Reevaluation of Makuuchi's criteria for resecting hepatocellular carcinoma: A Japanese nationwide survey.

AIM: Although Makuuchi's criteria are widely used to determine the cut-off for safe liver resection, there have been few reports of concrete data supporting their validity. Here, we verified the utility of Makuuchi's criteria by comparing the operative mortality rates associated with liver resection between hepatocellular carcinoma (HCC) patients meeting or exceeding the criteria. METHODS: A database was built using data from 15 597 patients treated between 2000 and 2007 for whom values for all three variables included in Makuuchi's criteria for liver resection (clinical ascites, serum bilirubin, and indocyanine green clearance) were available. The patients were divided into those fulfilling (n = 12 175) or exceeding (n = 3422) the criteria. The postoperative mortality (death for any reason within 30 days) and long-term survival were compared between the two groups. RESULTS: The operative mortality rate was significantly lower in patients meeting the criteria than in those exceeding the criteria (1.07% vs. 2.01%, respectively; p < 0.001). On multivariate analysis, exceeded the criteria was significantly associated with the risk for operative mortality (relative risk 2.08; 95% confidence interval (CI), 1.23-3.52; p = 0.007). Surgical indication meeting or exceeding the criteria was an independent factor for overall survival (hazard ratio 1.27; 95% CI, 1.18-1.36; p < 0.001). CONCLUSION: Makuuchi's criteria are suitable for determining the indication for resection of HCC due to the reduction in risk of operative mortality.

Utility of sonic hedgehog and keratin 8/18 immunohistochemistry for detecting ballooned hepatocytes.

AIMS: Ballooned hepatocytes represent liver cell degeneration and are histological hallmarks in the diagnosis of non-alcoholic steatohepatitis, a severe form of non-alcoholic fatty liver disease. However, the identification of ballooned hepatocytes is often difficult, especially in the clinical setting of patients with other chronic liver diseases. In this study, we investigated the utility of immunostaining for positive sonic hedgehog (SHh) protein and negative Keratin 8/18 (K8/18) expression on ballooned hepatocytes. METHODS AND RESULTS: Immunohistochemistry for SHh and K8/18 was evaluated independently by two experienced liver pathologists in non-tumorous liver tissue from 100 cases of resected hepatocellular carcinoma of various aetiology. The degree of hepatocyte ballooning was scored as follows: 0, none; 1, few; 2, many ballooned hepatocytes. These evaluations were performed using routine haematoxylin and eosin (H&E) staining, followed by immunostaining for SHh or K8/18. Using SHh or K8/18 immunostaining combined with H&E staining, the score of ballooned hepatocytes was upgraded in 20 and 19 cases, and downgraded in none and 2 cases, respectively. The percentage of observed agreement for ballooned hepatocytes scoring was 85% and 92%, and the weighted kappa value was 0.806 and 0.893 with SHh or K8/18 immunohistochemistry. Considering the immunohistochemistry results, background liver disease diagnosis was changed in 15 out of 100 cases (15%) evaluated. CONCLUSIONS: SHh and K8/18 immunohistochemistry are useful in detecting ballooned hepatocytes, regardless of background liver disease, and improving pathological diagnosis accuracy.

Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013).

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.

[Allogeneic hematopoietic stem cell transplantations for relapsed and refractory acute lymphoblastic leukemia following inotuzumab ozogamicin treatment].

Inotuzumab ozogamicin (InO) was administered in three cases of relapsed/refractory adult acute lymphoblastic leukemia (ALL) before allogeneic hematopoietic stem cell transplantation (allo-SCT). One case developed extremely severe sinusoidal obstruction syndrome (SOS) but recovered after receiving defibrotide therapy. A gap of 63 days in the SOS case was noted from the last administration of InO to allo-SCT, the duration was 133 and 86 days for the other two cases, and the remaining risk factors for SOS were comparable in the three cases. In contrast to gemtuzumab ozogamicin (GO), the interval between InO exposure and allo-SCT has not been reported as a risk for SOS. Nevertheless, this case suggests that the intervals should be as long as possible.

Effect of Diameter and Number of Hepatocellular Carcinomas on Survival After Resection, Transarterial Chemoembolization, and Ablation.

