Incidental detection of localized prostate cancer with low PSA by computed tomography scan: A report of two cases.

Serum prostate-specific antigen (PSA) levels play an important role in the screening and diagnosis of prostate cancer (PCa). The recommended PSA cut-off in PCa screening is 4 ng/ml. We report two cases of localized PCa with low PSA levels that were incidentally found by computed tomography (CT) performed for another disease.

Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis.

The dextran sodium sulfate (DSS)-induced colitis mouse model has been widely utilized for human colitis research. While its mechanism involves a response to double-strand deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (Atm)-checkpoint kinase 2 (Chk2) pathway activation related to such response remains unreported. Recently, we reported that cyclin D1-binding protein 1 (Ccndbp1) activates the pathway reflecting DNA damage in its knockout mice. Thus, this study aimed to examine the contribution of Ccndbp1 and the Atm-Chk2 pathway in DSS-induced colitis. We assessed the effect of DSS-induced colitis on colon length, disease activity index, and histological score and on the Atm-Chk2 pathway and the subsequent apoptosis in Ccndbp1-knockout mice. DSS-induced colitis showed distal colon-dominant Atm and Chk2 phosphorylation, increase in TdT-mediated dUTP-biotin nick end labeling and cleaved caspase 3-positive cells, and histological score increase, causing disease activity index elevation and colon length shortening. These changes were significantly ameliorated in Ccndbp1-knockout mice. In conclusion, Ccndbp1 contributed to Atm-Chk2 pathway activation in the DSS-induced colitis mouse model, causing inflammation and apoptosis of mucosal cells in the colon.

Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM-CHK2 Pathway.

Cyclin D1 binding protein 1 (CCNDBP1) is considered a tumor suppressor, and when expressed in tumor cells, CCNDBP1 can contribute to the viability of cancer cells by rescuing these cells from chemotherapy-induced DNA damage. Therefore, this study focused on investigating the function of CCNDBP1, which is directly related to the survival of cancer cells by escaping DNA damage and chemoresistance. Hepatocellular carcinoma (HCC) cells and tissues obtained from Ccndbp1 knockout mice were used for the in vitro and in vivo examination of the molecular mechanisms of CCNDBP1 associated with the recovery of cells from DNA damage. Subsequently, gene and protein expression changes associated with the upregulation, downregulation, and irradiation of CCNDBP1 were assessed. The overexpression of CCNDBP1 in HCC cells stimulated cell growth and showed resistance to X-ray-induced DNA damage. Gene expression analysis of CCNDBP1-overexpressed cells and Ccndbp1 knockout mice revealed that Ccndbp1 activated the Atm-Chk2 pathway through the inhibition of Ezh2 expression, accounting for resistance to DNA damage. Our study demonstrated that by inhibiting EZH2, CCNDBP1 contributed to the activation of the ATM-CHK2 pathway to alleviate DNA damage, leading to chemoresistance.

Septicemic listeriosis during adalimumab- and golimumab-based treatment for ulcerative colitis: case presentation and literature review.

Listeria monocytogenes is a common bacterium that can trigger an episode of amphixenosis from the consumption of contaminated food. It survives in the host as an intracellular parasite and can get reactivated when the host's immune system is compromised. The use of anti-tumor necrosis factor-α (TNF-α) blockers is reported to increase the risk of L. monocytogenes infections. In the field of gastroenterology, the use of TNF-α blockers is on the rise due to remarkable efficacy in select patients with inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease and the rise in the incidence and prevalence of IBDs. There are few case reports on this topic, despite the rapid development of novel TNF-α blockers. Here, we report two cases of septicemic listeriosis encountered during treatment with the more recent TNF-α blockers, namely, adalimumab and golimumab, in ulcerative colitis and review the published literature on the topic.

Usefulness of chemokine C-C receptor 7- /programmed cell death-1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis.

