Percutaneous ethanol and lipiodol injection therapy for hepatocellular carcinoma

Radiofrequency ablation (RFA) therapy is of great significance in the treatment of hepatocellular carcinoma (HCC) or metastatic liver tumors. RFA is able to achieve widely coagulated necrosis in a few sessions without major complications. However, HCC cases exist that are resistant to RFA therapy for several reasons. In the present study, we performed injection of the mixture of ethanol and lipiodol (percutaneous ethanol-lipiodol injection therapy: PELIT) for HCCs that lacked clear visuality of the entire shape of the tumor by ultrasonography (US) or computed tomography (CT), or that were difficult to treat with RFA alone due to their locations in the liver or due to severe liver dysfunction of the patients. Local recurrence rates of HCC treated with PELIT were shown to be low in patients followed up for at least 4 months. In all patients treated with PELIT, lipiodol was accumulated in the entire region of the tumor after several trials of PELIT and the accumulation was kept for many months. The biopsy examination from the tumor treated with PELIT showed that HCC cells were totally destroyed by the PELIT. Although RFA therapy serves as a central role for the treatment of HCCs, PELIT, considered to be milder therapy, is likely to be important as a supportive treatment for HCCs and useful for the treatment of HCCs that are difficult to treat with RFA.     

A case of peritoneal metastasis of gastric cancer responding to TS-1, administered for four consecutive weeks with two-week rests

We treated a patient with gastric cancer considered to be unresectable due to peritoneal metastasis, who responded remarkably to treatment with TS-1. The patient was a 62-year-old male. His diagnosis was gastric cancer, for which he underwent surgery on February 22, 2001. Laparotomy disclosed many nodules measuring 2-3 mm in diameter in the abdominal cavity, so rapid pathological tests were conducted during the operation. The test results indicated peritoneal metastasis from gastric cancer. Therefore, simple laparotomy was employed as the best option. On day 13 after surgery, oral administration of TS-1, bid., at a daily dose of 120 mg was commenced. In our outpatient clinic, he was given 3 courses, each comprising 4 weeks' medication and 2 weeks' discontinuation. Subsequently, upper digestive tract endoscopy was performed but only scars in the gastric vestibular area were observed. Biopsy could not detect any malignant findings. Medication was discontinued due to the patient's preference and he died of gastric cancer 10 months after operation.     

Results of vitrectomy performed at the time of phacoemulsification complicated by intravitreal lens fragments

AIM: To evaluate outcome of vitrectomy performed at the time of phacoemulsification complicated by intravitreal lens material. METHODS: Clinical records associated with consecutive 8536 phacoemulsification procedures were reviewed retrospectively. RESULTS: 17 (0.20%) eyes had a posterior capsule rupture with retained lens material in the vitreous cavity that required vitrectomy. Final visual acuity was 0.5 or better in 14 eyes (82%) and 0.4 to 0.1 in three eyes (18%). Retinal detachment occurred in one eye during vitrectomy and two after the surgery. Cystoid macular oedema was observed in two eyes and none developed glaucoma. The corneal endothelial cell loss was 5.7% (SD 6.8 %) (n=15) at 3-6 months postoperatively. CONCLUSIONS: Combined vitrectomy and intraocular lens implantation at the time of phacoemulsification complicated by intravitreal lens material is an option to be considered to reduce the risk of postoperative complications including secondary glaucoma and corneal endothelial cell damage.     

Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Aim

The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC).

Methods

A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child–Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI.

Results

Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child–Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649–0.781; specificity/sensitivity = 0.644/0.688).

Conclusion

These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev.     

Diagnostic accuracy of enhanced liver fibrosis test for nonalcoholic steatohepatitis-related fibrosis: Multicenter study

Aim

The enhanced liver fibrosis (ELF) test is a noninvasive method for diagnosing hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). This multicenter cohort study aimed to evaluate the accuracy of the ELF test and compare it with other noninvasive tests in Japan.

Methods

We analyzed 371 Japanese patients with biopsy-proven NAFLD. We constructed area under the receiver operator characteristic curves (AUROC) to determine the diagnostic accuracies of the ELF test, the Mac-2-binding protein glycosylation isomer (M2BPGi), the Fibrosis-4 (FIB-4) index, and combinations of these indices.

Results

In patients with F0/F1/F2/F3/F4 fibrosis, the median values of the ELF test were 8.98/9.56/10.39/10.92/11.41, respectively. The AUROCs of the ELF test for patients with F0 versus F1–4, F0–1 versus F2–4, F0–2 versus F3–4, and F0–3 versus F4 fibrosis were 0.825/0.817/0.802/0.812, respectively. The AUROCs of the ELF test were greater than those of the FIB-4 index and M2BPGi at each fibrosis stage. Respective low and high cut-off values yielded sensitivities and specificities for predicting advanced fibrosis (≥F3) of 91.1% and 50.8%, and 38.5% and 92.8%, respectively. For F3 or F4 fibrosis, the combined values from the ELF test and FIB-4 index showed a sensitivity of 98.5%, and the combined values from the ELF test and M2BPGi assay showed a specificity of 97.5%.

Conclusions

In Japan, the ELF test predicts NAFLD-related fibrosis from its early stages. The diagnostic ability of the ELF test was not inferior to that of other indices, and the combined values of ELF plus other indices were more accurate.     

