Tomohiro Minami

Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma

Background and Aims: Patients with intermediate-stage hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE) are considered to be candidates for sorafenib. The aim of this study was to evaluate the superiority of conversion of treatment to sorafenib on overall survival (OS) for cases refractory to TACE. Methods: This was a retrospective cohort study carried out on 497 patients with HCC who were treated with TACE therapy at our hospital between January 2008 and December 2013. Fifty-six patients were diagnosed as refractory to TACE during their clinical course and they were divided into two cohorts, (1) those who switched from TACE to sorafenib and (2) those who continued TACE. The overall survival (OS) after the time of being refractory to TACE was evaluated between the two groups. Results: After refractoriness to TACE therapy was confirmed, 24 patients continued with TACE (TACE-group) and 32 patients underwent treatment conversion to sorafenib (sorafenib-group). The median OS was 24.7 months in the sorafenib-group and 13.6 months in the TACE-group (p=0.002). Conclusions: Conversion to sorafenib significantly improves the OS in patients refractory to TACE therapy with intermediate-stage HCC. Administration of sorafenib is therefore recommended in such circumstances of TACE treatment failure.

Combination guidance of contrast-enhanced US and fusion imaging in radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on contrast-enhanced US/fusion imaging.

Purpose: The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging. Materials and Methods: We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance. Results: The average number of treatment sessions was 1.1 (range: 1-2) in the CEUS guidance group, 1.1 (range: 1-2) in the fusion imaging guidance group, and 1.1 (range: 1-3) in the combination of CEUS and fusion imaging guidance group. Treatment analysis did not reveal significantly more RFA treatment sessions in the combination guidance group than in the other groups (p = 0.97, Students t test). During the follow-up period (1.1-85.3 months, mean ± SD, 43.2 ± 59.5), the 3-year local tumor progression rates were 4.9, 7.2, and 5.9% in the CEUS guidance group, the fusion imaging guidance group, and the combination guidance group, respectively (p = 0.84, log-rank test). Conclusion: In spite of selection bias, session frequency and local tumor progression were not different under the combination guidance with CEUS and fusion imaging in RFA. The combination of fusion imaging and CEUS guidance in RFA therapy is an effective treatment for HCC with poor conspicuity on B-mode US and CEUS/fusion imaging.

Validation of a Modified Substaging System (Kinki Criteria) for Patients with Intermediate-Stage Hepatocellular Carcinoma

Introduction: Barcelona Clinic Liver Cancer (BCLC) stage B, an intermediate stage, includes various conditions of hepatocellular carcinoma (HCC). This heterogeneity of the patients with intermediate-stage HCC makes it difficult to predict their survival rates. In the present study, we examined the validity of the modified Bolondi classification (Kinki criteria) as a subclassification of patients with BCLC stage B HCC. Methods: Of 906 patients who underwent conventional transarterial chemoembolization at Kinki University Hospital, 753, who met the inclusion criteria, were examined. Of these 753 patients, 425 (56.4%) with BCLC stage B were subclassified using the Kinki criteria to examine the survival rate. Results: According to the Kinki criteria, 158 (37.2%) were subclassified into subclass B1, 236 (55.5%) into B2, and 31 (7.3%) into B3. The comparison of the survival rates showed that the median overall survival was 3.9 years (95% CI, 3.2-4.6) in the BCLC subclass B1 group, 2.5 years (95% CI, 2.2-3.1) in the B2 group, and 1.1 years (95% CI, 0.6-1.5) in the B3 group (p < 0.001). Conclusion: When the BCLC stage B patients were subclassified according to the Kinki criteria, survival curves were stratified with significant differences, suggesting that the Kinki criteria were suitable for the subclassification of the intermediate-stage HCC patients.

Ultrasound Elastography Correlates Treatment Response by Antiviral Therapy in Patients with Chronic Hepatitis C

Objective: To investigate the relationship between tissue elasticity before and after antiviral therapy and shear wave as well as strain elastography. Methods: FibroScan and real-time tissue elastography were performed before and after antiviral therapy for chronic hepatitis C, and treatment efficacy and elastographic findings were comparatively analyzed. Elasticity was evaluated by measuring liver stiffness (LS) in kilopascals using FibroScan, and the liver fibrosis index (LFI) was assessed by real-time tissue elastography. Results: LS and LFI correlated well before and after therapy (r = 0.567, p = 0.003 and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LS increased in 4 of 5 patients. Patients with an increase in both LS and LFI were all in the non-SVR group (3/3, 100%). In addition, LS increased in all patients except 1 in the non-SVR group (4/5, 80%). In the SVR group, both LS and LFI decreased in all patients except 1 (18/19, 94.7%). In the patient with an increase in LS despite achieving SVR, LS decreased quickly after alcohol cessation. Conclusions: With a few exceptions, SVR improved LS. All patients with an increase in LFI were in the non-SVR group, even though LFI decreased in 2 patients. Our findings suggest that an LFI increase indicates lack of treatment efficacy with antiviral therapy. LFI may be useful for the assessment of treatment efficacy in patients with worsening of LS despite achieving SVR with antiviral therapy.

