Impact of age on sorafenib outcomes in hepatocellular carcinoma: an international cohort study.

BACKGROUND: There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. METHODS: In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. RESULTS: Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93-1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2-4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. CONCLUSIONS: Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.

Gankyrin induces STAT3 activation in tumor microenvironment and sorafenib resistance in hepatocellular carcinoma.

Most hepatocellular carcinomas (HCC) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumorigenesis in the colon. Although the in vitro function of gankyrin is well known, its role in vivo remains to be elucidated. We investigated the effect of gankyrin in the tumor microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrinf/f ) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrinf/f ). Gankyrin upregulates vascular endothelial growth factor expression in tumor cells. Gankyrin binds to Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), mainly expressed in liver non-parenchymal cells, resulting in phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). Gankyrin deficiency in non-parenchymal cells, but not in parenchymal cells, reduced STAT3 activity, interleukin (IL)-6 production, and cancer stem cell marker (Bmi1 and epithelial cell adhesion molecule [EpCAM]) expression, leading to attenuated tumorigenic potential. Chronic inflammation enhances gankyrin expression in the human liver. Gankyrin expression in the tumor microenvironment is negatively correlated with progression-free survival in patients undergoing sorafenib treatment for HCC. Thus, gankyrin appears to play a critical oncogenic function in tumor microenvironment and may be a potential target for developing therapeutic and preventive strategies against HCC.

The ALBI grade provides objective hepatic reserve estimation across each BCLC stage of hepatocellular carcinoma.

BACKGROUND & AIMS: Overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC) due to the mutual influence of cirrhosis and active malignancy in dictating patient's mortality. The ALBI grade is a recently described index of liver dysfunction in hepatocellular carcinoma, based solely on albumin and bilirubin levels. Whilst accurate, this score lacks cross-validation, especially in intermediate stage HCC, where OS is highly heterogeneous. METHODS: We evaluated the prognostic accuracy of the ALBI grade in estimating OS in a large, multi-centre study of 2426 patients, including a large proportion of intermediate stage patients treated with chemoembolization (n=1461) accrued from Europe, the United States and Asia. RESULTS: Analysis of survival by primary treatment modality confirmed the ALBI grade as a significant predictor of patient OS after surgical resection (p<0.001), transarterial chemoembolization (p<0.001) and sorafenib (p<0.001). Stratification by Barcelona Clinic Liver Cancer stage confirmed the independent prognostic value of the ALBI across the diverse stages of the disease, geographical regions of origin and time of recruitment to the study (p<0.001). CONCLUSIONS: In this large, multi-centre retrospective study, the ALBI grade satisfied the criteria for accuracy and reproducibility following statistical validation in Eastern and Western HCC patients, including those treated with chemoembolization. Consideration should be given to the ALBI grade as a stratifying biomarker of liver reserve in routine clinical practice. LAY SUMMARY: Liver failure is a key determinant influencing the natural history of hepatocellular carcinoma (HCC). In this large multi-centre study we externally validate a novel biomarker of liver functional reserve, the ALBI grade, across all the stages of HCC.

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2).

The multikinase inhibitor sorafenib is the first oral molecular targeted agent with proven prognostic benefit in unresectable advanced hepatocellular carcinoma (HCC). However, as with other drugs, sorafenib has its limitations, and various clinical trials have been conducted to develop novel molecular targeted agents for use alone or in combination with existing locoregional therapies. Despite this, clinical trials of molecular targeted agents combined with transarterial chemoembolization (TACE) have not reported major treatment outcomes to date. In this review, we describe previous clinical trials of combination therapy with TACE and a molecular targeted agent in patients with unresectable HCC.

Prophylactic Suturing Closure Is Recommended after Endoscopic Treatment of Colorectal Tumors in Patients with Antiplatelet/Anticoagulant Therapy.

The prophylactic closure of mucosal defects after endoscopic resection is known to prevent postoperative bleeding in colorectal lesions. However, closure of large mucosal defects is difficult with conventional clips only, and several closure techniques have been previously described; use of an Endoloop, 8-ring loop, or loop clip and a small incision around the mucosal defect. Given that the prophylactic closure requires much cost and time, the application should be limited to high-risk cases. Medication of antithrombotics or antiplatelet agents would be one of the reasonable indications for prophylactic closure of mucosal defects after endoscopic resection of colorectal tumors.

Influence of Liver Inflammation on Liver Stiffness Measurement in Patients with Autoimmune Hepatitis Evaluation by Combinational Elastography.

