Takatomo Sano

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

IntroductionPancreatic 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 methodsHIFU 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.ResultsResults 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.ConclusionHIFU therapy may have the possibility of becoming one of the combination therapies for treating pancreatic carcinoma in the future.

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.

Relationship between the Status of Blood Supply in the Non-hypervascularHepatocellular Nodules among Chronic Liver Diseases and the HypervascularChange

Objectives: We observed the time-course changes of blood flow in non-hypervascular hepatocellular nodules that showed hypointensity in the hepatobiliary phase on Gd-EOB-DTPA-enhanced magnetic resonance imaging (EOB-MRI), and evaluated the relationship between hypervascular change and the status of blood supply in the nodules. Methods: The study included 69 hepatocellular nodules in 33 patients demonstrating hypointensity in the hepatobiliary phase on EOB-MRI and showing non-hypervascular features on CT during hepatic arteriography (CTHA) performed during the same period. Results: In relation to blood flow on CTHA/ CT during arterial portography (CTAP), the cumulative rate of hypervascular change at 52 weeks was 0.0% for iso/iso, 29.7% for hypo/iso, 61.5% for iso/hypo, and 55.0% for hypo/hypo. Multivariate analysis using COX proportional hazards regression showed that CTAP findings (hypodensity) and CTHA findings (hypo-density) were significant variables for hypervascular change. Conclusions: In cases of non-hypervascular hepatocellular tumors, nodules with decreased arterial or portal blood flow that show hypointensity in the hepatobiliary phase on EOB-MRI are likely to develop into typical hepatocellular carcinoma in a shorter time.

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

IntroductionIrreversible 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 descriptionIn 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 evaluationAt 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.ConclusionIt 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.

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.

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

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).

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

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.

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

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.

P0250 : Effect of irreversible electroporation (IRE) on the porcine liver: comparison with radiofrequency ablation

Background and Aims: Irreversible electroporation (IRE) is a promising, non-thermal ablation therapy for hepatocellular carcinoma, which, unlike radiofrequency thermal ablation (RFA), induces apoptosis through irreversible formation of nanoscale pores in the cell membrane with delivery of high-voltage electric current and is considered to improve safety in the vicinity of heat-sensitive blood vessel and bile duct. The aim of the present study is to clarify the acute pathological effect of IRE on the liver and also to compare with effect of RFA. Methods: Three pigs underwent ultrasound-guided IRE and RFA of normal liver under general anesthesia and at laparotomy. A total of 9 IRE ablated areas and 3 RFA ablated areas were created. We examined histopathologic findings of ablated areas at 4 hours after therapy with immunohistochemical methods. The pathologic findings according to IRE ablation conditions were compared with findings of RFA. Results: In IRE zones, various degree of congestion and hemorrhage, apoptotic change of hepatocytes, defluxion of portal endothelial cells and cholangitis were observed in hepatic lobules. With the increase in the total pulse number of IRE delivered, these pathological findings became remarkable. NADPH-diaphorase enzyme histochemistry performed in IRE zones demonstrated the stainability is very weak in the hepatic lobule, which reflecting defluxion of hepatocytes and reduced activity of viable hepatocytes in acute phase, while the stainability is lost in the central portion of RFA. Silver impregnation stain and collagen type 4 immunohistochemistry showed that reticular fibers and collagen fibers around the sinusoid remain well-preserved in IRE zones, on the other hand, those in RFA zones are very poorly stained. The vessels in IRE zones demonstrated a relatively intact configuration of positive smooth muscle cells for Caldesmon staining and endothelial cells for Factor 8 staining, with the minimal endothelial damage, while the vessels in RFA zones demonstrated a negative or weakened reaction. Bile duct epithelial cells showed a positive reaction for cytokeratin 7 staining in IRE zones with desquamated cells, while an entirely negative reaction in RFA zones, revealing protein denaturation. Conclusions: Unlike RFA, IRE induces apoptosis of hepatocytes, endothelium of the blood vessels and mucosal membrane of the bile ducts, whereas preservation of sinusoidal framework and vascular structure may have the potential for liver regeneration.

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.