Search

Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC)., Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified., Results: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03)., Conclusion: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Purpose: We propose a large-factor super-resolution (SR) method for performing SR on registered medical image datasets. Conventional SR approaches use low-resolution (LR) and high-resolution (HR) image pairs to train a deep convolutional neural network (DCN). However, LR-HR images in medical imaging are commonly acquired from different imaging devices, and acquiring LR-HR image pairs needs registration. Registered LR-HR images have registration errors inevitably. Using LR-HR images with registration error for training an SR DCN causes collapsed SR results. To address these challenges, we introduce a novel SR approach designed specifically for registered LR-HR medical images., Methods: We propose style-subnets-assisted generative latent bank for large-factor super-resolution (SGSR) trained with registered medical image datasets. Pre-trained generative models named generative latent bank (GLB), which stores rich image priors, can be applied in SR to generate realistic and faithful images. We improve GLB by newly introducing style-subnets-assisted GLB (S-GLB). We also propose a novel inter-uncertainty loss to boost our method's performance. Introducing more spatial information by inputting adjacent slices further improved the results., Results: SGSR outperforms state-of-the-art (SOTA) supervised SR methods qualitatively and quantitatively on multiple datasets. SGSR achieved higher reconstruction accuracy than recently supervised baselines by increasing peak signal-to-noise ratio from 32.628 to 34.206 dB., Conclusion: SGSR performs large-factor SR while given a registered LR-HR medical image dataset with registration error for training. SGSR's results have both realistic textures and accurate anatomical structures due to favorable quantitative and qualitative results. Experiments on multiple datasets demonstrated SGSR's superiority over other SOTA methods. SR medical images generated by SGSR are expected to improve the accuracy of pre-surgery diagnosis and reduce patient burden., (© 2023. CARS.)

Aim: Pulse steroid therapy occasionally causes drug-induced autoimmune-like hepatitis (DI-ALH), but the long-term outcome of treated patients is not well known. In this study, we investigated the long-term outcomes of DI-ALH due to pulse steroid therapy., Methods: We retrospectively reviewed the medical records of 405 patients treated with pulse high-dose methylprednisolone in Kurashiki Central Hospital. The frequency and clinicopathological characteristics of acute liver injury that occurred within 3 months after the therapy were analyzed. The diagnosis of DI-ALH was made according to the revised international autoimmune hepatitis group criteria., Results: Among the 405 patients treated with methylprednisolone, 61 (15.1%) had acute liver injury after the pulse steroid therapy, and DI-ALH was diagnosed in five patients (1.2%). Absence of oral prednisolone tapering after the pulse steroid therapy was a significant risk factor for the subsequent development of DI-ALH (odds ratio 11.9; p = 0.017). One patient was treated with 3 days of intravenous methylprednisolone followed by oral prednisolone. Two patients were treated with glycyrrhizin followed by oral prednisolone due to ineffectiveness of glycyrrhizin. Remission was achieved with glycyrrhizin alone, and spontaneous remission without drug therapy occurred in one patient each. During the median follow-up period of 34 months, no relapse was evident in all the patients without maintenance therapy., Conclusions: Pulse steroid therapy can cause DI-ALH, especially when subsequent prednisolone is not tapered. Prednisolone is effective for DI-ALH due to pulse steroid therapy, and can be safely withdrawn once remission is achieved., (© 2023 Japan Society of Hepatology.)

Background and Aims: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice., Methods: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD., Results: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001)., Conclusions: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: Immunotherapy using immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Although several ICI options are available, the treatment regimen for NSCLC with large size tumors (large NSCLC) is controversial and the efficacy of anti-CTLA-4 antibody is unclear. This study thus investigated potential biomarkers for CTLA-4 blockade., Patients and Methods: The correlation between tumor diameter and treatment duration was examined in patients with advanced NSCLC treated with anti-PD-1 antibody monotherapy in our institution. In addition, the ratio of tumor-infiltrating CD8 + T cells and regulatory T (Treg) cells in small and large size NSCLC was also evaluated using immunohistochemical staining. Finally, the efficacy of treatment with anti-CTLA-4 antibody against large NSCLC was investigated., Results: A negative correlation was found between tumor diameter and treatment duration in patients treated with anti-PD-1 antibody monotherapy. Immuno-histochemical staining revealed that Treg cell infiltration was significantly higher in large NSCLC tumors than in small tumors. Among the patients with large NSCLC, the ICI regimen including anti-CTLA-4 antibody showed significant efficacies., Conclusion: Anti-PD-1 antibody monotherapy might be less effective against large NSCLC due to the infiltration of Treg cells. Therefore, it might be appropriate for large NSCLC to select a treatment including an anti-CTLA-4 antibody, which can target Treg cells., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Several vaccines have been developed for coronavirus disease 2019 (COVID-19) and are used worldwide. Here we report a case of severe acute hepatitis induced by COVID-19 vaccination. A 54-year-old woman received two doses of the Pfizer-BioNTech COVID-19 mRNA vaccine and an additional dose of the Moderna COVID-19 mRNA vaccine. Seven days after the third dose, she noticed fatigue, appetite loss and dark urine. Laboratory tests were consistent with severe liver injury and jaundice. Anti-smooth muscle antibody and HLA-DR4 were positive; thus, we suspected that she had autoimmune hepatitis (AIH). Intravenous methylprednisolone followed by oral prednisolone were administered. Because remission was not achieved, we performed percutaneous liver biopsy. Histologically, pan-lobular inflammation with moderate infiltration of lymphocytes and macrophages, interface hepatitis, and rosette formation were present. We regarded these findings as confirmation of the diagnosis of AIH. As she had not responded to corticosteroids, we added azathioprine. Liver biochemistry tests gradually improved, and prednisolone could be tapered without relapse of AIH. Dozens of cases of AIH after COVID-19 vaccination have been reported. Corticosteroids were effective in most cases, but some patients have died from liver failure after vaccination. This case illustrates the efficacy of azathioprine for steroid-refractory AIH induced by COVID-19 vaccination., (© 2023. Japanese Society of Gastroenterology.)

