Dual red imaging (novel advanced endoscopy) can increase visibility and can predict the depth in diagnosing esophageal varices.

BACKGROUND: Dual red imaging (DRI) is a new technology that can increase the visibility of deeper veins compared with narrow band imaging (NBI). As esophageal varices (EVs) are a vascular disease occurring in the submucosal layer, their visibility might be increased by DRI. We prospectively clarified whether the visibility of EVs with red color sign (RCS) can be increased by DRI, and clarified the relation between the visibility scores and the obtained endoscopic ultrasound (EUS) images. METHODS: Forty patients were enrolled. The visibility of the EVs on DRI and NBI endoscopic images was evaluated by five observers in a blinded manner and was compared with a white light image (bad, 0; equal, 1; good, 2). The diameter of the lumen and the depth of the EVs and RCS from the epithelium were measured by EUS. The relation between the visibility scores and the EUS findings was investigated. RESULTS: The DRI scores were 1.66 ± 0.34 for the EV substance and 1.79 ± 0.28 for the RCS, whereas the NBI scores were 0.68 ± 0.38 and 0.41 ± 0.28, respectively. A significant negative correlation was found between the depth and the visibility score (r = -0.505, p = 0.001 for EVs; r = -0.458, p = 0.003 for RCS). CONCLUSIONS: DRI increased the visibility of the EVs and RCS. The visibility of the EVs or RCS in the shallower position was more enhanced by DRI. Visual recognition of the changing degrees of visibility by DRI enables the prediction of the depth of EVs.

Optimal injection rate of ultrasound contrast agent for evaluation of focal liver lesions using an automatic power injector: a pilot study.

OBJECTIVE: To determine the optimal bolus injection rate of ultrasound (US) contrast agent in vascular imaging for focal liver lesions. METHODS: Thirteen patients with 13 focal liver lesions (5 hepatocellular carcinomas (HCCs) with cirrhosis, 4 liver metastases, 2 hemangiomas, 1 intrahepatic cholangiocarcinoma, 1 focal nodular hyperplasia) received two bolus injections of Sonazoid (at 0.5 and 2.0 mL/s) using an automatic power injector. The lesion-to-liver contrast ratio at peak enhancement was quantitatively evaluated. Enhancement of the lesions compared to liver parenchyma was assessed by two independent readers using a five-point scale and qualitatively evaluated by receiver operating characteristic (ROC) analysis. RESULTS: For all lesions, the contrast ratio was not significantly different between the two injection rates. For HCCs, the contrast ratio was higher at 0.5 mL/s (7.41 ± 6.56) than at 2.0 mL/s (4.28 ± 4.66, p = 0.025). For all lesions, the mean area under the ROC curve (AUC) was not significantly different between the two injection rates. For HCCs, the AUC was greater at 0.5 mL/s than at 2.0 mL/s (AUC: 0.86, p = 0.013). CONCLUSION: In contrast-enhanced US, an injection rate of 0.5 mL/s is superior to an injection rate of 2.0 mL/s for the quantitative and qualitative analysis of HCCs in the cirrhotic liver.

Branched-chain amino acid-enriched nutrient increases blood platelet count in patients after endoscopic injection sclerotherapy.

AIM: Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated. METHODS: A total of 61 LC patients were randomly divided into an EIS monotherapy group (non-BCAA group, n = 31) and an EIS combined with BCAA therapy group (n = 30). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points. RESULTS: The platelet counts before treatment were at the same level in both groups (P = 0.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P = 0.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P < 0.01). The skeletal muscle volume measured by InBody720 significantly decreased in the non-BCAA group (P < 0.001). CONCLUSION: EIS induced protein-energy malnutrition, however, skeletal muscle volume was maintained by taking BCAA. Administration of BCAA had some effect in maintaining the nutritional state, and may improve the platelet count. Taking a greater amount of nutrients and shorter dietary restriction period or hospitalization was desirable.

Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non-alcoholic steatohepatitis.

PURPOSE: The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. METHODS: Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. RESULTS: Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). CONCLUSIONS: Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

The close linkage between the elasticity modulus measured by real-time mapping shear wave elastography and the presence of hepatocellular carcinoma in patients with a sustained virological response to interferon for chronic hepatitis C.

PURPOSE: Some patients develop hepatocellular carcinoma (HCC) after sustained virological response (SVR) to interferon therapy for chronic hepatitis C (CH-C). The aim of this study was to examine the linkage between liver elasticity and the presence/absence of HCC in patients after SVR. METHODS: We enrolled 42 patients who underwent real-time mapping shear wave elastography (SWE) after SVR to interferon therapy for CH-C. Of the 42 patients, six had HCC and 36 did not. We retrospectively compared the elasticity modulus and other clinical parameters between patients with and without HCC. RESULTS: Elasticity modulus measured by SWE, age, and serum albumin was significantly different between patients with and without HCC. Age, Fibrosis-4 index, serum gamma-globulin, total protein, and albumin levels were significantly correlated with the elasticity modulus. Areas under receiver operating characteristic curves of elasticity modulus, gamma-globulin, and age for the presence of HCC were 0.963, 0.888, and 0.778, respectively. In patients with an elasticity modulus ≥6.5 kPa, both sensitivity and specificity for the presence of HCC were 83.3 %. CONCLUSION: The study demonstrated the close linkage between the elasticity modulus measured by SWE and the presence of HCC in patients after SVR.

Irreversible electroporation for nonthermal tumor ablation in patients with hepatocellular carcinoma: initial clinical experience in Japan.

PURPOSE: This clinical study was conducted to evaluate the safety and short-term outcomes of irreversible electroporation (IRE) for the treatment of patients with hepatocellular carcinoma (HCC) in Japan. MATERIALS AND METHODS: The study was designed in a prospective setting. Five patients (3 men and 2 women; mean age, 66.6 ± 5.8 years) with 6 HCCs were enrolled and treated using percutaneous ultrasound (US)-guided IRE. Safety was assessed based on adverse events and laboratory values. Local control was assessed using contrast-enhanced US with a perflubutane microbubble contrast agent, contrast-enhanced multiphase CT, and gadoxetic acid-enhanced MRI (EOB-MRI) at designated points. RESULTS: The tumors ranged in diameter from 11 to 28 mm (mean diameter, 17.5 ± 6.3 mm). Five of the 6 tumors (83 %) were successfully treated, with no local recurrence to date (mean follow-up 244 ± 55 days). In 1 lesion located in liver segment 1, residual tumor was diagnosed at 7 days after intervention by follow-up EOB-MRI. No serious complications related to the IRE procedure were observed. CONCLUSION: The results of this study suggest that image-guided percutaneous IRE can achieve satisfactory local disease control, particularly for small HCCs, and is well tolerated by patients.

Case study to assess the safety of irreversible electroporation near the heart.

INTRODUCTION: Irreversible electroporation (IRE) is a promising technique for the focal treatment of soft tissue tumors. Even though the local application of an excessive electric field is a potential cause of cardiac arrhythmias, initial clinical studies have shown that IRE is generally safe when cardiac gating is employed. CASE DESCRIPTION: In this case report, we observed an episode of ventricular extrasystoles without hemodynamic changes during which time the synchronization device failed to operate properly, with pulses delivered not in the absolute refractory period but in the relative refractory period. DISCUSSION AND EVALUATION: At present, persons performing IRE must keep in mind that there is a small but real risk of synchronization failure even when a cardiac synchronization device is used. CONCLUSION: It is advisable to err on the side of caution when treating lesions near the heart.

Restoration of natural killer cell activity by pegylated interferon-alpha/ribavirin therapy in chronic hepatitis C patient.