Outcome of Combination Therapy with Sofosbuvir and Ledipasvir for Chronic Type C Liver Disease

Introduction: Recently, the treatment of chronic hepatitis C has markedly advanced. A phase III clinical study of combination therapy with sofosbuvir (SOF) and ledipasvir (LDV) was conducted in Japan, and the additive therapeutic effects were reported. In this study, we report the results of treatment in our hospital. Methods: Of 147 patients with chronic type C liver disease who had consulted our hospital since September 2015 and received SOF/LDV therapy, in 91 subjects a sustained virological response of 12 weeks (SVR12) could be evaluated. Results: In all 91 patients, end treatment response was achieved. Subsequently, recrudescence was noted in 1 before the completion of treatment (week 12); an SVR12 was achieved in 90 patients (99%). The following adverse reactions were observed in 3 patients (3.3%): bradycardia, paroxysmal atrial fibrillation, and heart failure with QT prolongation, which were associated with heart disease. Conclusion: A favorable SVR was achieved by SOF/LDV therapy even in elderly patients, those with liver cirrhosis, or those having undergone radical treatment of liver cancer. Furthermore, a high tolerance was demonstrated, but adverse reactions associated with the heart may appear in patients with heart disease as an underlying disease; strict management during treatment is necessary.

Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis.

Objective: Refractory ascites reduces the quality of life of liver cirrhosis patients. Albumin preparation and diuretics, such as furosemide, have been used to treat refractory ascites, but the effect was poor in many patients. In this study, we analyzed patients treated with tolvaptan (TLV) at our hospital and investigated predictors of the effect. Methods: The subjects were 70 patients for whom TLV was introduced to treat refractory ascites who could be analyzed between November 2013 and March 2015 at our hospital. Patient background before initiation of oral TLV treatment, the dose of diuretics, and each item of biochemical tests of blood and urine were investigated, and factors correlated with the treatment effect were analyzed. An increase of ≥1,000 ml in the daily urine volume from the day before oral treatment or a decrease of ≥1 kg in the body weight within 7 days as an early effect was observed in 33 patients and not observed in 37 patients. TLV treatment was continued for 60 days or longer in 12 of the 37 patients in whom no early effect was observed, and the presence or absence of a delayed effect and predictors of the effect were investigated. A decrease in ascites on abdominal CT with improvement of subjective symptoms at 60 days was defined as a delayed effect. Results: When early predictors of the effect were investigated by univariate analysis, serum blood urea nitrogen (BUN) and serum creatinine (Cr) were significantly higher in the non-responder group (BUN: p = 0.03, Cr: p = 0.04), but no factor independently associated with the treatment effect was extracted on multivariate analysis. The delayed effect was noted in 4 (33.3%) of the 12 patients, but no predictor of the effect before treatment was identified. However, reactions, such as an increase in serum Na and reduction of urinary osmotic pressure, were observed early after TLV administration in some patients in whom the delayed effect was observed. Conclusions: The diuretic effect of TLV may decrease in renal hypofunction patients. Since the delayed effect was noted in a specific ratio of patients, continuation of TLV administration is an option even though the early treatment effect is poor unless ascites aggravates or adverse effects develop.

Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience

Objective: To investigate whether balloon-occluded transcatheter arterial chemoembolization (b-TACE) can produce a more dense accumulation of iodized oil in various stages of hepatocellular carcinoma (HCC), from single to uncountable, to overcome inferior local control. Materials and Methods: We studied 27 patients with HCC, including single to uncountable multiple lesions, who underwent b-TACE between August 2013 and April 2015. Dynamic CT was performed at baseline and 1-3 months after b-TACE. The treatment effect (TE) after b-TACE was evaluated using the Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan. Results: In the countable HCC group, contrast-enhanced CT demonstrated RECICL TE4 in 43.8% (14/32), TE3 in 12.5% (4/32), TE2 in 37.5% (12/32), and TE1 in 6.3% (2/32) of patients. For the TACE-naïve cohort, the objective response rate was 52.9%. The objective response rate was 60% for the previously TACE-treated cohort. In the uncountable multiple HCC group, the objective response rate was 0% (0/10), with progressive disease in 90% (9/10) of patients. Conclusion: Our observations suggested that b-TACE did not reduce the efficacy of retreatment for HCC with an insufficient outcome from conventional TACE, but it could not improve the efficacy of treatment for uncountable multiple HCCs.

