4.7% and 20.5%, respectively. In multivariate analysis, patient age, Child-Pugh (CP) class, Charlson Comorbidity Index (CCI), and duration of anesthesia in elective surgery were significantly associated with in-hospital mortality. In emergency surgery, CP class and duration of anesthesia were significant factors. Based on multivariate analysis in the training set (n = 987), the Adequate Operative Treatment for Liver Cirrhosis (ADOPT-LC) score that used patient age, CP class, CCI, and duration of anesthesia to predict in-hospital mortality following elective surgery was developed. This scoring system was validated in the testing set (n = 986) and produced an area under the curve of 0.881. We also developed iOS/Android apps to calculate ADOPT-LC scores to allow easy access to the current evidence in daily clinical practice. CONCLUSION: Patient age, CP class, CCI, and duration of anesthesia were identified as important risk factors for predicting postoperative mortality in cirrhotic patients. The ADOPT-LC score effectively predicts in-hospital mortality following elective surgery and may assist decisions regarding surgical procedures in cirrhotic patients based on a quantitative risk assessment.

Efficacy of repeat review with flexible spectral imaging color enhancement in patients with no findings by capsule endoscopy.

BACKGROUND/AIM: The efficacy of flexible spectral imaging color enhancement (FICE) ch. 1 (F1) for the detection of ulcerative lesions and angioectasias in the small intestine with capsule endoscopy (CE) has been reported. In the present study, we evaluated whether F1 could detect incremental findings in patients with no findings in a standard review mode. PATIENTS AND METHODS: In total, 52 patients (age: 60.1 ± 15.3 years; 30 males) with obscure gastrointestinal bleeding (OGIB) who underwent CE and in whom no lesion was detected in the small intestine in the standard mode (first review) were enrolled. Two experienced endoscopists independently reviewed CE videos again by F1 (second review). The following findings were defined to be significant: Ulcers, erosions, aphthas, angioectasias, tumors, and bleeding. Incremental findings at the second review were checked at F1 and in standard mode by the two reviewers (third review). Finally, the findings were confirmed by the agreement of the two reviewers at the third review. RESULTS: F1 detected five significant lesions in three patients with overt OGIB; three erosions, one aphtha, and one angioectasia. For nonsignificant lesions, F1 detected 12 red mucosas and 16 red spots. Moreover, 29 patients with 71 findings were considered false positives. CONCLUSION: F1 detected incremental significant findings in a small percentage of patients with no findings in the standard review mode. In addition, F1 showed many false-positive findings. The incremental effect of a repeated review by F1 in patients with no findings in the first review is limited.

ASPL-TFE3 Oncoprotein Regulates Cell Cycle Progression and Induces Cellular Senescence by Up-Regulating p21.

Alveolar soft part sarcoma is an extremely rare soft tissue sarcoma with poor prognosis. It is characterized by the unbalanced recurrent chromosomal translocation der(17)t(X;17)(p11;q25), resulting in the generation of an ASPL-TFE3 fusion gene. ASPL-TFE3 oncoprotein functions as an aberrant transcriptional factor and is considered to play a crucial role in the tumorigenesis of alveolar soft part sarcoma. However, the underlying molecular mechanisms are poorly understood. In this study, we identified p21 (p21WAF1/CIP1) as a direct transcriptional target of ASPL-TFE3. Ectopic ASPL-TFE3 expression in 293 cells resulted in cell cycle arrest and significant increases in protein and mRNA levels of p21. ASPL-TFE3 activated p21 expression in a p53-independent manner through direct transcriptional interactions with the p21 promoter region. When ASPL-TFE3 was expressed in human bone marrow-derived mesenchymal stem cells in a tetracycline-inducible manner, we observed the up-regulation of p21 expression and the induction of senescence-associated ß-galactosidase activity. Suppression of p21 significantly decreased the induction of ASPL-TFE3-mediated cellular senescence. Furthermore, ASPL-TFE3 expression in mesenchymal stem cells resulted in a significant up-regulation of proinflammatory cytokines associated with senescence-associated secretory phenotype (SASP). These results show that ASPL-TFE3 regulates cell cycle progression and induces cellular senescence by up-regulating p21 expression. In addition, our data suggest a potential mechanism by which ASPL-TFE3-induced senescence may play a role in tumorigenesis by inducing SASP, which could promote the protumorigenic microenvironment.

Unusual case of tacrolimus vascular toxicity after deceased donor renal transplantation.