INTRODUCTION: Most studies predicting survival after resection, transarterial chemoembolization (TACE), and ablation analyzed diameter and number of hepatocellular carcinomas (HCCs) as dichotomous variables, resulting in an underestimation of risk variation. We aimed to develop and validate a new prognostic model for patients with HCC using largest diameter and number of HCCs as continuous variables. METHODS: The prognostic model was developed using data from patients undergoing resection, TACE, and ablation in 645 Japanese institutions. The model results were shown after balanced using the inverse probability of treatment-weighted analysis and were externally validated in an international multi-institution cohort. RESULTS: Of 77,268 patients, 43,904 patients, including 15,313 (34.9%) undergoing liver resection, 13,375 (30.5%) undergoing TACE, and 15,216 (34.7%) undergoing ablation, met the inclusion criteria. Our model (http://www.u-tokyo-hbp-transplant-surgery.jp/about/calculation.html) showed that the 5-year overall survival (OS) in patients with HCC undergoing these procedures decreased with progressive incremental increases in diameter and number of HCCs. For patients undergoing resection, the inverse probability of treatment-weighted-adjusted 5-year OS probabilities were 10%-20% higher compared with patients undergoing TACE for 1-6 HCC lesions <10 cm and were also 10%-20% higher compared with patients undergoing ablation when the HCC diameter was 2-3 cm. For patients undergoing resection and TACE, the model performed well in the external cohort. DISCUSSION: Our novel prognostic model performed well in predicting OS after resection and TACE for HCC and demonstrated that resection may have a survival benefit over TACE and ablation based on the diameter and number of HCCs.

Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).

In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.

Impact of hepatitis C virus on survival in patients undergoing resection of intrahepatic cholangiocarcinoma: Report of a Japanese nationwide survey.

AIM: We reviewed the data of a nationwide follow-up survey to determine the impact of hepatitis C virus (HCV) infection on the outcomes of hepatectomy for mass-forming (MF) type, and combined mass-forming and periductal infiltrating (MF + PI) type intrahepatic cholangiocarcinoma (ICC). METHODS: In total, 956 patients with ICC who underwent curative hepatic resection were included in this cohort study, and patients were classified according to virus status. Patients were classified according to virus status as follows: HCV-related ICC (n = 138, 14.4%), hepatitis B virus (HBV)-related ICC (n = 43, 4.5%) and non-virus-related ICC (n = 775, 81.1%). To control for variables, we used 1:1 propensity score-matching to compare outcomes after surgery between HCV-related (n = 102) and non-virus-related ICC cases (n = 102). RESULTS: We successfully matched HCV-related and non-virus-related ICC cases with similar liver function and tumor characteristics. Patients with HCV-related ICC had significantly shorter recurrence-free survival (hazard ratio 0.62, 95% confidence interval 0.42-0.92, p = 0.016) and overall survival (hazard ratio: 0.57, 95% confidence interval: 0.37-0.88, p = 0.011) than patients with non-virus-related ICC. Cox proportional hazard analysis showed that HCV-related ICC offered a worse prognosis than non-virus-related ICC. CONCLUSIONS: HCV infection increases the risk of recurrence and worsens overall survival in patients after curative resection for MF and combined MF + PI type ICC.

Analysis of Patient Outcome after Non-curative Resection for Hepatocellular Carcinoma Using Nationwide Survey Data in Japan.

BACKGROUND: Non-curative (debulking) hepatic resection for hepatocellular carcinoma (HCC) is occasionally applied for selected cases with bulky tumors or for oncologic emergency cases; however, the clinical usefulness of this procedure has not yet been fully evaluated. The aim of the present study was to evaluate the patient outcomes of non-curative hepatic resections for HCC using data from bi-annual nationwide surveys conducted in Japan. METHOD: Data of 1084 non-curative hepatic resections for HCC were collected. The patient outcomes were compared with those of curative resections, transcatheter arterial chemoembolization (TACE), and hepatic arterial infusion chemotherapy (HAIC). RESULTS: Patient survival after the non-curative resection was poorer than that after curative resection (P < 0.001) and was especially dismal in cases with extrahepatic tumor spread (lymph node metastasis, peritoneal seeding, or distant metastasis). As compared to cases receiving TACE without surgery, non-curative resections for multiple intrahepatic tumors were applied to cases with advanced tumors with good liver functional reserve. The survival outcomes were significantly more favorable in the TACE group, but the results became similar after propensity score matching of the patients. The survival outcome of patients receiving non-curative resections was better than that of cases treated by HAIC, with median survival times of 26.0 months and 10.0 months, respectively. CONCLUSION: The indications for non-curative hepatic resection in patients with HCC should be judged cautiously, especially in patients with extrahepatic tumor spread. This treatment approach may be beneficial for selected patients with intermediate- or advanced-stage HCC limited in liver and with good liver functional reserve.