Evaluation of ART Scores for Repeated Transarterial Chemoembolization in Japanese Patients with Hepatocellular Carcinoma

Objective: Transarterial chemoembolization (TACE) is recommended as a first-line therapy for hepatocellular carcinoma (HCC) patients ineligible for curative therapy and without portal invasion. The Assessment for Retreatment with TACE (ART) scoring system was recently proposed for identifying patients who would not show sufficient survival benefit from repeated TACE. We reevaluated the performance of ART in HCC patients treated in Japan, where selective TACE is commonly used. Methods: Between 2000 and 2013, 988 patients with HCC underwent TACE at Kinki University Hospital, and 627 received ≥2 sessions of TACE. Seventy-six patients who underwent ≥2 TACE sessions within 90 days were investigated for their performance of the ART score in the context of overall survival (OS). Results: Only 12% (76/627) of patients underwent ≥2 TACE sessions within 90 days. Of those, 52 patients showed a low ART score (0-1.5), and 24 had a high ART score (≥2.5); the median OS was 20.2 and 37.6 months, respectively (p = 0.8207). Conclusion: The ART scoring system did not demonstrate a sufficiently predictive impact on OS among the patients who underwent ≥2 TACE sessions within 90 days. Application of the ART score should be carefully considered because differences in TACE procedures and post-TACE treatment can affect the results while evaluating OS.

US-US Fusion Imaging in Radiofrequency Ablation for Liver Metastases

Objective: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. Methods: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1). The maximal diameter of the tumors ranged from 0.8 to 4.0 cm (mean ± SD 1.6 ± 0.9 cm). Results: The mean number of electrode insertions was 1.6 per session (range 1-3). Technically, effective ablation was achieved in a single session in all patients, and safety ablative margins were confirmed on contrast-enhanced CT for early assessment of tumor response. There were no serious adverse events or procedure-related complications. During the follow-up period (median 220 days, range 31-417 days), none of the patients showed local tumor progression. Conclusion: US-US fusion imaging could show the tumor images before ablation and the ablative area on US in real time. The image overlay of US-US fusion imaging made it possible to evaluate the ablative margin three dimensionally according to the US probe action. Therefore, US-US fusion imaging can contribute to RFA therapy with a safety margin, that is, the so-called precise RFA.

Computer-Aided Diagnosis Based on Convolutional Neural Network System for Colorectal Polyp Classification: Preliminary Experience

Background and Aim: Computer-aided diagnosis (CAD) is becoming a next-generation tool for the diagnosis of human disease. CAD for colon polyps has been suggested as a particularly useful tool for trainee colonoscopists, as the use of a CAD system avoids the complications associated with endoscopic resections. In addition to conventional CAD, a convolutional neural network (CNN) system utilizing artificial intelligence (AI) has been developing rapidly over the past 5 years. We attempted to generate a unique CNN-CAD system with an AI function that studied endoscopic images extracted from movies obtained with colonoscopes used in routine examinations. Here, we report our preliminary results of this novel CNN-CAD system for the diagnosis of colon polyps. Methods: A total of 1,200 images from cases of colonoscopy performed between January 2010 and December 2016 at Kindai University Hospital were used. These images were extracted from the video of actual endoscopic examinations. Additional video images from 10 cases of unlearned processes were retrospectively assessed in a pilot study. They were simply diagnosed as either an adenomatous or nonadenomatous polyp. Results: The number of images used by AI to learn to distinguish adenomatous from nonadenomatous was 1,200:600. These images were extracted from the videos of actual endoscopic examinations. The size of each image was adjusted to 256 × 256 pixels. A 10-hold cross-validation was carried out. The accuracy of the 10-hold cross-validation is 0.751, where the accuracy is the ratio of the number of correct answers over the number of all the answers produced by the CNN. The decisions by the CNN were correct in 7 of 10 cases. Conclusion: A CNN-CAD system using routine colonoscopy might be useful for the rapid diagnosis of colorectal polyp classification. Further prospective studies in an in vivo setting are required to confirm the effectiveness of a CNN-CAD system in routine colonoscopy.