Background and Aims: Antibiotic prophylaxis is recommended for cirrhotic patients with upper gastrointestinal bleeding (UGIB). However, the frequency of bacterial infection in such patients has remarkably decreased over the decades, which has reduced the necessity for prophylaxis. Therefore, here we investigated the real-world adherence and effectiveness of antibiotic prophylaxis in cirrhotic patients with UGIB in Japan., Methods: This population-based study was conducted with a Japanese real-world database of the Health, Clinic, and Education Information Evaluation Institute. We enrolled cirrhotic patients who were hospitalized for UGIB between April 2010 and March 2020. After those who died within 24 h and who had aspiration pneumonia at admission were excluded, 1232 patients were analyzed. Rates of 6-week mortality, in-hospital bacterial infection, 30-day readmission, and length of hospital stay were evaluated., Results: Prophylactic antibiotics were prescribed in 142 (11.5%) patients. Multivariate analysis revealed that antibiotic prophylaxis was not significantly associated with either 6-week mortality or bacterial infection. After propensity score matching, the rates of 6-week mortality (7.2% vs. 8.4%, P = 0.810), bacterial infection (9.6% vs. 4.2%, P = 0.082), and 30-day unexpected readmission (7.2% vs. 7.8%, P = 1.000) were similar in patients with and without prophylaxis, whereas the median length of hospital stay was significantly longer in patients with prophylaxis (17 days vs. 13 days, P = 0.013)., Conclusions: Under current real-world circumstances in Japan, prophylactic antibiotics were prescribed in only 11.5% of cirrhotic patients with UGIB and were not associated with better clinical outcomes., (© 2023. Japanese Society of Gastroenterology.)

A 65-year-old woman with HER2-positive gastric cancer with multiple liver metastases underwent first conversion surgery of gastrectomy with D2 lymph nodes dissection and three liver metastases after combination therapy with capecitabine, cisplatin, and trastuzumab. Two years later, she experienced multiple liver metastases that were refractory to combination therapy with paclitaxel albumin-bound nanoparticles and ramucirumab. She participated in the DESTINY-Gastric01 trial and received tri-weekly trastuzumab deruxtecan as third-line treatment for 26 cycles. The recurrent lesions markedly shrank, and this effect continued for 19 months. We then performed partial hepatectomy for the one remaining lesion. No adjuvant chemotherapy was given, and she remains alive without recurrence 18 months after the second conversion surgery. Trastuzumab deruxtecan may generate a notable tumor response and subsequent conversion surgery could be a treatment option for HER2-positive stage IV gastric cancer., (© 2023. Japanese Society of Gastroenterology.)

Background: Endoscopic gastroduodenal stent (GDS) placement is widely used as a safe and effective method to rapidly improve gastrointestinal symptoms of malignant gastric outlet obstruction (MGOO). While previous studies reported the utility of chemotherapy after GDS placement for prognosis improvement, they did not fully address the issue of immortal time bias., Objectives: To examine the association between prognosis and clinical course following endoscopic GDS placement, using a time-dependent analysis., Design: Multicenter retrospective cohort study., Methods: This study included 216 MGOO patients who underwent GDS placement between April 2010 and August 2020. Data of patient baseline characteristics, including age, gender, cancer type, performance status (PS), GDS type and length, GDS placement location, gastric outlet obstruction scoring system (GOOSS) score, and history of chemotherapy before GDS were collected. The clinical course following GDS placement was evaluated by GOOSS score, stent dysfunction, cholangitis, and chemotherapy. A Cox proportional hazards model was used to identify prognostic factors after GDS placement. Stent dysfunction, post-stent cholangitis, and post-stent chemotherapy were analyzed as time-dependent covariates., Results: Mean GOOSS scores before and after GDS were 0.7 and 2.4, respectively, with significant improvement after GDS placement ( p  < 0.001). The median survival time after GDS placement was 79 [95% confidence interval (CI): 68-103] days. In multivariate Cox proportional hazards model with time-dependent covariates, PS 0-1 [hazard ratio (HR): 0.55, 95% CI: 0.40-0.75; p  < 0.001], ascites (HR: 1.45, 95% CI: 1.04-2.01; p  = 0.028), metastasis (HR: 1.84, 95% CI: 1.31-2.58; p  < 0.001), post-stent cholangitis (HR: 2.38, 95% CI: 1.37-4.15; p  = 0.002), and post-stent chemotherapy (HR: 0.01, 95% CI: 0.002-0.10; p  < 0.001) significantly affected prognosis after GDS placement., Conclusion: Post-stent cholangitis and tolerability to receive chemotherapy after GDS placement influenced prognosis in MGOO patients., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)