AIM: The combination therapy of pegylated interferon-α and ribavirin (PEG IFN/RBV) is one of the effective treatments for chronic hepatitis C (CHC) patients. Natural killer (NK)-cell activity was reported to be impaired in patients with hepatitis C virus (HCV). The aim of this study was to examine whether PEG IFN/RBV therapy could restore NK activity in CHC patients. METHODS: In 19 CHC patients, PEG IFN/RBV therapy was performed. Just before (0M), at 3 months of the therapy (3M) and at 6 months after completion of the therapy (6M), NK activity and the frequency of NK cells, CD56(dim) NK cells and CD56(bright) NK cells in peripheral blood was estimated by creatinine release assay and flow cytometry. Statistical analysis was performed by anova and Mann-Whitney U-test. RESULTS: anova showed that NK activity significantly improved at 6M (vs 0M, P < 0.05) in the patients studied and in the patients with sustained virological response (SVR). It also showed that frequency of CD56(bright) NK cells was significantly increased at 6M (vs 0M, P < 0.05) in the patients studied and in the SVR group. However, no significant change in NK activity and frequency of CD56(bright) NK cells were detected in non-SVR group. Furthermore, NK activity ratio (6M/0M) in the SVR group was revealed to be higher compared with that in the non-SVR group by analysis using Mann-Whitney U-test (P < 0.05). CONCLUSION: PEG IFN/RBV therapy in CHC patients could improve NK activity by increasing the frequency of CD56(bright) NK cells in SVR patients. Our study also revealed that eradication of HCV could restore NK-cell activity.

Recent progress in radiofrequency ablation therapy for hepatocellular carcinoma.

In order to attain better ablation and more effective management of hepatocellular carcinoma (HCC), new approaches and devices in radiofrequency ablation (RFA) therapy were presented and discussed in a workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan. A novel bipolar RFA apparatus was introduced in Japan in January 2013. Hundreds of subjects with HCC were treated with multipolar RFA with varied devices and plans. Among these, no-touch ablation was one of the most useful procedures in the treatment of HCC with the apparatus. In RFA therapy, a few assisting devices and techniques were applied for convenience and improvement of the thermal ablation procedure. Contrast-enhanced ultrasonography and three-dimensional fusion imaging technique using volume data of CT or MRI could improve exact targeting and shorten the treatment time for RFA procedures under ultrasonographic guidance. A more complicated method using a workstation was also reported as being helpful in planning the ablated shape and volume in multineedle RFA. The effective use of sedatives and antianalgesics as well as a novel microwave apparatus with a cooled-tip electrode was also discussed.

Safety trial of high-intensity focused ultrasound therapy for pancreatic cancer.

AIM: To evaluate the safety and clinical application of high-intensity focused ultrasound (HIFU) therapy for unresectable pancreatic cancer (PC). METHODS: Thirty PC patients (16 cases in stage III and 14 cases in stage IV) with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy. Informed consent was obtained. This study began at the end of 2008 and was approved by the ethics committee of our hospital [Institutional Review Board (IRB): 890]. The HIFU device used was the FEP-BY02 (Yuande Bio-Medical Engineering, Beijing, China). RESULTS: The mean tumor size after HIFU therapy changed to 30.9 ± 1.7 mm from 31.7 ± 1.7 mm at pre-therapy. There were no significant changes in tumor size, mean number of treatment sessions (2.7 ± 0.1 mm), or mean total treatment time (2.4 ± 0.1 h). The rate of symptom relief effect was 66.7%. The effectiveness of primary lesion treatment was as follows: complete response, 0; partial response, 4; stable disease, 22; progressive disease, 4. Treatment after HIFU therapy included 2 operations, 24 chemotherapy treatments, and 4 best supportive care treatments. Adverse events occurred in 10% of cases, namely pseudocyst formation in 2 cases and mild pancreatitis development in 1. However, no severe adverse events occurred in this study. CONCLUSION: We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

Obliteration of gastric varices improves the arrival time of ultrasound contrast agents in hepatic artery and vein.