OBJECTIVE: In order to evaluate the influence of liver inflammation on liver stiffness measurement (LSM) by the simultaneous use of shear wave and strain imaging (combinational elastography), shear wave and strain imaging were compared before and after initial therapy for autoimmune hepatitis (AIH). METHODS: Nine AIH patients initially treated with steroid were enrolled. Transient elastography and real-time tissue elastography were performed just before and 1 month after the start of initial steroid treatment. Blood samples, LSM, and the liver fibrosis index (LFI) were compared. RESULTS: Aspartate aminotransferase (p = 0.002) and alanine aminotransferase (ALT) (p = 0.015) were significantly decreased after initial treatment. The LSM was 15.5 ± 9.6 kPa at baseline, decreasing to 7.2 ± 2.3 kPa after initial treatment p = 0.034). The LFI was 1.67 ± 0.67 at baseline and 1.61 ± 0.66 after initial treatment; no significant change in LFI was recognized (p = 0.842). Between ΔALT and ΔLSM, a significant regression equation could be calculated as follows: ΔALT = -0.55 + 0.654 × ΔLSM. CONCLUSIONS: Combinational elastography was useful in evaluating not only the degree of liver fibrosis, but also the degree of liver inflammation in AIH.

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.

Characterization of Pancreatic Tumors with Quantitative Perfusion Analysis in Contrast-Enhanced Harmonic Endoscopic Ultrasonography.

OBJECTIVES: This study evaluated whether quantitative perfusion analysis with contrast-enhanced harmonic (CH) endoscopic ultrasonography (EUS) characterizes pancreatic tumors, and compared the hemodynamic parameters used to diagnose pancreatic carcinoma. METHODS: CH-EUS data from pancreatic tumors of 76 patients were retrospectively analyzed. Time-intensity curves (TIC) were generated to depict changes in signal intensity over time, and 6 parameters were assessed: baseline intensity, peak intensity, time to peak, intensity gain, intensity at 60 s (I60), and reduction rate. These parameters were compared between pancreatic carcinomas (n = 41), inflammatory pseudotumors (n = 14), pancreatic neuroendocrine tumors (n = 14), and other tumors (n = 7). All 6 TIC parameters and subjective analysis for diagnosing pancreatic carcinoma were compared. RESULTS: Values of peak intensity and I60 were significantly lower and time to peak was significantly longer in the groups with pancreatic carcinomas than in the other 3 tumor groups (p < 0.05). Reduction rate was significantly higher in pancreatic carcinomas than in pancreatic neuroendocrine tumors (p < 0.05). Areas under the receiver-operating characteristic curves for the diagnosis of pancreatic carcinoma using subjective analysis, baseline intensity, peak intensity, intensity gain, I60, time to peak, and reduction rate, were 0.817, 0.664, 0.810, 0.751, 0.845, 0.777, and 0.725, respectively. I60 was the most accurate parameter for differentiating pancreatic carcinomas from the other groups, giving values of sensitivity/specificity of 92.7/68.6% when optimal cutoffs were chosen. CONCLUSIONS: In pancreatic carcinomas, TIC patterns were markedly different from the other tumor types, with I60 being the most accurate diagnostic parameter. Quantitative perfusion analysis is useful for differentiating pancreatic carcinomas from other pancreatic tumors.

Risk Factors for Postoperative Bleeding in Endoscopic Submucosal Dissection of Colorectal Tumors.

BACKGROUND: Colonoscopic removal of adenomatous polyps or early cancer prevents death from colorectal cancer. Endoscopic submucosal dissection (ESD), which enables endoscopists to perform en bloc resection of flat or depressed colorectal tumors >20 mm, has recently been introduced and become a standard procedure in Japan. Although postoperative bleeding (POB) is a major complication associated with ESD, risk factors for POB have not been fully identified. METHODS: A total of 451 patients (509 lesions) who underwent colorectal ESD were retrospectively analyzed to identify clinical parameters associated with POB. RESULTS: POB occurred in 14 patients, and 7 of them had received antithrombotic therapy before ESD. Uni- and multivariate analyses revealed that antithrombotic therapy and rectal tumor location were strongly associated with POB following colorectal ESD. The incidence of POB was higher in patients on heparin bridge therapy (HBT) for the replacement of antithrombotic therapy than in patients with no HBT. Four of 7 patients (57.1%) on antithrombotic therapy experienced POB from the rectal lesions. CONCLUSION: Antithrombotic therapy and rectal lesions result in a higher POB incidence after colorectal ESD.