[A Case of Rectosigmoid T1b Cancer Which Had Been Under Control by Combination of Loco-Regional Therapies].

According to the Japanese Colorectal ESD/EMR guidelines, radical surgery should be recommended for additional treatment of T1 colorectal cancer(CRC)if pathological findings of the lesion after endoscopic resection show unfavorable factors to be evaluated as curative resection, considering the probability of lymph node metastasis and general condition of patients. We report a case of a 74-year-old man with T1b rectosigmoid(RS)cancer, whose pulmonary metastasis(PM) was curatively resected during the postoperative period of ESD for primary lesions. The patient underwent ESD in November 2018 for Type 0-Isp CRC in the RS junction, revealed using colonoscopy, which was performed for the examination of blood stool in September 2018. The patient had suffered from pulmonary tuberculosis in his thirties and regularly visited our hospital for COPD. He was under close observation after ESD because the depth of the lesion, which was pathologically diagnosed as T1b, was the only factor evaluated as non-curative. In April 2020, chest CT and FDG-PET/CT findings revealed the occurrence of PM. Subsequently, video-assisted wedge resection of the lung was performed for the treatment of PM, which was pathologically confirmed with a size of 10 mm. The patient has survived relapse-free to date, for 30 months after the resection of the primary lesion.

Liver Resection for Multiple Hepatocellular Carcinomas: A Japanese Nationwide Survey.

OBJECTIVE: The aim of the study was to evaluate the survival benefits of liver resection (LR) compared with transarterial chemoembolization (TACE) for patients with multiple hepatocellular carcinomas (HCCs). BACKGROUND: Despite significant improvements in diagnostic imaging and the widespread application of screening programs, some patients with HCC continue to present with multiple tumors. The surgical indications for multiple HCCs remain controversial. METHODS: Among 77,268 patients with HCC reported in a Japanese nationwide survey, 27,164 patients had multiple HCCs. The exclusion criteria were Child-Pugh B/C, treatment other than LR and TACE, >3 tumors, and insufficient available data. Ultimately, 3246 patients (LR: n = 1944, TACE: n = 1302) were included. The survival benefit of LR for patients multiple HCCs was evaluated by using propensity score matching analysis. RESULTS: The study group of 2178 patients (LR: n = 1089, TACE: n = 1089) seemed to be well matched. The overall survival rate in the LR group was 60.0% at 5 years, which was higher than that in the TACE group (41.6%, P < 0.001). Among patients with a tumor size of 30 mm or more, LR showed a survival benefit over TACE at 5 years (53.0% vs 32.7%, P < 0.001). The multivariate analysis indicated that age, serum albumin level, serum alpha-fetoprotein (AFP) level, macrovascular invasion, tumor size, and TACE were independent predictors of poor prognosis in multiple HCCs. CONCLUSIONS: LR could offer better long-term survival than TACE for patients with multiple HCCs (up to 3 tumors). If patients have good liver function (Child-Pugh A), LR is recommended, even for those with multiple HCCs with tumor sizes of 30 mm or more.

Distinctive clinicopathological features and KRAS and IDH1/2 mutation status of cholangiolocellular carcinoma.

AIM: Cholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem-cell features (CHC-SC) in the latest World Health Organization classification. This subclassification of CHC-SCs is controversial and the relevance of such classification is unclear. METHODS: We analyzed a series of CHC-SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor. RESULTS: Background liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC-SC (CHCs-SC-int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha-fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19-9 (CA19-9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC-SC-int. In patients with iCCA, CLC, or CHC-SC-int, a histology of iCCA, microvascular invasion, and serum CA19-9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19-9 value was an independent poor prognostic factor for overall survival. CONCLUSIONS: Patients with CLC are likely to have a different etiology and mutational background from those with CHC-SC-int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.