We report a case of tacrolimus vascular toxicity found on a protocol biopsy shortly after a deceased donor renal transplantation. The patient was immunologically high-risk and acute antibody-mediated rejection during post-transplant dialysis phase was suspected on the protocol biopsy. Although the patient was stable after treatment of rejection, a further examination showed a very rare but specific side-effect of tacrolimus. It is sometimes difficult to make a differential diagnosis during postoperative dialysis period among AMR, primary non-functioning, drug toxicity, infection or just prolonged recovery from the damage of a long agonal phase on the non-heart beating donor. Although the possibilities of coexistence of rejection or other causes such as infection have not been completely excluded, it is important to be aware of this unusual side effect of tacrolimus.

Impact of serum ferritin level on hepatocarcinogenesis in chronic hepatitis C patients.

AIM: To elucidate the impact of the serum ferritin level, a surrogate indicator of hepatic iron accumulation, on hepatocarcinogenesis in chronic hepatitis C patients. METHODS: Serum ferritin was measured in 487 chronic hepatitis C patients without history of hepatocellular carcinoma (HCC) after excluding patients in phlebotomy, those with overt chronic gastrointestinal bleeding and those who achieved sustained virological response before enrollment. Patients were divided into four groups (G1-G4) by quartile points of serum ferritin, with sexes separated. RESULTS: The serum ferritin level was positively correlated with total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT), γ-glutamyltransferase, hemoglobin and AFP, and inversely correlated with prothrombin activity in both sexes. A significant difference in HCC incidence was observed only in male patients; the incidence was higher in G1 (≤80 ng/mL, n = 54) and G4 (≥323 ng/mL, n = 54) compared with that of G2 (81-160 ng/mL, n = 54) and G3 (161-322 ng/mL, n = 52). The spline curve indicating the relationship between the hazard ratio and serum ferritin level took the form of a J-shape for male patients. In multivariate analysis, G1 and G4 showed higher incidence of HCC among men with a hazard ratio of 2.19 (95% confidence interval, 1.02-4.70; P = 0.045) compared with G2 and G3, together with older age, lower serum albumin and ALT above the normal upper limit. CONCLUSION: The serum ferritin level is an independent risk factor for HCC development in male patients with chronic hepatitis C when the level is extremely high or low.

Biopsy findings on a stable recipient after secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation.

Using desensitization protocol, we performed a secondary donor specific antibody (DSA) positive and ABO incompatible kidney transplantation. One-hour biopsy showed no C4d deposition. The protocol biopsy after 2 weeks showed diffuse C4d deposition with peritubulitis. After 12 weeks, however, the protocol biopsy showed disappearance of tubulitis in spite of remaining C4d deposition. The recipient was in stable condition with excellent graft function despite high titer of the DSA. Monitoring of protocol biopsy is critical while antibody titer and the interpretation of the histological findings correlating with clinical markers must be considered.

Impact of fecal occult blood on obscure gastrointestinal bleeding: observational study.

AIM: To elucidate the association between small bowel diseases (SBDs) and positive fecal occult blood test (FOBT) in patients with obscure gastrointestinal bleeding (OGIB). METHODS: Between February 2008 and August 2013, 202 patients with OGIB who performed both capsule endoscopy (CE) and FOBT were enrolled (mean age; 63.6 ± 14.0 years, 118 males, 96 previous overt bleeding, 106 with occult bleeding). All patients underwent immunochemical FOBTs twice prior to CE. Three experienced endoscopists independently reviewed CE videos. All reviews and consensus meeting were conducted without any information on FOBT results. The prevalence of SBDs was compared between patients with positive and negative FOBT. RESULTS: CE revealed SBDs in 72 patients (36%). FOBT was positive in 100 patients (50%) and negative in 102 (50%). The prevalence of SBDs was significantly higher in patients with positive FOBT than those with negative FOBT (46% vs 25%, P = 0.002). In particular, among patients with occult OGIB, the prevalence of SBDs was higher in positive FOBT group than negative FOBT group (45% vs 18%, P = 0.002). On the other hand, among patients with previous overt OGIB, there was no significant difference in the prevalence of SBDs between positive and negative FOBT group (47% vs 33%, P = 0.18). In disease specific analysis among patients with occult OGIB, the prevalence of ulcer and tumor were higher in positive FOBT group than negative FOBT group. In multivariate analysis, only positive FOBT was a predictive factors of SBDs in patients with OGIB (OR = 2.5, 95%CI: 1.4-4.6, P = 0.003). Furthermore, the trend was evident among patients with occult OGIB who underwent FOBT on the same day or a day before CE. The prevalence of SBDs in positive vs negative FOBT group were 54% vs 13% in patients with occult OGIB who underwent FOBT on the same day or the day before CE (P = 0.001), while there was no significant difference between positive and negative FOBT group in those who underwent FOBT two or more days before CE (43% vs 25%, P = 0.20). CONCLUSION: The present study suggests that positive FOBT may be useful for predicting SBDs in patients with occult OGIB. Positive FOBT indicates higher likelihood of ulcers or tumors in patients with occult OGIB. Undergoing CE within a day after FOBT achieved a higher diagnostic yield for patients with occult OGIB.

Comparison of improved prognosis between hepatitis B- and hepatitis C-related hepatocellular carcinoma.

AIM: Treatment strategies for hepatocellular carcinoma (HCC) have been advanced. The aim of this study was to compare the change of the prognosis between hepatitis B-related HCC (B-HCC) and hepatitis C-related HCC (C-HCC) in the last two decades. METHODS: We enrolled 166 B-HCC patients who underwent percutaneous ablation between 1990 and 2009. Patients were divided into three groups according to the treatment time period: 1990-1995 (cohort 1, n = 19), 1996-2002 (cohort 2, n = 49) and 2003-2009 (cohort 3, n = 98). We enrolled 1219 C-HCC patients who underwent percutaneous ablation during the same period (n = 190, 413 and 616, respectively.). Interferon and nucleoside/nucleotide analog use was investigated. Prognosis was evaluated for each cohort using the Kaplan-Meier method and a multivariate Cox proportional hazard regression model. RESULTS: Two (11%), 24 (49%) and 80 (82%) B-HCC patients received nucleoside/nucleotide analogs during the follow-up period in cohorts 1-3, respectively. Among them 1, 18 and 62 patients achieved viral remission, respectively. Thirty-four (18%), 35 (8%) and 84 (14%) C-HCC patients received interferon therapy, respectively. The 5-year B-HCC (P < 0.001) survival rates were 52.6%, 61.1% and 81.6% for cohorts 1-3, respectively. However, the survival rates were 55.6%, 58.8% and 61.1% for C-HCC (P = 0.12), respectively. The B-HCC prognosis improved dramatically (P < 0.001) over time, whereas the prognosis of C-HCC improved moderately (P = 0.01). CONCLUSION: The prognosis of B-HCC has improved dramatically over time, whereas that of C-HCC has improved moderately.

Impact of serum levels of interleukin-6 and adiponectin on all-cause, liver-related, and liver-unrelated mortality in chronic hepatitis C patients.

BACKGROUND AND AIM: Various inflammatory cytokines and adipokines have been implicated in hepatitis C virus (HCV)-mediated liver disease, and interleukin-6 (IL-6) and adiponectin may play key roles. In addition, these factors may be associated with chronic hepatitis C (CHC)-induced extrahepatic manifestations. However, little data are available on the role of these factors on future outcomes of CHC patients. This study aims to evaluate the impact of serum levels of IL-6 and adiponectin on all-cause mortality, liver-related mortality, and liver-unrelated mortality. METHODS: A long-term follow-up study was conducted, consisting of 325 CHC patients, for which we previously reported positive associations between these factors (Serum levels of IL-6 and adiponectin) and hepatocellular carcinoma (HCC) development. RESULTS: During the follow-up period (mean, 13.0 year), there were 92 events consisting of 91 deaths (liver related, 72; liver unrelated, 19) and 1 liver transplantation due to liver failure. High IL-6 and adiponectin levels, defined as being higher than each median value at baseline, were associated with significantly higher incidences of not only HCC development but also all-cause mortality. Interestingly, high IL-6 was strongly associated with only liver-related mortality, whereas high-serum adiponectin was associated with not only liver-related, but also liver-unrelated mortality. Multivariate analysis identified high IL-6 as an independent risk factor for liver-related mortality and high adiponectin as an independent risk factor for liver-unrelated mortality. CONCLUSION: High serum levels of IL-6 and adiponectin were associated with higher all-cause and liver-related mortality in CHC patients. In addition, high adiponectin was associated with liver-unrelated mortality. The measurement of these factors may provide information useful for predicting future outcomes in CHC patients.