Background: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high-dose corticosteroids are usually effective in treatment of ICI-related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI-related liver injury that relapses under corticosteroid therapy after temporary remission., Case: Here we report two cases of ICI-related liver injury successfully treated with mycophenolate mofetil (MMF). In the first case, a 74-year-old man with stage IIIA lung cancer underwent curative chemoradiotherapy. After the second infusion of durvalumab, grade 3 ICI-related liver injury (mixed pattern) developed. In the second case, a 46-year-old man with stage IVB lung cancer received pembrolizumab-containing chemotherapy. After the first cycle, grade 2 ICI-related hepatitis developed. In the both cases, liver injury improved with high-dose prednisolone but relapsed during tapering of the drug. After liver biopsy was performed to confirm the diagnosis of ICI-related liver injury, MMF (2000 mg/day) was added. MMF was effective for both patients and permitted discontinuation or reduction of prednisolone., Conclusion: MMF appears to be an appropriate treatment option for ICI-related liver injury that respond to high-dose corticosteroids but relapse during steroid tapering., (© 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Combination therapy using multiple antiemetic drugs is recommended for intravenous administration of cisplatin, a highly emetogenic agent, whereas a 5-HT3 receptor antagonist alone is commonly used in hepatic arterial infusion chemotherapy using cisplatin for hepatocellular carcinoma owing to its less toxicity than that in the intravenous administration. Given that optimal antiemetic therapy is not yet established, we retrospectively investigated the efficacy of antiemetic drugs for hepatic arterial infusion chemotherapy using cisplatin. This study enrolled 72 patients with hepatocellular carcinoma who received hepatic arterial infusion chemotherapy using cisplatin at Kurashiki Central Hospital between January 2011 and May 2019. A 5-HT3 receptor antagonist was used in all cases, while aprepitant and/or dexamethasone were used concomitantly in 6 cases. After chemotherapy, a complete response rate for 5 days was achieved in 73.6% of the patients; however, complete control could be achieved only in 29.2%. During these 5 days, both rates were lower on days 2-5 than on day 1. In addition, younger age was associated with worse control rates. Our findings suggest that more effective antiemetic therapy is needed for hepatic arterial infusion chemotherapy using cisplatin, especially in non-elderly patients.

Purpose: We propose a super-resolution (SR) method, named SR-CycleGAN, for SR of clinical computed tomography (CT) images to the micro-focus x-ray CT CT ( μ CT ) level. Due to the resolution limitations of clinical CT (about 500 × 500 × 500    μ m 3 / voxel ), it is challenging to obtain enough pathological information. On the other hand, μ CT scanning allows the imaging of lung specimens with significantly higher resolution (about 50 × 50 × 50    μ m 3 / voxel or higher), which allows us to obtain and analyze detailed anatomical information. As a way to obtain detailed information such as cancer invasion and bronchioles from preoperative clinical CT images of lung cancer patients, the SR of clinical CT images to the μ CT level is desired. Approach: Typical SR methods require aligned pairs of low-resolution (LR) and high-resolution images for training, but it is infeasible to obtain precisely aligned paired clinical CT and μ CT images. To solve this problem, we propose an unpaired SR approach that can perform SR on clinical CT to the μ CT level. We modify a conventional image-to-image translation network named CycleGAN to an inter-modality translation network named SR-CycleGAN. The modifications consist of three parts: (1) an innovative loss function named multi-modality super-resolution loss, (2) optimized SR network structures for enlarging the input LR image to 2 k -times by width and height to obtain the SR output, and (3) sub-pixel shuffling layers for reducing computing time. Results: Experimental results demonstrated that our method successfully performed SR of lung clinical CT images. SSIM and PSNR scores of our method were 0.54 and 17.71, higher than the conventional CycleGAN's scores of 0.05 and 13.64, respectively. Conclusions: The proposed SR-CycleGAN is usable for the SR of a lung clinical CT into μ CT scale, while conventional CycleGAN output images with low qualitative and quantitative values. More lung micro-anatomy information could be observed to aid diagnosis, such as the shape of bronchioles walls., (© 2022 The Authors.)