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.

Magnifying Narrow Band Imaging (NBI) for the Diagnosis of Localized Colorectal Lesions Using the Japan NBI Expert Team (JNET) Classification.

OBJECTIVE: The Japan NBI Expert Team (JNET) proposed a new narrow band imaging (NBI) classification system for colorectal tumors in June 2014. In this classification system, types 1, 2A, 2B, and 3 correspond to hyperplastic polyps (HPs) including sessile serrated polyps (SSPs), low-grade dysplasia (LGD), high-grade dysplasia (HGD) to shallow submucosal invasive (SM-s) carcinomas, and deep submucosal invasive (SM-d) carcinomas, respectively. METHODS: To validate this system, we performed a retrospective image evaluation study, in which 199 colorectal tumors previously assessed by NBI magnifying endoscopy were classified by 3 blinded experienced colonoscopists using the JNET system. The results were compared with the final pathological diagnoses to determine the JNET classification's accuracy. The interobserver agreement was calculated, and the intraobserver agreement was assessed after 6 months. RESULTS: The final pathological diagnoses identified 14 HPs/SSPs, 127 LGDs, 22 HGDs, 19 SM-s carcinomas, and 17 SM-d carcinomas. The respective sensitivities, specificities, positive predictive value, negative predictive value, and accuracies were as follows: Type 1, 85.7, 99.5, 92.3, 98.9, and 98.5%; Type 2A, 96.0, 81.9, 90.3, 92.1, and 90.9%; Type 2B, 75.6%, 90.5, 67.3, 93.4, and 87.4%; and Type 3, 29.4%, 100, 100, 93.8, and 94.0%. The interobserver agreement and the intraobserver agreement were moderate (κ value: 0.52) and excellent (κ value: 0.88), respectively. Lesions presenting as Type 2B during NBI comprised a range of colorectal tumors, including HGDs, SM-s, and SM-d. CONCLUSIONS: The JNET classification was useful for the diagnosis of HPs/SSPs, LGDs, and SM-d, but not SM-s lesions. For low-confidence cases, magnified chromoendoscopy is recommended to ensure correct diagnoses.

Clinical Analysis of Esophageal Stricture in Patients Treated with Intralesional Triamcinolone Injection after Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely used in the resection of superficial esophageal cancers. Since its use has been extended to cases involving large esophageal tumors occupying nearly the whole or the whole circumference of the lumen, the occurrence of esophageal stricture has increased. Although endoscopic injection of triamcinolone (TA) is widely used for the prevention of postoperative stricture, a significant number of patients still develop stricture after TA injection therapy. METHODS: We performed a retrospective study to identify the clinical parameters that predispose post-ESD patients to esophageal stricture after TA injection therapy. RESULTS: A total of 207 patients who were diagnosed with superficial esophageal cancer and subsequently underwent ESD were enrolled in this study. Among these patients, 53 patients and 57 lesions bearing mucosal defects covering greater than two-thirds of the esophageal circumference after ESD were treated with TA injection therapy. The rate of esophageal stricture was found to be highest in cases involving mucosal defects that covered more than seven-eighths of the circumference. CONCLUSION: Endoscopic TA injection is not sufficient for preventing esophageal stricture in patients bearing mucosal defects covering more than seven-eighths of the esophageal circumference after ESD.

Contrast-Enhanced Tissue Harmonic Imaging versus Phase Inversion Harmonic Sonographic Imaging for the Delineation of Hepatocellular Carcinomas.

OBJECTIVE: To compare contrast tissue harmonic imaging (THI) with low mechanical index (MI) and conventional contrast harmonic imaging (CHI) with respect to lesion visibility of hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-five patients (84 men and 41 women, age range 39-94 years, mean age 74 years) with 100 naïve HCCs and 30 lesions after radiofrequency ablation (RFA) for HCC were evaluated. One hundred and four patients had liver cirrhosis of Child-Pugh class A, and the remaining 21 had Child-Pugh class B cirrhosis. The lesion conspicuity and intratumoral echogenicity during the postvascular phase were compared using conventional CHI and contrast THI with low MI. RESULTS: The MI values ranged from 0.20 to 0.30 on conventional CHI and from 0.30 to 0.35 on contrast THI. Regarding HCC lesion conspicuity, contrast THI with low MI was clearer in 79 lesions (60.8%), equal in 34 lesions (26.2%), and less clear in 17 lesions (13.1%) when compared with conventional CHI. The lesion conspicuity with contrast THI was significantly better than that with conventional CHI (p < 0.01). All of the postablative lesions were well delineated in patients who received RFA. CONCLUSION: Low-MI contrast THI was superior to conventional CHI with respect to lesion visibility of HCCs and might offer good imaging for the guiding of RFA.