Association between microRNA-527 and glypican-3 in hepatocellular carcinoma

The present study aimed to identify the specific microRNAs (miRNAs/miRs) and their corresponding target genes involved in hepatocellular carcinomas (HCCs). Microarray analysis was performed to examine the miRNA expression profiles of four paired HCC and corresponding non-cancerous (N) liver tissues using 985 miRNA probes. The Human miRNA Target database was used to identify the target genes of differentially expressed miRNAs between the HCC and N tissues. The protein expression levels of target genes in the HCC tissues and cell lines were evaluated using western blotting. miRNA-mediated suppression of target gene expression was evaluated by transiently transfecting the miRNA into the HCC cell lines. Of the 985 miRNAs evaluated, four miRNAs were differentially expressed (three upregulated and one downregulated miRNAs). Of these four miRNAs, miRNA-527 was highly downregulated in the HCC tissues. Glypican-3 (GPC-3) was predicted as a target gene of miRNA-527. Western blotting revealed that GPC-3 protein is highly expressed in the HCC tissues and HCC cell lines compared with N and normal cell lines. Transfection with miR-527 resulted in suppression of GPC-3 protein expression in the Cos7 cells. Furthermore, transfection with miR-527 also inhibited the intrinsic expression of GPC-3 in the Huh-7 cell line. This indicated that miR-527 in the HCC tissues may be an important novel miRNA that targets the GPC-3 gene expression. GPC-3, whose expression is regulated by miR-527, may be involved in the development and progression of HCC.     

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages

Introduction

Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed.

Methods

We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells.

Results

Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1⁺ CD11c⁺ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3⁺ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1⁺ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1⁺ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17⁺ NK1.1⁺ NKT cells.

Conclusion

These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.     

Relation of aortic arch complex plaques to risk of cerebral infarction in patients with aortic stenosis

Aortic stenosis (AS) and systemic atherosclerosis have been shown to be closely related. We evaluated the prevalence of aortic arch plaques and their possible association with the risk of cerebral infarction in patients with severe AS. Transesophageal echocardiography was performed in 116 patients with severe AS (55 men, mean age 71 ± 7 years, mean aortic valve area 0.68 ± 0.15 cm(2)) who were scheduled for aortic valve replacement. The presence, thickness, and morphology of the aortic arch plaques were evaluated using transesophageal echocardiography. Cerebral infarcts (chronic cerebral infarction and cerebral infarction after cardiac catheterization and aortic valve replacement) were assessed in all patients. Compared to age- and gender-matched control subjects, the patients with severe AS had a significantly greater prevalence of aortic arch plaques (74% vs 41%; p <0.0001) and complex arch plaques such as large plaques (≥4 mm), ulcerated plaques, or mobile plaques (30% vs 10%; p = 0.004). Multivariate logistic analyses showed that the presence of complex arch plaques was independently associated with cerebral infarction in patients with AS after adjusting for traditional atherosclerotic risk factors and coronary artery disease (odds ratio 8.46, 95% confidence interval 2.38 to 30.12; p = 0.001). In conclusion, the results from the present study showed that there is a greater prevalence of aortic arch plaques in patients with AS and that the presence of complex plaques is independently associated with cerebral infarction in these patients. Therefore, the identification of complex arch plaques using transesophageal echocardiography is important for risk stratification of cerebrovascular events in patients with severe AS.     

Targeting receptor tyrosine kinases in gastric cancer

Molecularly targeted therapeutic agents are constantly being developed and have been shown to be effective in various clinical trials.One group of representative targeted oncogenic kinases,the receptor tyrosine kinases(RTKs),has been associated with gastric cancer development.Trastuzumab,an inhibitor of ERBB2,has been approved for the treatment of gastric cancer,although other receptor tyrosine kinases,such as epidermal growth factor receptor,vascular endothelial growth factor,platelet-derived growth factor receptor,c-Met,IGF-1R and fibroblast growth factor receptor 2,are also activated in gastric cancer.The promising results of the trastuzumab clinical trial for gastric cancer resulted in the approval of trastuzumab-based therapy as a first-line treatment for human epidermal growth factor receptor 2-positive patients.On the other hand,the trial examining bevacizumab in combination with conventional chemotherapy did not meet its primary goal of increasing the overall survival time of gastric cancer patients;however,a significantly higher response rate and a longer progression-free survival were observed in the bevacizumab arm of the trial.Other clinical trials,especially phaseⅢtrials that have tested drugs targeting RTKs,such as cetuximab,panitumumab,gefitinib,erlotinib,figitumumab,sorafenib,sunitinib and lapatinib,have shown that these drugs have modest effects against gastric cancer.This review summarizes the recent results from the clinical trials of molecularly targeted drugs and suggests that further improvements in the treatment of advanced gastric cancer can be achieved through the combination of conventional drugs with the new molecularly targeted therapies.     

A case of plasmablastic lymphoma of the liver without human immunodeficiency virus infection

Plasmablastic lymphoma(PBL)is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization.Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be observed at extra-oral sites in HIV-negative patients.Epstein-Barr virus(EBV)may be closely related the pathogenesis of PBL.PBL shows different clinicopathological characteristics between HIV-positive and-negative patients.Here,we report a case of PBL of the liver in a 79-yearold HIV-negative male.The patient died approximately1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass.Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs.The neoplastic cells were diffusely positive for CD30,EBV,Bob-1,and CD38.The autopsy findings suggested a diagnosis of PBL.To our knowledge,the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection.