Summary
Background Transcatheter arterial chemoembolization (TACE) has been limited in palliative treatment of unresectable hepatocellular carcinoma (HCC) with major portal vein (PV) invasion due to ...the possibility of liver failure following embolization. Transcatheter arterial chemoinfusion (TACI) has been an option in such cases.
Aim To compare clinical outcomes after TACE vs. TACI in HCC patients with major PV occlusion.
Methods We compared clinical outcomes after TACE vs. TACI in HCC patients with major PV occlusion. From 2005 to 2007, 110 HCC patients with major PV thrombosis were treated with TACE (n = 49) or TACI (n = 61).
Results The morbidity rate was similar for both TACE (6.1%) and TACI (6.5%) patients, and complications were adequately managed using medical treatment. The Kaplan–Meier survival analysis showed that the survival period was significantly longer for the TACE group (median: 14.9 months) than for the TACI (median: 4.4 months) group (P < 0.001). There was a higher probability of death in the TACI group than in the TACE group in both our multivariate Cox‐proportional hazards (OR 3.09, P < 0.001) and the propensity score‐matched (27 pairs) cohort analyses (OR 2.27, P = 0.024).
Conclusions Transcatheter arterial chemoembolization can be safely performed in HCC patients with main PV occlusion. Compared with TACI, TACE may result in longer survival of HCC patients with major PV occlusion.
Background: Many patients with extranodal natural killer/T-cell lymphoma (NTCL) fail to the front-line therapy and need an effective second-line chemotherapy.
Patients and methods: This was ...single-institutional, phase II study. The primary end point was response rate and secondary end points were toxicity, time to treatment failure (TTF), and overall survival (OS). Patients with relapsed or refractory NTCL were eligible. They received the chemotherapy consisting of ifosfamide, methotrexate, etoposide, and prednisolone and it was repeated every 3 weeks.
Results: Thirty-two patients were enrolled and 15 patients had achieved partial remission (PR) or complete remission (CR) after the front-line chemotherapy. The International Prognostic Index scores were 0–1 in thirteen, 2 in five, 3 in five, and 4–5 in nine patients. Twelve and two patients achieved CR and PR, respectively. Median OS and TTF of all patients were 8.2 and 3.7 months, respectively. Non-hematologic toxic effects were well tolerated, but grade 3/4 leukopenia occurred in 11.7% of all cycles. Four patients developed febrile neutropenia and one patient died due to pneumonia.
Conclusions: This chemotherapy regimen was moderately effective for relapsed/refractory extranodal NTCL, nasal type. Toxic effects were moderate, but caution should be exercised to prevent severe infection.
Salinomycin has been shown to control breast cancer stem cells, although the mechanisms underlying its anticancer effects are not clear. Deregulation of cell cycle regulators play critical roles in ...tumorigenesis, and they have been considered as anticancer targets. In this study, we investigated salinomycin effect on cell cycle progression using OVCAR-8 ovarian cancer cell line and multidrug-resistant NCI/ADR-RES and DXR cell lines that are derived from OVCAR-8. Parental OVCAR-8 cells are sensitive to several anticancer drugs, but NCI/ADR-RES and DXR cells are resistant to several anticancer drugs. However, salinomycin caused cell growth inhibition and apoptosis via cell cycle arrest at G1 in all three cell lines. Salinomycin inhibited signal transducer and activator of transcription 3 (Stat3) activity and thus decreased expression of Stat3-target genes, including cyclin D1, Skp2, and survivin. Salinomycin induced degradation of Skp2 and thus accumulated p27Kip1. Knockdown of Skp2 further increased salinomycin-induced G1 arrest, but knockdown of p27Kip1 attenuated salinomycin effect on G1 arrest. Cdh1, an E3 ligase for Skp2, was shifted to nuclear fractions upon salinomycin treatment. Cdh1 knockdown by siRNA reversed salinomycin-induced Skp2 downregulation and p27Kip1 upregulation, indicating that salinomycin activates the APC(Cdh1)-Skp2-p27Kip1 pathway. Concomitantly, si-Cdh1 inhibited salinomycin-induced G1 arrest. Taken together, our data indicate that salinomycin induces cell cycle arrest and apoptosis via downregulation or inactivation of cell cycle-associated oncogenes, such as Stat3, cyclin D1, and Skp2, regardless of multidrug resistance.