Malignant Transformation of Hepatocellular Adenoma.

The patient was a 20-year-old male in whom a hepatic hypervascular mass accompanied by intratumoral hemorrhage was detected on examination for epigastric pain. Based on the enlargement of the mass and diagnostic imaging, hepatocellular adenoma (HCA) was suspected and hepatectomy was performed. The lesion was diagnosed as malignant transformation of ß-catenin-activated HCA. There are only few reports of cases with malignant transformation of HCA in Japan; it is necessary to accumulate cases to investigate it.

Hepatocarcinogenesis Is Associated with Serum Albumin Levels after Sustained Virological Responses with Interferon-Based Therapy in Patients with Hepatitis C.

OBJECTIVE: It is a generally accepted fact that eradication of hepatitis virus C inhibits the subsequent development of hepatocellular carcinoma (HCC). On the contrary, a significant population of patients developed HCC despite sustained virological responses (SVRs) to interferon (IFN) therapy. METHODS: A total of 415 patients with chronic hepatitis C, who were treated at our hospital between 2004 and 2014, were enrolled for this study. We examined the risk factors for HCC development after IFN therapy. RESULTS: After analyzing various clinical parameters, it was concluded that a serum albumin (ALB) level <4.0 g/dL and the presence or absence of SVR achievement were risk factors for the development of HCC. When analyzing pre- and posttreatment factors, only a serum ALB level <4.0 g/dL was considered a significant risk factor. The presence or absence of liver fibrosis progression was not identified as a risk factor. CONCLUSIONS: In patients with a serum ALB level <4.0 g/dL before IFN therapy, hepatic carcinogenesis after SVR achievement need to be considered. Furthermore, the serum ALB level may be more useful than the degree of fibrosis for the prediction of HCC after SVR in chronic hepatitis C.

Hepatocellular Carcinoma after Achievement of Sustained Viral Response with Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND: Interferon-based antiviral therapies against hepatitis C virus (HCV) infection have been shown to reduce the incidence of hepatocellular carcinoma (HCC) in patients with sustained viral response (SVR). Recently, direct-acting antivirals (DAAs) have been proven to be much more effective in achieving SVR than interferon-based therapies. However, whether DAAs can efficiently prevent the occurrence of HCC after SVR remains controversial. To clarify this issue, we analyzed the clinical features of patients in whom HCC developed after achievement of SVR with DAAs for chronic HCV infection. SUMMARY: Among patients who achieved SVR with daclatasvir and asunaprevir (n = 100), HCC developed in 17 patients (HCC group; n = 17) and did not develop in 83 patients (non-HCC group; n = 83) during a mean observation period of 15 months. A multivariate Cox proportional hazards analysis identified past history of HCC and male sex as significant risk factors for the emergence of HCC after DAAs. Sixteen cases with HCC after DAAs were in the very early or early stage (16/17, 94.1%), and one case was in the advanced stage (1/17, 5.9%) with portal venous tumor thrombus. Radiofrequency ablation and/or transarterial chemoembolization were performed in most cases as curative therapy (16/17, 94.1%). Key Messages: SVR by DAAs did not completely prevent the occurrence of HCC. However, even if HCC did develop after SVR, curative anticancer therapy was applicable in most cases.

Unique Characteristics Associated with Sustained Liver Damage in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) dramatically improve the sustained virological response (SVR) of chronic hepatitis C (CHC) patients. However, continuous liver damage after SVR may be a risk of hepatocellular carcinoma (HCC). We clarified pretreatment characteristics related to sustained liver damage after SVR. METHODS: A total of 286 CHC patients were treated with an interferon-free DAA regimen. Among them, 250 patients achieved SVR for 12 weeks after the end of treatment (SVR12); these individuals were classified based on α-fetoprotein (AFP) and alanine transaminase (ALT) levels posttreatment. Baseline characteristics significantly associated with AFP >5 ng/mL and ALT level ≥20 IU/L after SVR were clarified using multivariate analyses. RESULTS: Among the pretreatment factors examined, serum AFP values and the presence of fatty liver (FL) were significantly associated with abnormal AFP (p < 0.0001) and ALT levels 12 weeks after SVR12 (SVR24; p = 0.0109). For 126 patients who showed an increase in baseline AFP level, FL, fibrosis-4 (FIB-4) index, and albumin levels before treatment were related to abnormal AFP at SVR24 (p = 0.0005, 0.0232, and 0.0400 for FL, FIB-4 index, and albumin, respectively). Similarly, for 150 patients with abnormal baseline ALT levels, FL was associated with an ALT level ≥ 30 IU/L after SVR (p = 0.0430). CONCLUSIONS: High FIB-4 index, low albumin level, and FL before DAA treatment were associated with a risk of sustained liver damage with AFP and ALT elevation after SVR; patients with these factors should be carefully monitored for emergence of HCC.

Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2.

BACKGROUND: Tumors classified based on the Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are heterogeneous in nature. Previously, the Kinki criterion was proposed for a more precise subclassification of tumors in BCLC-stage B. However, tumors in sub-stage B2 include various size and number of HCCs even with the Kinki criteria, which could lead to heterogeneity for overall survival (OS). In this study, we assessed how the size and number of tumors affect the OS and time to progression (TTP) in patients with Kinki criteria stage B2 tumors and treated with transarterial chemoembolization (TACE). METHODS: Of 906 HCC patients treated with TACE at Kindai University Hospital, 236 patients with HCC considered as Kinki criteria stage B2 were examined. They were classified into the following 4 groups according to the maximum tumor diameter and number of tumors: B2a group, tumor size ≤6 cm and total number of tumors ≤6; B2b group, size ≤6 cm and number >6; B2c group, size >6 cm and number ≤6; and B2d group, size >6 cm and number >6. The OS and TTP of patients in each group were compared. RESULTS: There were 131 patients (55.5%) in the B2a group, 58 (24.6%) in the B2b group, 41 (17.4%) in the B2c group, and 6 (0.03%) in the B2d group. Comparison of the survivals revealed that the median OS was 2.8 years (95% CI 2.0-3.5) in the B2a group, 2.8 years (95% CI 2.0-3.3) in the B2b group, 1.9 years (95% CI 0.8-4.0) in the B2c group, and 2.3 years (95% CI 1.2-ND [no data]) in the B2d group, respectively (p = 0.896). The median TTP in B2a, B2b, B2c, and B2d sub-substage HCC were13.2, 12.1, 13.8, and 11.5 months, respectively (p = 0.047). The median TTP in B2a + B2c sub-substage patients was longer than that in B2b + B2d sub-substage HCC patients (14.0 months and 10.4 months; p = 0.002). CONCLUSION: No significant differences were observed in the OS among HCC patients subclassified based on the maximum tumor diameter and tumor number in Kinki criteria stage B2. Consequently, Kinki criteria stage B2 HCC is a homogeneous subgroup in terms of OS prediction. However, shorter TTP in B2b+B2c sub-substage HCC patients than that in B2a + B2c sub-substage HCC patients suggests that different treatment strategy, such as systemic therapy with targeted agents instead of TACE, may be suitable to preserve the liver function.

Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2.

BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B. However, because of the heterogeneity of HCC in BCLC stage B; various subclassification systems have been proposed to predict the prognosis of patients. Previously, we proposed the Kinki criteria for precise classification of HCC cases in BCLC stage B. In this study, we compared the time to TACE refractoriness in HCC patients with Kinki criteria substages B1 and B2-HCC. SUMMARY: Between January 2006 and December 2013, 592 HCC patients (substage B1, n = 118; substage B2, n = 170) underwent TACE. Time to progression under TACE treatment was defined as the time to untreatable progression (TTUP). TTUP and changes in liver function were analyzed in patients with substages B1 and B2-HCC. The median TTUP was 25.7 months (95% CI 19.3-37.3) and 16.4 months (95% CI 13.1-20.2) in patients with substage B1-HCC and substage B2-HCC, respectively (p = 0.0050). In patients with substage B2-HCC, median Child-Pugh scores after the first TACE session was significantly different from those after third and fifth TACE sessions (first-third, p = 0.0020; first-fifth, p = 0.0008). Key Message: TACE refractoriness occurred earlier in patients with substage B2-HCC than those with substage B1-HCC; deterioration of liver function with repeated TACE was more obvious in HCC cases with stage-B1 tumor. Shorter TTUP and impaired liver function due to repeated TACE could be responsible for the shorter survival in patients with substage B2-HCC.