Report of the 20th Nationwide follow-up survey of primary liver cancer in Japan.

In the 20th Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 075 new patients and 40 769 previously followed patients were compiled from 544 institutions over a 2-year period from 1 January 2008 to 31 December 2009. Compared with the previous 19th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, included more female patients, included more patients with non-B non-C HCC, had smaller tumor diameters and more frequently received radiofrequency ablation as local ablation therapy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and by background characteristics for patients newly registered between 1998 and 2009 whose final outcome was survival or death. Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment types (hepatectomy, local ablation therapy, and transcatheter arterial chemoembolization). Cumulative survival rates and median overall survival in patients treated by resection, transcatheter arterial chemoembolization, and local ablation therapy were calculated. The same values were also calculated by the registration date by dividing patients newly registered between 1978 and 2009 into four time period groups . The results of the analysis show that the prognosis of HCC is improving dramatically. It is expected that the data obtained from this nationwide follow-up survey will contribute to advancing clinical research, including the design of clinical trials, as well as the treatment strategy of primary liver cancer in the clinical practice setting.

Treatment Optimization for Hepatocellular Carcinoma in Elderly Patients in a Japanese Nationwide Cohort.

OBJECTIVE: We reviewed nationwide follow-up data to determine outcomes of different treatments for early-stage hepatocellular carcinoma (HCC) in elderly patients. SUMMARY BACKGROUND DATA: Outcomes of early-stage HCC treatments in elderly patients have not been prospectively compared. METHODS: We included 6490 HCC patients, aged ≥75 years at treatment, who underwent curative hepatic resection (HR, n = 2020), radiofrequency ablation (RFA, n = 1888), microwave ablation (MWA, n = 193), or transcatheter arterial chemoembolization (TACE, n = 2389), and compared their characteristics and survival. We used matching propensity score analysis (PSA) between the HR and RFA subgroups with tumors ≤3 cm to overcome baseline bias. RESULTS: The HR group had significantly longer recurrence-free survival (RFS) than the RFA, MWA, and TACE groups [RFA vs HR-hazard ratio: 1.22, 95% confidence interval (CI): 1.09-1.37, P < 0.001; MWA vs HR-hazard ratio: 1.51, 95% CI: 1.22-1.88, P < 0.001; TACE vs HR-hazard ratio: 2.70, 95% CI: 2.44-2.99, P < 0.001). HR and RFA patients had significantly longer overall survival (OS) than the TACE group (RFA vs HR-hazard ratio: 1.01, 95% CI: 0.87-1.17, P = 0.919, TACE vs HR-hazard ratio: 2.11, 95% CI: 1.86-2.40, P < 0.001). PSA successfully matched HR and RFA patients from with primary HCC tumors ≤3.0 cm and similar liver function and tumor characteristics; and showed significantly longer RFS (hazard ratio: 1.64, 95% CI: 1.29-2.10, P < 0.001) and OS (hazard ratio: 1.57, 95% CI: 1.12-2.20, P = 0.009) for HR than for RFA (including subgroup analyses). In Cox proportional hazard analysis, HR offered better prognosis than RFA. CONCLUSIONS: HR decreases recurrence risk and improves OS in patients aged ≥75 years with primary HCC tumors ≤3.0 cm.

Impact of Advanced Age on Survival in Patients Undergoing Resection of Hepatocellular Carcinoma: Report of a Japanese Nationwide Survey.