AIM: A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis. METHODS: Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry. RESULTS: The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores. CONCLUSIONS: The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

Hemorrhagic Gastric Metastasis from Hepatocellular Carcinoma Successfully Treated Using Coil Embolization of the Left Gastric Artery.

A 62-year-old man initially underwent transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma (HCC). One year after the initial treatment, he developed anemia. Upper gastrointestinal endoscopy revealed irregularly elevated tumors in the lower anterior gastric body, which were diagnosed to be metastasis from HCC. Left gastric artery coil embolization was performed to prevent sustained bleeding, and his anemia partially improved. In addition to direct invasion, hematogenous metastasis to the stomach from HCC is possible and therefore should be considered during treatment. Transcatheter arterial embolization for gastric metastasis is an effective treatment method which achieves a good degree of hemostasis in patients without any surgical indications.

Eosinophilic esophagitis after total gastrectomy treated with proton pump inhibitors: a case report.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder in the esophagus characterized by symptoms related to esophageal dysfunction and eosinophil-predominant inflammation. EoE and Gastro Esophageal Reflux Disease (GERD) are known not to be mutually exclusive and share a complex relationship. Proton pump inhibitors (PPIs), which are generally used in the treatment of GERD, could be used to treat esophageal eosinophilia in suspected EoE. We report a rare case of EoE after total gastrectomy that responded to PPIs. Our case indicates that the onset of EoE does not necessarily require an acid reflux-induced antigen-mediated drive, and the action of PPIs in patients with active EoE is unrelated to gastric acid suppression.

Cone beam versus conventional computed tomography angiography volume measurement in partial splenic embolization.

When performing partial splenic arterial embolization (PSE), it can be difficult to determine the embolization ratio based on 2-dimensional digital subtraction angiography (DSA) image diagnosis alone. Therefore, at our department, we conduct computed tomography (CT) imaging intraoperatively and postoperatively to determine whether the planned embolization has been achieved. In recent years, developments in interventional radiology devices have enabled diagnostic imaging using cone beam CT. Here, we investigated whether the embolization ratio could be predicted from volume measurement with cone beam CT in PSE.We investigated correlations between volume measurement with conventional CT angiography (CTA) and volume measurement with cone beam CTA in 11 cases that underwent PSE with cone beam CT guidance (Allura Clarity FD20; Phillips, Amsterdam, The Netherlands) between December 2013 and May 2018.The mean subject age was 65.0 ± 5.8 years (6 men, 5 women). The subjects had underlying liver disorders of hepatitis C virus infection (4 cases), nonalcoholic steatohepatitis (4 cases), and alcohol-related disease (3 cases). A positive correlation was noted between conventional CTA and cone beam CTA, with infarction rates of 61.28 ±â€Š9.31% and 64.04 ±â€Š9.24%, respectively. The correlation coefficient between the 2 variables was .772.Because blood washout occurs rapidly in the spleen, contrast medium had to be continuously injected during imaging to enable dual-phase imaging with cone beam CT. However, we successfully performed imaging up to the second phase and volume measurement for the embolization ratio by inserting a catheter into the splenic artery and confirming the cone beam CT arrival time from the DSA images. The results were almost identical to those obtained from volume measurement with conventional CT based on CTA imaging. Thus, our results suggest that the splenic embolization ratio measurement obtained via cone beam CTA can be used to assess PSE treatment endpoints.

Efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation in patients with recurrent hepatocellular carcinoma and thrombocytopenia.