BACKGROUND AND AIM: Liver cirrhosis (LC) is accompanied by hepatic arterializations, intrahepatic shunts, and hyperdynamic circulations. These changes shorten the arrival time (AT) of ultrasound contrast agents to the hepatic vein (HV). Whether treatment of gastric fundal varices (GVs) by balloon-occluded transvenous obliteration (B-RTO) improves the AT in LC patients was prospectively investigated. METHODS: A total of 32 LC patients with GVs and 10 normal controls (NCs) were enrolled. This study was approved by the clinical research ethics committee. Images of hepatic artery (HA), portal vein (PV), and HV were monitored after an injection of a contrast agent using quantification software. The AT before and after B-RTO in LC patients and that in NCs were compared. RESULTS: All GVs were treated effectively, and indocyanine green retention rate was improved (P < 0.0001). The mean values of the HA, PV, and HV ATs in the NCs were 21.9 ± 3.3, 28.2 ± 2.0, and 40.5 ± 2.1 s, respectively. Those in LC patients were 17.4 ± 4.4, 21.9 ± 5.6, and 26.3 ± 6.7, respectively, which were shorter than those in NCs (P < 0.01, P < 0.002, P < 0.0001, respectively). However, these ATs were significantly prolonged 1 week after B-RTO, with mean values of 18.7 ± 4.8, 23.8 ± 6.0, and 30.0 ± 7.2 s (P = 0.043, P < 0.01, P < 0.001). CONCLUSION: Obliteration of GVs shifted the AT in LC patients to the normalization, raising the possibility of improvement of arterialization and intrahepatic shunt.

Usefulness of transnasal argon plasma coagulation for esophageal varices compared with the peroral method: a randomized and prospective clinical study.

BACKGROUND: Argon plasma coagulation (APC) is very useful as a consolidation treatment for reducing the recurrence of esophageal varices (EVs). However, repeated sedation in endoscopic treatment has the risk of prolonging hepatic encephalopathy and affects the respiratory state of liver cirrhosis (LC) patients, in whom pulmonary arteriovenous shunts are observed. We evaluated prospectively whether transnasal endoscopic APC without sedation is more effective than peroral endoscopic APC with sedation. PATIENTS AND METHODS: LC patients (n = 101), treated by endoscopic injection sclerotherapy to eradicate EVs, were randomly divided into a transnasal APC group (n = 50) and a peroral APC group (n = 51). The primary efficacy endpoint was the cumulative recurrence rate of EVs. The secondary endpoints were blood pressure (BP), heart rate, oxygen saturation during APC and complications. RESULTS: There was no significant difference in the cumulative recurrence rate of EVs at 36 months between the transnasal APC and peroral APC groups (35.0 vs. 40.8%, p = 0.39, log-rank test), indicating that transnasal APC is not inferior to peroral APC. The transnasal APC group showed more stable intraoperative BP and oxygen saturation values, and a lower incidence of epigastralgia (56.0 vs. 74.5%, p = 0.04). CONCLUSION: The efficacy of reducing the recurrence of EVs in the transnasal APC group was not significantly different from that in the peroral APC group. Transnasal APC caused less distress and required no sedation. Therefore, this method was more advantageous for LC patients at risk of suffering from prolongation of hepatic encephalopathy.

Noninvasive diagnostic method for idiopathic portal hypertension based on measurements of liver and spleen stiffness by ARFI elastography.

