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BackgroundTranscatheter arterial chemoembolization (TACE) is widely used for unresectable hepatocellular carcinoma (HCC). The purpose of this study was to investigate incidence and risk factors of contrast-induced nephropathy (CIN) after TACE in patients with HCC.MethodsIn this single-center retrospective study, we examined 461 consecutive TACE sessions in 260 patients between January 2003 and October 2015. CIN was defined as an increase in serum creatinine levels by ≥ 0.5 mg/dl or ≥ 25% from baseline within 72 h after TACE. We calculated incidence rate of CIN and tried to identify its risk factors by logistic regression analysis.ResultsTwenty-one cases of CIN (5%) were observed in 461 TACE sessions. One patient required subsequent hemodialysis transiently. In univariate analysis, tumor size > 5 cm [odds ratio (OR) 5.76, 95% confidence interval (CI) 2.34–14.14, p < 0.001], chronic kidney disease (OR 2.54, 95% CI 1.05–6.14, p = 0.04), serum hemoglobin level [OR 0.79 (per 1 g/dl increase), 95% CI 0.64–0.98, p = 0.03] and serum albumin level [OR 0.44 (per 1 g/dl increase), 95% CI 0.19–1.02, p = 0.05] were associated with the development of CIN. Stepwise logistic regression methods showed that tumor size > 5 cm (OR 7.81, 95% CI 2.99–20.46, p < 0.001) and serum albumin [OR 0.29 (per 1 g/dl increase), 95% CI 0.11–0.75, p = 0.01] were risk factors of CIN.ConclusionsIn this study, HCC tumor size and lower serum albumin level were independent predictors of CIN after TACE.

This study aimed to evaluate Japanese patient preferences regarding features of intermediate or advanced (Progressed) hepatocellular carcinoma (HCC) treatments: transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and oral anti-cancer therapy. Patients with HCC, recruited from clinical sites and a patient panel in Japan, completed a cross-sectional web-based survey. Preferences were quantified using best-worst scaling, where patients identified the best and worst among 13 treatment features. Direct elicitation was used to identify preference for TACE, HAIC, or oral therapy, including the likelihood of trying each. Additional items asked for the willingness to try an oral medication that delays progression by six months but has an 8% or 21% risk of severe hand-foot skin reaction (HFSR). The sample (N=119; 29 early stage; 90 Progressed) most preferred \"oral medication\", \"artery branches plugged\", and \"prevents formation of new blood vessels\", and least preferred \"risk of liver damage\" and \"risk of catheter-related complications\". Overall, 51%, 40%, and 8% preferred oral therapy, TACE, and HAIC, respectively ( <0.05), and the mean likelihood of trying each were 59%, 52%, and 35%, respectively ( <0.001). Patients with sorafenib or TACE experience most preferred what they had received; however, both groups were equally willing to try the other treatment. Patients preferring oral therapy favored \"oral medication\" over \"artery branches plugged\", \"surgery is repeated as required when the cancer grows again\", and \"risk of liver damage\", compared to those preferring TACE ( <0.05). Sixty-eight percent would probably try therapy with an 8% risk of severe HFSR, compared to 50% with a 21% risk. Treatment type, mode of action, and risks may drive HCC patient preferences. Such features likely should be incorporated into physician-patient interactions regarding treatment decision-making.

Background: Prior to the approval of sorafenib, hepatic arterial infusion chemotherapy (HAIC) was offered to patients with advanced hepatocellular carcinoma (HCC) in East Asia, particularly Japan. According to the Japanese guidelines, HAIC is recommended as one of the treatment options in patients without extrahepatic metastasis (EHM). Methods: The present cohort study compared the use of HAIC and sorafenib on outcomes of patients with advanced HCC. Consecutive patients with advanced HCC who received HAIC or sorafenib as a first-line systemic therapy were enrolled from 10 Japanese institutions. The primary outcomes were overall survival (OS) in patients with macrovascular invasion (MVI), but without EHM, and OS in patients without both MVI and EHM. Results: Between 2009 and 2016, 2,006 patients were enrolled (541 HAIC patients, 1,465 sorafenib patients). After propensity score matching, the OS of patients with MVI but without EHM was significantly longer in the HAIC group compared with the sorafenib group (10.1 vs. 9.1 months for the HAIC and sorafenib groups, respectively; n = 170 for each group; hazard ratio [HR] 0.668; 95% confidence interval [95% CI] 0.475–0.935; p = 0.018). There was no significant difference in OS between patients without both MVI and EHM (12.2 vs. 15.4 months for the HAIC and sorafenib groups, respectively; n = 76 in each cohort after propensity score matching; HR 1.227; 95% CI 0.699–2.155; p = 0.475). Conclusion: HAIC is a potential front-line treatment choice in a subpopulation of patients with advanced HCC with MVI but without EHM.