Slight elevation of high-sensitivity C-reactive protein to predict recurrence and survival in patients with early stage hepatitis C-related hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is associated with chronic inflammation derived from various origins. We investigated whether high-sensitivity C-reactive protein (hsCRP) could predict recurrence and survival after curative treatment for early stage hepatitis C virus-related HCC (C-HCC). METHODS: We enrolled 387 patients with three or fewer C-HCC nodules, none of which exceeded 3 cm, and of Child-Pugh class A or B who underwent radiofrequency ablation. We divided the patients into high and low hsCRP groups based on the optimal cut-off value for recurrence using a split-sample method and maximally selected rank statistics. Differences in recurrence and survival rates were evaluated by the Kaplan-Meier method and the log-rank test. Hazard ratios of hsCRP were adjusted with confounding factors using a multiple Cox regression model. We also assessed the correlations between hsCRP levels and clinical parameters. RESULTS: The optimal hsCRP cut-off value was 0.08 mg/dL. The cumulative recurrence rates after 5 years in the high and low hsCRP groups were 90.0% and 82.2%, respectively (P = 0.028), and the corresponding survival rates were 50.9% and 71.8%, respectively (P < 0.001). Higher hsCRP was an independent predictor for recurrence (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 1.03-1.67; P = 0.026) and survival (aHR, 1.59; 95% CI, 1.14-2.22; P = 0.007). hsCRP was correlated with central obesity as well as tumor burden and liver dysfunction. CONCLUSION: Slight elevation of the hsCRP level, even within the normal range, can predict recurrence and survival after curative treatment among patients with early stage C-HCC.

Tumor markers are more useful in patients undergoing surveillance for hepatocellular carcinoma with unreliable results by ultrasonography.

AIM: The objectives of this study was to evaluate the utility of tumor markers in hepatocellular carcinoma (HCC) surveillance based on the reliability of ultrasonography. METHODS: We analyzed 313 patients with HCC detected through a surveillance program using ultrasonography combined with three tumor markers from February 2000 to December 2010. The patients were categorized into two groups based on the triggering event: the US group (n = 281) in which a tumor was first detected using ultrasonography and the TM group (n = 32) in which elevated tumor markers led to the diagnosis of a tumor that was undetected using ultrasonography. The reliability of ultrasonography was scored on a 4-point scale based on three items (coarseness of liver parenchyma, patient obesity and liver atrophy). Additionally, patient survival was assessed using the Kaplan-Meier method and log-rank test. RESULTS: The median tumor size was 20 mm (interquartile range, 15-24). The reliability of ultrasonography was evaluated as good in 208 (66.5%), satisfactory in 80 (8.0%), poor in 21 (6.7%) and unsatisfactory in four (1.2%) patients. The proportion of patients in the TM group increased significantly according to the score, from 7.2% to 25.0% (P = 0.01). The survival rates of patients at 3 and 5 years were 83.7% and 57.2% in the US group, and 79.3% and 59.4% in the TM group, respectively (P = 0.98). CONCLUSION: Tumor markers may play a diagnostic role in patients with unreliable ultrasonography results. The survival of patients diagnosed by elevated tumor markers was not significantly different from those diagnosed by ultrasonography.

Frequency of and predictive factors for vascular invasion after radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: Vascular invasion in patients with hepatocellular carcinoma (HCC) is representative of advanced disease with an extremely poor prognosis. The detailed course of its development has not been fully elucidated. METHODS: We enrolled 1057 consecutive patients with HCC who had been treated with curative intent by radiofrequency ablation (RFA) as an initial therapy from 1999 to 2008 at our department. We analyzed the incidence rate of and predictive factors for vascular invasion. The survival rate after detection of vascular invasion was also analyzed. RESULTS: During a mean follow-up period of 4.5 years, 6075 nodules including primary and recurrent lesions were treated by RFA. Vascular invasion was observed in 97 patients. The rate of vascular invasion associated with site of original RFA procedure was 0.66% on a nodule basis. The incidence rates of vascular invasion on a patient basis at 1, 3, and 5 years were 1.1%, 5.9%, and 10.4%, respectively. Univariate analysis revealed that tumor size, tumor number, alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein were significant risk predictors of vascular invasion. In multivariate analysis, DCP was the most significant predictor for vascular invasion (compared with a DCP of ≤100 mAu/mL, the hazard ratio was 1.95 when DCP was 101-200 mAu/mL and 3.22 when DCP was >200 mAu/mL). The median survival time after development of vascular invasion was only 6 months. CONCLUSION: Vascular invasion occurs during the clinical course of patients initially treated with curative intent. High-risk patients may be identified using tumor markers.

Cause-specific mortality associated with aging in patients with hepatocellular carcinoma undergoing percutaneous radiofrequency ablation.

OBJECTIVE: The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients. MATERIALS AND METHODS: We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as 'younger' and those at least 75 as 'elderly'. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan-Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model. RESULTS: Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child-Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death. CONCLUSION: RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.

Increased serum autotaxin levels in hepatocellular carcinoma patients were caused by background liver fibrosis but not by carcinoma.

BACKGROUND: Controversy exists as to whether autotaxin (ATX) may be importantly associated with pathophysiology of hepatocellular carcinoma (HCC). METHODS: We evaluated serum ATX levels and its mRNA expression in consecutive 148 HCC patients treated with radiofrequency ablation (RFA) and 30 patients with hepatic resection. RESULTS: Although increased serum ATX levels were observed in almost all the patients treated with RFA, they were not reduced after RFA. Furthermore, serum ATX levels were associated not with tumor burden but with the parameters predicting for liver fibrosis, such as liver stiffness values. Then, in surgically-treated patients, there was no significant correlation between serum ATX levels and ATX mRNA expression levels in HCC tissues. Notably, ATX mRNA expression levels in HCC tissues were not higher than those in peri-tumorous tissues. Finally, serum ATX levels in surgically-treated HCC patients were rather correlated with ATX mRNA expression levels in peri-tumorous tissues as well as with liver fibrosis stage. CONCLUSION: The increase in serum ATX levels in HCC patients may not be caused by abundant ATX production in HCC tissues but by fibrosis in the background livers.

Incidence of malignancies in patients with IgG4-related disease.

OBJECTIVE: It has been discussed whether IgG4-related disease (IgG4-RD), including autoimmune pancreatitis (AIP), is associated with malignancy; however, the issue has not been clarified. METHODS: We analyzed 113 patients with IgG4-RD in whom malignancy was not diagnosed at the time of IgG4-RD onset and the follow-up period was longer than six months. A total of 95 patients had AIP. The mean follow-up period was 73 months. The incidence of the observed malignancies was compared with the expected incidence in an age- and sex-matched general Japanese population based on the Vital Statistics of Japan. RESULTS: There were 15 malignancies (lung cancer in five patients, pancreatic cancer in two patients, gastric cancer in two patients, bile duct cancer in one patient, renal cancer in one patient, breast cancer in one patient, tongue cancer in one patient, malignant melanoma in one patient and acute myeloid leukemia in one patient) in 14 patients during the follow-up period. The calculated standardized incidence rate of the total malignancies was not significant, that is, 1.04 (95% CI 0.57-1.75). CONCLUSION: The incidence of total malignancies in IgG4-RD patients is similar to that observed in the general population. At present, it is reasonable to conclude that IgG4-RD is not associated with an increased incidence of total malignancies.

Thermal influence of radiofrequency ablation for bone: an experimental study in normal rabbit bone.

OBJECTIVE: To evaluate the heat effects of radiofrequency ablation (RFA) on normal bone by mechanical testing, MRI, and histology. MATERIALS AND METHODS: The institutional animal care and use committee approved the animal study. Thirty-two adult Japanese white rabbits were included in our study. Bone biopsy needles were inserted from the distal end of the right (RFA side) and the left (control side) femurs using a fluoroscopic guide. A 17-gauge internally cooled RFA electrode with a 2-cm active tip was inserted through the needle to the right femur, and RFA was performed for 12 min using a 200-W generator. Animals were divided into four groups and 8 animals from each group were euthanized on day 1, day 7, day 30, and day 60 after RFA. MRI was performed prior to euthanasia. Three-point bending test was performed to measure flexural strength. Student's t test was used to evaluate for significant differences between RFA and control side for each group. Femurs underwent histological examination by hematoxylin and eosin staining after the bending test. RESULTS: MRI showed a high-intensity rim around the bone on T2WI. Three-point bending test showed no statistically significant differences (P < 0.05) between the RFA and the control side in any of the groups. Histologically, osteocytes of cortical bone showed cell death, but the lamellar structure was preserved in all groups and bone remodeling was observed. CONCLUSION: Heat by RFA did not change normal bone strength within 2 months, despite the heat effects in the cortical bone and cell death.