Background
Classifications of intraductal papillary mucinous neoplasm (IPMN) remain ambiguous, especially for the mixed type. Factors predicting malignancy remain unclear. The aim of this study was ...to evaluate the usefulness of factors predicting malignancy in the new international consensus guidelines for resection of branch duct‐type (BD)‐IPMN and to compare them with those in the previous version.
Methods
A prospectively collected database of patients with biopsy‐proven BD‐IPMN was analysed to compare factors between the first and second consensus guidelines, particularly as predictors of malignancy.
Results
Of 350 patients with BD‐IPMN, sensitivity (0·724) and balanced accuracy (0·751) of the second guidelines were superior to those (0·639 and 0·730) in the first version at the expense of slightly reduced specificity (0·779 versus 0·822 for the first version) by random forest models. Multiple logistic regression analysis showed that main pancreatic duct dilatation greater than 5 mm (hazard ratio (HR) 4·54, 95 per cent confidence interval 2·45 to 8·41; P < 0·001), mural nodules (HR 6·27, 3·27 to 12·01; P < 0·001) and carbohydrate antigen 19–9 level above 37 units/ml (HR 4·03, 1·83 to 8·90; P = 0·001) were independent predictors of BD‐IPMN malignancy.
Conclusion
The new consensus guidelines provide better sensitivity, performance of factors predicting malignancy, and balanced accuracy in the diagnosis of BD‐IPMN malignancy. Size alone was limited in predicting malignancy. Variability in clinical significance of the individual factors associated with a risk of malignancy indicates the need for a tailored approach in the management of patients with BD‐IPMN.
Cyst size alone is not useful
Summary
Background
It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular ...carcinoma (HCC).
Aim
To reveal the clinical relevance of compact lipiodolisation after TACE.
Methods
We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not.
Results
Of the 490 patients, 409 (83.5%) were in Child–Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5–10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1‐, 3‐ and 5‐year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child–Pugh class, alpha‐fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival.
Conclusions
Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.
Autism spectrum disorders (ASD) are neurodevelopmental disorders, and their incidence is increasing worldwide. Increased exposure to environmental metal lead (Pb) has been proposed as a risk factor ...associated with ASD. In the present study, BTBR T+ tf/J (BTBR) mice with ASD-like behavioral characteristics and control FVB mice were exposed gestationally and/or neonatally to Pb, and compared with highly social FVB mice to investigate neuroimmunological abnormalities. IgG1 and IgG2a levels in fetal brains from BTBR dams exposed to Pb (BTBR-Pb) were significantly higher than those of BTBR-controls (BTBR-C). However, this change did not occur in FVB mice exposed to Pb. The IgG1:IgG2a ratio was higher in both fetal and postnatal brains of BTBR mice compared to FVB animals regardless of Pb exposure. The IL-4:IFN-γ ratio was elevated in BTBR-Pb relative to BTBR-C mice, but this ratio was not markedly affected following Pb exposure in FVB animals. These findings suggest the potential for a Pb-driven predominant T
H
2-like reactivity profile in brain microenvironment present in BTBR mice. Brain-derived neurotrophic factor was decreased in fetal and postnatal BTBR-Pb brains relative to BTBR-C brains but not in FVB-Pb relative to FVB-C mice. Taken together, data demonstrate that Pb exposure might contribute to developmental brain abnormalities associated with ASD, particularly in individuals with genetic susceptibility to ASD.
Summary
Background
While studies report a lower incidence of skin cancer in white patients with vitiligo compared with controls, the skin cancer incidence in Asian patients with vitiligo is unknown.
...Objectives
To quantify the incidence of melanoma and nonmelanoma skin cancer (NMSC) in Korean patients with vitiligo and compare it with matched nonvitiligo controls.
Methods
A retrospective matched cohort study was performed with 131 245 incident vitiligo cases and 2 624 900 age‐ and sex‐matched (1 : 20) controls at index date, who were selected from the Korean National Health Insurance database between January 2005 and December 2017. Stratified Cox proportional hazards regression (stratified by sex, birth year and index year) was used to calculate the hazard ratio (HR) of skin cancer in patients with vitiligo.
Results
Patients with vitiligo were followed up for a mean duration of 6·34 years compared with a follow‐up period of 6·27 years for matched controls. Ultraviolet (UV) treatment‐adjusted HR for melanoma in patients with vitiligo was 3·32 95% confidence interval (CI) 2·29–4·81 and 1·29 (95% CI 1·06–1·56) for NMSC. The HRs for melanoma and NMSC in the vitiligo population without a history of UV treatment were 3·37 (95% CI 2·32–4·90) and 1·35 (95% CI 1·11–1·64), respectively.