AIMS: Thrombocytopenia is often associated with chronic liver disease. Lusutrombopag is a small molecule thrombopoietin receptor agonist designed to temporarily increase the platelet count in patients with chronic liver disease for whom elective invasive procedures are planned. In the present study, the efficacy and safety of repeated use of lusutrombopag prior to radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma were examined. METHODS: Eight patients with hepatocellular carcinoma who had a platelet count <50 000/µL prior to both initial and repeat RFA at the time of recurrence received lusutrombopag (3 mg/day) orally for 7 days between March 2016 and August 2018. The following were compared: the effect of lusutrombopag to increase the platelet count as determined by the platelet count after the initial and repeated use of lusutrombopag, the rate of avoiding platelet transfusion, and the presence of any complications. RESULTS: The platelet count increased to 103 100 ± 22 800/µL 14 days after the first treatment and to 110 700 ± 17 800/µL 14 days after the repeated use. None of the patients required platelet transfusion. None of the patients developed clinical symptoms such as thrombosis, fever, rash, portal vein thrombosis, bleeding, or any other serious adverse events. CONCLUSIONS: Repeated use of lusutrombopag increased the platelet count. It did not cause any serious adverse events and led to avoidance of platelet transfusion. Radiofrequency ablation was carried out safely in all patients. Future studies with more cases of repeated use are needed to examine the long-term efficacy and safety of lusutrombopag.

Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.

Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.

Telaprevir-based triple therapy following partial splenic arterial embolization for chronic hepatitis C with thrombocytopenia can reduce carcinogenesis and improve hepatic function reserve.

Thrombocytopenia in patients with chronic hepatitis C negatively impacts interferon (IFN)-based treatment. The aim of this study was to evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy including IFN for patients who have undergone partial splenic arterial embolization (PSE). Ten patients with thrombocytopenia who were infected with hepatitis C virus (HCV) genotype 1b received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN)α2b and ribavirin following PSE. A sustained virological response (SVR) was seen in 9 of the 10 patients who could be assessed. Early relapse was seen in 1 patient who had the IL-28B minor allele and a null response to pretreatment. The α-fetoprotein levels of the patients decreased from 17.94±7.30 ng/ml prior to PSE to 4.33±2.41 ng/ml at 6 months after triple therapy (P=0.08). Furthermore, serum albumin levels improved significantly from 3.68±0.49 g/dl pre-PSE to 4.13±0.34 g/dl at 12 months after triple therapy (P=0.043). PSE contributed to the treatment success of triple therapy, particularly for patients who were either treatment-naïve, had a history of relapse or the IL28B major allele. This strategy can reduce carcinogenesis and improve hepatic function reserve.

Concurrent partial splenic embolization with transcatheter arterial chemoembolization for hepatocellular carcinoma can maintain hepatic functional reserve.

AIM: Hepatocellular carcinoma (HCC) is frequently complicated with cirrhosis, and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism. Partial splenic embolization (PSE) has been performed for thrombocytopenia resulting from hypersplenism. We studied the efficacy in terms of hepatic functional reserve and safety in patients who underwent concurrent transcatheter arterial chemoembolization (TACE) with PSE for HCC. METHODS: The study population consisted of 101 HCC patients with thrombocytopenia. Fifty-three patients were treated with concurrent TACE/PSE (PSE group), and the remaining 48 TACE patients without PSE (non-PSE group) were investigated hepatic functional reserve. RESULTS: Platelet counts were significantly higher in the PSE group after 2 weeks, 2 months and 6 months after TACE than the non-PSE group. Child-Pugh score significantly deteriorated from 7.13 ± 1.16 to 7.60 ± 1.20 at 2 weeks, to 7.71 ± 1.25 at 2 months, and 7.71 ± 1.35 at 6 weeks after TACE in the non-PSE group. Hence, it worsened from 7.04 ± 1.05 to 7.21 ± 0.99 at 2 weeks temporally, but improved to 7.00 ± 1.17 after 2 months and 6.70 ± 1.16 at 6 weeks after TACE in the PSE group. CONCLUSION: Thrombocytopenia has been improved and treatment continued using concurrent PSE. In addition, hepatic functional reserve could be maintained even after treatment for HCC. Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain hepatic reserve, and may contribute to improving the prognosis of HCC.

Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant recurrence and survival for early hepatocellular carcinoma.