BACKGROUND: Acoustic radiation force impulse (ARFI) elastography is an ultrasound technique that is capable of measuring tissue stiffness noninvasively. It is difficult to differentiate idiopathic portal hypertension (IPH) from liver cirrhosis (LC) or chronic hepatitis (CH), and liver biopsy is essential. We investigated whether it would be possible to noninvasively diagnose IPH by measuring the stiffness of the liver and spleen by ARFI. METHODS: The subjects were 17 IPH patients, 25 LC patients, 20 CH patients, and 20 normal controls (NC). We measured liver stiffness, spleen stiffness, and the spleen/liver stiffness ratio, and plotted ROC curves. RESULTS: The median value of liver stiffness in the IPH group was lower than that in the LC group (p = 0.00077) and about the same as in the CH group (p = 0.79). The median value of spleen stiffness was highest in the IPH group (IPH vs. LC group, p = 0.003; IPH vs. CH group, p < 0.00001). The spleen/liver stiffness ratio was lower in the LC group and in the CH group, and higher in the IPH group (p < 0.001, respectively). When an ROC curve of spleen/liver stiffness ratios was plotted to differentiate between the IPH group and the combined group of patients with other liver diseases (LC + CH group), when a cutoff value of 1.71 was used, the AUROC was 0.933 sensitivity 0.941, specificity 0.800, and accuracy 0.839. CONCLUSION: Measuring the spleen/liver stiffness ratio by ARFI made it possible to noninvasively, specifically, and accurately diagnose IPH.

Flexible imaging color enhancement improves visibility of transnasal endoscopic images in diagnosing esophageal varices: a multicenter prospective blinded study.

OBJECTIVE: To clarify the usefulness of transnasal esophagogastroduodenoscope (N-EGD) with all flexible imaging color enhancement (FICE) patterns (0-9) for the diagnosis of esophageal varices (EV). METHODS: A total of 50 patients with EV were examined during the same period by N-EGD without sedation and by peroral endoscopy (O-EGD) with sedation. The visibility of treatment scars, microvessels, recurrent EV and red color sign (RCS) were measured. Visibility was evaluated by five blinded observers (poor-good: 0-10), and the effect of both endoscopic examinations on the cardiorespiratory function of the patients was measured. RESULTS: The image scores for O-EGD and N-EGD with ordinary mode and N-EGD with FICE were 7.3 ± 1.2, 6.1 ± 1.0 and 6.9 ± 1.0 for treatment scars; 7.2 ± 1.4, 6.2 ± 1.2 and 7.3 ± 1.0 for microvessels; 7.2 ± 1.2, 6.1 ± 1.0 and 7.1 ± 1.0 for recurrent EV and 7.2 ± 1.3, 6.1 ± 1.3, and 7.2 ± 1.2 for RCS, respectively (intraclass correlation coefficients > 0.6). When FICE patterns 2, 6 and 9 were used, visibility was much improved. Ten minutes after insertion, the double product values in the N-EGD with the FICE group were significantly better (P < 0.05). CONCLUSIONS: N-EGD with FICE is very useful for the diagnosis of EV and can improve the visibility of N-EGD on each lesion to the same level as that of O-EGD. N-EGD with FICE does not require sedation and may reduce the risk of hepatic encephalopathy.

The current potential of high-intensity focused ultrasound for pancreatic carcinoma.

INTRODUCTION: Pancreatic carcinoma has one of the poorest prognoses among malignant tumors. Many pancreatic carcinoma patients who undergo common treatments, such as surgery, radio-chemotherapy and chemotherapy, gained little benefit because of the histological characteristics. MATERIALS AND METHODS: HIFU is a new technique of noninvasive treatment for unresectable pancreatic carcinoma. HIFU has the ability to ablate the deep tissues inside body from an external source using high-intensity focused ultrasound. The effects of HIFU can result in cell destruction and tissue necrosis. RESULTS: Results from study in China in 251 patients with advanced pancreatic carcinoma suggested that HIFU treatment could reduce the size of tumors without causing complications and prolong survival. Moreover, according to some reports from China, HIFU treatment is suggested to be useful as the one of palliative treatments for unresectable pancreatic carcinoma. Our case of HIFU therapy for pancreatic carcinoma is presented including pathological findings in this paper. The results suggested that HIFU treatment might be effective in controlling local tumor. CONCLUSION: HIFU therapy may have the possibility of becoming one of the combination therapies for treating pancreatic carcinoma in the future.