Background Platelet (PLT) transfusion was the most practical way to increase patients’ PLT counts before invasive hepatic procedures such as radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). A novel drug that raises the PLT count by acting on the thrombopoietin receptor has recently become available. Methods Lusutrombopag 3 mg was administered daily for 7 days to patients who underwent RFA for liver tumors with low PLT counts (< 50,000 PLT µL − 1 ). We collected demographic data concerning the patients’ liver function and PLT counts. Results Lusutrombopag was administered to 91 patients, with a median age of 71 years (range 51–86). Forty-two patients had hepatitis C, 12 had hepatitis B, 21 had alcoholic liver disease, 11 had nonalcoholic steatohepatitis, and five had other diseases. The median Child-Pugh score was 7 (range 5–11). Thirty-seven patients had stage I tumors, 41 had Stage II, 12 had stage III, and one had stage IV. PLT count was elevated from 4.4 × 10 4  ± 1.4 × 10 4 to 8.6 × 10 4  ± 2.5 × 10 4 PLT µL − 1 . Lusutrombopag administration prevented PLT transfusions in 84/91 patients (92%). No patient had bleeding complications after RFA. One had portal thrombosis after lusutrombopag administration. Patients who achieved PLT counts of > 50,000 PLT µL − 1 had higher PLT counts before lusutrombopag administration. The degree of splenomegaly did not affect the rate of PLT count elevation. There was no specific adverse effect by administrating lusutrombopag for patients with PLT counts of around 50,000 µL − 1 but > 50,000 µL − 1 . Conclusions Lusutrombopag administration before RFA was effective and seemed to be relatively safe for hepatocellular carcinoma patients with low PLT counts. Trial registration This study was approved by Japanese Red Cross Medical Center Institutional Reseach Comittie (#862, 07/03/2016), and was registered in a publically accessible primary register (#UMIN000046629, registered date: 14/01/2022).

Background. Liraglutide leading to improve not only glycaemic control but also liver inflammation in non-alcoholic fatty liver disease (NAFLD) patients. Aims. The aim of this study is to elucidate the effectiveness of liraglutide in NAFLD patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and pioglitazone. Methods. We retrospectively enrolled 82 Japanese NAFLD patients with T2DM and divided into three groups (liraglutide: N = 26, sitagliptin; N = 36, pioglitazone; N = 20). We compared the baseline characteristics, changes of laboratory data and body weight. Results. At the end of follow-up, ALT, fast blood glucose, and HbA1c level significantly improved among the three groups. AST to platelet ratio significantly decreased in liraglutide group and pioglitazone group. The body weight significantly decreased in liraglutide group (81.8 kg to 78.0 kg, P<0.01). On the other hands, the body weight significantly increased in pioglitazone group and did not change in sitagliptin group. Multivariate regression analysis indicated that administration of liraglutide as an independent factor of body weight reduction for more than 5% (OR 9.04; 95% CI 1.12–73.1, P=0.04). Conclusions. Administration of liraglutide improved T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight.

Background and Objective Experience of the use of lenvatinib (LEN) in the clinical setting remains limited. We conducted this study to elucidate the factors associated with progression-free survival (PFS) in patients with advanced HCC treated with LEN. Methods In this multicenter retrospective study, we analyzed data on patient characteristics, treatment outcomes, and adverse events (AEs) for 77 patients with advanced hepatocellular carcinoma (HCC). We also analyzed PFS and factors that influence PFS. Results The response rate to LEN was 29.9% and the disease control rate was 77.9%. Patients who achieved relative dose intensities of more than 70% had better outcomes (response rate 45.2% vs. 11.4%, P  < 0.01). Appetite loss, fatigue, diarrhea, hypertension, and thyroid dysfunction were the most frequent AEs. Twenty-three patients (29.9%) had grade 3 or 4 AEs. Fifty-two patients (67.5%) required a dose reduction and 47 (61.0%) stopped taking the drug due to AEs. The PFS rates at 3, 6, and 12 months were 81.2%, 49.8%, and 34.8%, respectively. The median PFS was 5.6 months. Multivariate analysis showed that thyroid dysfunction of grade ≥ 2 (hazard ratio [HR] 4.57, 95% confidence interval [CI] 2.05–10.2, P  < 0.01), appetite loss (HR 3.58, 95% CI 1.72–7.52, P  < 0.01), and tumor diameter ≥ 40 mm (HR: 2.27, 95% CI 1.17–4.40, P  = 0.015) were independent factors associated with poor PFS. On the other hand, Child–Pugh class 5A (HR 0.41, 95% CI 0.19–0.90, P  = 0.027) and complete or partial response (HR 0.40, 95% CI 0.17–0.95, P  = 0.039) were independent factors associated with better PFS. Conclusions Thyroid dysfunction and appetite loss after the administration of LEN were independent factors associated with shorter PFS, so these AEs should be carefully managed after administering LEN.