BACKGROUND/AIMS: The Child-Pugh classification system is the most widely used system for assessing hepatic functional reserve in HCC treatment. In the Child-Pugh classification system, serum albumin levels are used to accurately assess the status of protein metabolism and nutrition. To date, a lack of attention has been given to amino acid metabolism. In the present study, we investigated whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of amino acid metabolism can serve as both a prognostic factor for early HCC and a predictive factor for recurrence. METHODOLOGY: We conducted a cohort study of 50 patients with stage I/II HCC enrolled between May 2002 and December 2010. It was investigated whether BTR can serve as both a prognostic factor and a predictive factor for HCC recurrence. RESULTS: Overall survival rates were significantly higher in patients with high baseline BTR than in those with low BTR. Multivariate analysis showed that both BTR and serum albumin were prognostic factors, and that BTR was the best predictive factor for recurrence. CONCLUSIONS: BTR was a prognostic factor for early HCC and the most predictive factor for intrahepatic distant recurrence and contributing factors for survival.

Prevalence of Howell-Jolly bodies caused by partial splenic embolization for portal hypertension.

OBJECTIVE: Postsplenectomy sepsis (PSS) and overwhelming postsplenectomy infection (OPSI) following splenectomy or the development of hyposplenism are associated with a high mortality rate. The presence of Howell-Jolly bodies (HJBs) in peripheral erythrocytes is attracting attention as a parameter of hyposplenism. To date, whether HJBs appear following partial splenic embolization (PSE) has not been investigated. Therefore, we examined the prevalence of HJBs in patients who have undergone PSE. METHODS: Whether HJBs were present in 95 patients who underwent PSE between November 2007 and August 2012 was assessed. RESULTS: No serious complications occurred due to PSE; however, 17 of the 95 patients (17.89%) exhibited HJBs during the follow-up. The residual spleen volume and splenic infarction rate did not differ significantly compared to those observed in the HJB-negative group. CONCLUSION: With the recent increase in the use of autoanalyzers, the opportunities to perform microscopic examinations have been decreasing. Therefore, the presence of HJBs, which can only be confirmed visually, may be overlooked, and the clinical significance of these bodies tends to be disregarded. However, the presence of HJBs is associated with a risk of PSS and OPSI due to hyposplenism. Because HJBs are common in the peripheral erythrocytes of patients who have undergone PSE, irrespective of the residual spleen volume or splenic infarction rate, the presence or absence of HJBs should be assessed visually. In HJB-positive patients, preventing serious infections, for example, by administering the pneumococcal vaccine, is important.

Radiofrequency ablation during continuous saline infusion can extend ablation margins.

AIM: To determine whether fluid injection during radiofrequency ablation (RFA) can increase the coagulation area. METHODS: Bovine liver (1-2 kg) was placed on an aluminum tray with a return electrode affixed to the base, and the liver was punctured by an expandable electrode. During RFA, 5% glucose; 50% glucose; or saline fluid was infused continuously at a rate of 1.0 mL/min through the infusion line connected to the infusion port. The area and volume of the thermocoagulated region of bovine liver were determined after RFA. The Joule heat generated was determined from the temporal change in output during the RFA experiment. RESULTS: No liquid infusion was 17.3 ± 1.6 mL, similar to the volume of a 3-cm diameter sphere (14.1 mL). Mean thermocoagulated volume was significantly larger with continuous infusion of saline (29.3 ± 3.3 mL) than with 5% glucose (21.4 ± 2.2 mL), 50% glucose (16.5 ± 0.9 mL) or no liquid infusion (17.3 ± 1.6 mL). The ablated volume for RFA with saline was approximately 1.7-times greater than for RFA with no liquid infusion, representing a significant difference between these two conditions. Total Joule heat generated during RFA was highest with saline, and lowest with 50% glucose. CONCLUSION: RFA with continuous saline infusion achieves a large ablation zone, and may help inhibit local recurrence by obtaining sufficient ablation margins. RFA during continuous saline infusion can extend ablation margins, and may be prevent local recurrence.