OBJECTIVE: The impact of age on survival after hepatic resection for hepatocellular carcinoma (HCC) has not been thoroughly examined. We reviewed the data of a nationwide follow-up survey to determine the outcomes of hepatectomy for HCC in elderly patients. BACKGROUND: Management of malignant diseases in elderly patients has become a global clinical issue because of the increased life expectancy worldwide. Advancements in surgical techniques and perioperative management have reduced age-related contraindications for liver surgery. METHODS: In all, 12,587 patients with HCC who underwent curative hepatic resection were included in this cohort study and classified according to age group [40-59 years (n = 2991), 60-74 years (n = 7576,), and ≥75 years (n = 2020)]. Clinicopathological features, long-term survival, and cumulative incidences of death after hepatic resection were compared among the groups. The cause-specific subdistribution hazard ratios for 3 types of death depending on age were also estimated. RESULTS: Preoperative liver function tests showed that the prothrombin activity and platelet count were higher in the ≥75-year age group than in the other age groups. The overall survival was significantly lower in the elderly than younger patients. However, recurrence-free survival was almost identical among the 3 groups. The cumulative incidence of HCC-related or liver-related death was almost identical among the 3 groups; however, the cumulative incidence of other causes of death was significantly different. The 60-year subdistribution hazard ratio for other causes of death increased remarkably with increasing age. CONCLUSIONS: Elderly patients in this nationwide survey had significantly worse overall survival after hepatectomy than middle-aged and young patients. The cumulative incidence of other causes of death in elderly patients was significantly different from that of HCC-related or liver-related death among the 3 groups.

Malic enzyme 1 is a potential marker of combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell type.

AIM: Combined hepatocellular cholangiocarcinoma, subtype with stem-cell features, intermediate-cell subtype (INT) shows various histological appearances and could be misdiagnosed as intrahepatic cholangiocarcinoma (iCCA). In the present study, we aimed to identify specific histological diagnostic markers of INT. METHODS: We extracted RNA from FFPE sections of six INT, five iCCA, and five hepatocellular carcinoma (HCC) cases and compared gene expression between INT, iCCA, and HCC by microarray analysis. We then undertook immunohistochemical (IHC) staining of potential key molecules identified by microarray analysis, the conventional hepatocytic marker, hepatocyte paraffin (HepPar)-1, and the cholangiocytic markers, keratin (K) 7 and K19, on 35 INT, 25 iCCA, and 60 HCC cases. RESULTS: Microarray analysis suggested that malic enzyme 1 (ME1) was significantly upregulated in INT. Immunohistochemical analysis revealed that the positive rates of ME1 in INT, iCCA, and HCC were 77.1% (27/35), 28.0% (7/25), and 61.7% (37/60), respectively. Analysis of classification and regression trees based on IHC scores indicated that HepPar-1 could be a good candidate for discriminating HCC from the others with high sensitivity (93.3%) and high specificity (96.7%). A multiple logistic regression model and receiver operating characteristic curve analysis based on the IHC scores of ME1, K7, and K19 generated a composite score that can discriminate between INT and iCCA. Using this composite score, INT could be discriminated from iCCA with high sensitivity (88.6%) and high specificity (88.0%). CONCLUSIONS: We propose that ME1 is a useful diagnostic marker of INT when used in combination with other hepatocytic and cholangiocytic markers.

Intrabiliary growth type of metastasis from colon cancer, 12 years after curative colectomy: a case report.

BACKGROUND: Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described. CASE PRESENTATION: An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9. He underwent right hemicolectomy for colon cancer 12 years prior. Enhanced computed tomography (CT) showed dilated bile ducts with periductal enhancement in S5; hence, cholangiocarcinoma was suspected. Upon anterior segmentectomy, we observed that the cut surface of the specimen exhibited a yellowish-white tumor within the bile ducts. Histologically, the tumor formed within the papillary process, extended along the lumen, and replaced the normal bile duct epithelium. Immunohistochemical studies showed that the liver tumor and primary colon cancer were negative for cytokeratin (CK) 7 and positive for CK20 and Caudal-type homeobox transcription factor 2 (CDX-2). In addition, both tumors showed a same KRAS mutation. We diagnosed the liver tumor as liver metastasis recurrence from colon cancer. CONCLUSION: Intrabiliary growth type of metastasis (IGM) is difficult to distinguish from cholangiocarcinoma, and sometimes develops long after surgery; thus, careful examination of a patient's history is needed in such cases.

[Relapse-Free Survival of over 54 Months after ESD Resection in an Elderly Patient Considered to Have Non-Curative Early Gastric Cancer].