Background While dermatomyositis is often associated with malignancy, several autoimmune diseases like myositis can be caused by immune checkpoint inhibitors. Differentially diagnosing malignancy-associated dermatomyositis or myositis caused by immune checkpoint inhibitors is sometimes difficult, particularly when a patient with malignancy shows the symptoms of myositis after checkpoint inhibitor administration. We experienced such a case in which we had difficulties in diagnosing paraneoplastic dermatomyositis or drug-associated myositis. In this case, all of our team initially assumed that the diagnosis was myositis caused by immune checkpoint inhibitors. However, it turned out finally that the diagnosis was paraneoplastic dermatomyositis. Because the diagnosis was unexpected, we report here. Case presentation We report the case of a 71-year-old Japanese man who developed clinical symptoms of myositis, such as muscle aches and weakness, after initiation of nivolumab therapy for his gastric cancer. He was initially diagnosed with nivolumab-induced myositis, because the myositis symptoms appeared after nivolumab administration, and nivolumab is known to trigger various drug-associated autoimmune diseases. However, according to his characteristic skin lesions, the type of muscle weakness, his serum marker profiles, electromyography of his deltoid muscle, and magnetic resonance imaging, he was finally diagnosed as having paraneoplastic dermatomyositis. Accordingly, treatment with intravenously administered corticosteroid pulse treatment, immunoglobulin injection, and tacrolimus was applied; his symptoms subsequently improved. However, to our regret, at day 142 after administration, he died due to rapid worsening of his gastric cancer. Conclusion Differentially diagnosing paraneoplastic dermatomyositis or drug-associated myositis caused by immune checkpoint inhibitors is difficult in some cases. The differential diagnosis is crucial because it influences the decision regarding the appropriateness of the use of immunosuppressive treatment against the autoimmune diseases as well as the decision regarding the appropriateness of the continuous use of immune checkpoint inhibitors against the primary cancers. Because subclinical autoimmune disease may become overt after administering immune checkpoint inhibitors, non-apparent autoimmune diseases, which have already existed, should also be considered to avoid the delay of appropriate treatment, when symptoms of autoimmune diseases are recognized.

Background Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is ordinarily indicated for those with three or fewer nodules, none of which exceeds 3 cm in diameter. This study investigated whether an apparent threshold exists in the diameter and number of nodules in terms of the prognosis of patients with HCC. Methods We enrolled 663 naïve patients with HCC who were treated with RFA at our hospital between 1999 and 2005. We analyzed the patients' prognosis using multivariate Cox proportional regression with the diameter and number of nodules as covariates and Child-Pugh class as a stratification factor. The diameter and number were categorized as <=2.0, 2.1-3.0, 3.1-4.0, 4.1-5.0, and >5 cm and 1, 2-3, 4-5, and >5, respectively. Results The adjusted hazard ratio of patients whose largest nodule was <=2.0, 2.1-3.0, 3.1-4.0, 4.1-5.0, and >5 cm was 1, 1.51, 2.56, 2.25, and 2.71, respectively. The adjusted hazard ratio of patients with one, two or three, four or five, and more than five nodules was 1, 1.35, 1.70, and 2.12, respectively. Therefore, patients with three or fewer nodules, none of which exceeds 5 cm in diameter, have a 5-year survival of 40%. Conclusions The prognosis of the patients worsened gradually as the diameter and number of nodules increased. No apparent threshold in the diameter or number of HCC nodules was detected. RFA can be applied beyond the conventional indications.

Background Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. Methods In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. Results Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44–8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08–16.2), and heart disease (OR 3.05; 95% CI 1.11–8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36–28.7). Conclusion In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

Background Although all types of endoscopic procedures harbor risk of aspiration, little is understood about risk factors for aspiration pneumonia developing after endoscopic hemostasis. Aims The present study aimed to identify risk factors for aspiration pneumonia after endoscopic hemostasis. Methods Charts from consecutive patients with upper gastrointestinal bleeding that had been treated by endoscopic hemostasis at a single center between January 2004 and January 2015 were retrospectively reviewed. Patient information and clinical characteristics including cause of hemorrhage, established prognostic scales, laboratory data, comorbidities, medications, duration of endoscopic hemostasis, vital signs, sedative use, and the main operator during the procedure were compared between patients who developed aspiration pneumonia and those who did not. Results Aspiration pneumonia developed in 24 (4.8 %) of 504 patients after endoscopic hemostasis. Endotracheal intubation was required for three of them, and one died of the complication. Multivariate analysis revealed that age >75 years (odds ratio (OR) 4.4; 95 % confidence interval (CI) 1.5–13.6; p  = 0.0073), procedural duration >30 min (OR 5.6; 95 % CI 1.9–18.2; p  = 0.0023), hemodialysis (OR 3.6; 95 % CI 1.2–11; p  = 0.024), and a history of stroke (OR 3.8; 95 % CI 1–14; p  = 0.041) were independent risk factors for developing aspiration pneumonia. Conclusions Specific risk factors for aspiration pneumonia after endoscopic hemostasis were identified. Endoscopists should carefully consider aspiration pneumonia when managing older patients who are on hemodialysis, have a history of stroke, and undergo a longer procedure.