According to the Japanese Gastric Cancer Treatment Guideline(GL), radical surgery is recommended as an additional treatment for early gastric cancer(EGC)patients with endoscopic submucosal dissection(ESD)evaluated as non-curative for fear of lymph node metastasis(LNM). However, the reported probability of LNM was approximately 10%. Therefore, the recommendation might be aggressive for elderly patients or those in poor physical conditions. Under this context, surveillance post non-curative ESD has emerged as an acceptable option. We reported a case of an elderly patient who survived EGC for over 54 months as relapse-free with ESD resection evaluated as non-curative. An 84-year-old woman underwent ESD in July 2014 for EGC, which was deemed as non-curative with negative surgical margins. The patient had pre-existing severe bronchial asthma. Given the age and the comorbidities, the patient preferred close surveillance to radical surgery. After 54 months of surveillance, no recurrence of the initial EGC was found. However, during the annual check-ups, 2 metachronous cancers were found in July 2016 and June 2018 respectively. Both metachronous cancers were curatively resected with ESD.

Liver resection for hepatocellular carcinoma associated with hepatic vein invasion: A Japanese nationwide survey.

Because of the rarity of hepatic vein tumor thrombus (HVTT) compared with portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma, little is known about this disease entity. The aim of this study was to evaluate the prognosis of each treatment modality for HVTT through an analysis of data collected in a Japanese nationwide survey. We analyzed data for 1,021 Child-Pugh A hepatocellular carcinoma patients with HVTT without inferior vena cava invasion registered between 2000 and 2007. Of these patients, 540 who underwent liver resection (LR) and 481 who received other treatments were compared. Propensity scores were calculated, and we successfully matched 223 patients (49.0% of the LR group). The median survival time in the LR group was 2.89 years longer than that in the non-LR group (4.47 versus 1.58 years, P < 0.001) and 1.61 years longer than that in the non-LR group (3.42 versus 1.81 years, P = 0.023) in a propensity score-matched cohort. After curative resection, median survival times were similar between patients with HVTT in the peripheral hepatic vein and those with HVTT in the major hepatic vein (4.85 versus 4.67 years, P = 0.974). In the LR group, the postoperative 90-day mortality rate was 3.4% (16 patients). In patients without PVTT, the median survival time was significantly better than that in patients with PVTT (5.67 versus 1.88 years, P < 0.001). CONCLUSION: LR is associated with a good prognosis in hepatocellular carcinoma patients with HVTT, especially in patients without PVTT. (Hepatology 2017;66:510-517).

Impact of resection and ablation for single hypovascular hepatocellular carcinoma ≤2 cm analysed with propensity score weighting.

BACKGROUND AND AIMS: Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated. METHODS: The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients. RESULTS: The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred. CONCLUSIONS: For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA.

Novel quantitative assessment system of liver steatosis using a newly developed attenuation measurement method.

AIM: The present study has developed and evaluated the effectiveness of a new echo attenuation measurement function combined with an ultrasonic diagnostic system for the accurate diagnosis of liver steatosis. METHODS: A multicenter prospective study involving patients with chronic hepatitis was carried out. All patients underwent liver biopsy, and attenuation coefficient (ATT) was measured on the same day. The fat area (%) of biopsy specimens was quantitatively evaluated. Correlations between ATT, steatosis grade, and fat area were evaluated. RESULTS: A total of 351 patients were enrolled in this study. The median values of fat area for steatosis grades S0, S1, S2, and S3 were 0.6%, 3.2%, 6.4%, and 15.5%, respectively. A significant correlation was found between fat area and steatosis grade (P < 0.001). Similarly, the median values of ATT for steatosis grades S0, S1, S2, and S3 were 0.55, 0.63, 0.69, and 0.85 dB/cm/MHz, respectively, and ATT increased with an increase in the steatosis grade (P < 0.001). Attenuation coefficient was significantly correlated with fat area (r = 0.50, P < 0.001). The area under the receiver operating characteristic curve corresponding to S ≥ 1, S ≥ 2, and S ≥ 3 were 0.79, 0.87, and 0.96, respectively. Similarly, the sensitivity and specificity of S ≥ 1, S ≥ 2, and S ≥ 3 were 72%, 82%, and 87% and 72%, 82%, and 89%, respectively. CONCLUSIONS: The newly developed ATT measurement for evaluation of liver steatosis was closely correlated with steatosis grade and automated quantification of fat area, and it provides clinically relevant information.