Conclusions
In contrast to white patients with vitiligo, the risk of skin cancer was increased in the Korean vitiligo population. However, it is noteworthy that the skin cancer incidence in Korean patients with vitiligo was lower than that of their white counterparts. Owing to possible ethnic differences in the susceptibility to skin cancer, skin cancer surveillance in the vitiligo population may be adjusted for race.
What's already known about this topic?
Prior studies have reported a lower incidence of melanoma and nonmelanoma skin cancer (NMSC) in white patients with vitiligo compared with nonvitiligo controls.
The skin cancer incidence in Asian patients with vitiligo is unknown.
What does this study add?
In contrast to white patients, the risk of both melanoma and NMSC was increased in Korean patients with vitiligo compared with controls.
Owing to possible ethnic differences in susceptibility to skin cancer, skin cancer surveillance in the vitiligo population should be adjusted for race.
Linked Comment: Gran. Br J Dermatol 2020; 182:825–826.
Clostridioides difficile is a spore‐forming, Gram‐positive, anaerobic pathogen that caused gastrointestinal illness. During dysbiosis, overgrowth of C. difficile resulting in higher levels of toxin ...production. Since Lactobacillus has been commonly used to alleviate gastrointestinal discomfort, this study aimed to investigate the effects of Lactobacillus isolated from kimchi on the quorum‐sensing and virulence factors of C. difficile 027. Among the isolated Lactobacillus strains, the acid and bile tolerant L. fermentum Lim2 was only able to reduce C. difficile 027 growth by one log10 CFU per ml. In keeping with this finding, C. difficile 027 growth was unaffected by either untreated or heat‐inactivated cell extracts from L. fermentum Lim2. Both untreated and heat‐inactivated cell extracts did, however, significantly reduce the autoinducer‐2 (AI‐2) activity of C. difficile 027, with the most prominent suppression effect (654‐fold) being found from 100 mg ml−1 of heat‐inactivated cell extract. A gene expression analysis indicated that in the presence of 100 mg ml−1 heat‐inactivated cell extract, the quorum‐sensing (luxS) and the virulence factors (tcdA, tcdB and tcdE) were significantly suppressed, whereas the negative regulator gene (tcdC) was significantly up‐regulated. Taken together, the significant anti‐pathogenic effect from L. fermentum Lim2 could potentially be used to treat C. difficile‐infections.
Significance and Impact of the Study
Clostridioides difficile is a Gram‐positive pathogenic bacteria that caused gastrointestinal illness via toxic production. The emergence of highly virulence and foodborne C. difficile strains has further increased the incident and severity of C. difficile‐infections (CDIs). Numerous studies have reported the immunomodulatory activity of Lactobacillus, a member of healthy gut microbiota, to maintain gastrointestinal health. Here, we successfully isolated L. fermentum Lim2 from kimchi, and identified a promising anti‐pathogenic effect against C. difficile 027, from the heat‐inactivated L. fermentum cell extract via suppression on the C. difficile 027 quorum‐sensing system and toxin production, which could potentially be used to treat and prevent CDIs.
Significance and Impact of the Study: Clostridioides difficile is a Gram‐positive pathogenic bacteria that caused gastrointestinal illness via toxic production. The emergence of highly virulence and foodborne C. difficile strains has further increased the incident and severity of C. difficile‐infections (CDIs). Numerous studies have reported the immunomodulatory activity of Lactobacillus, a member of healthy gut microbiota, to maintain gastrointestinal health. Here, we successfully isolated L. fermentum Lim2 from kimchi, and identified a promising anti‐pathogenic effect against C. difficile 027, from the heat‐inactivated L. fermentum cell extract via suppression on the C. difficile 027 quorum‐sensing system and toxin production, which could potentially be used to treat and prevent CDIs.
By placing ionic groups at chain termini of polyurethane stable dispersions of high solid content (45%) have been made with high swelling resistance at low ionic content (2%) (T2-650-45).
High solid ...and high stability waterborne polyurethanes were molecularly designed and synthesized. The positions and concentrations of the anionic groups were varied, along with the molecular weights of the polyol. It was found that the dispersions containing ionic groups at the chain termini (called terminal ions) gave the smallest dispersion size, and the highest dispersion stability and viscosity, whereas the hard ions, containing ionic groups in the hard segments, resulted in the greatest swelling in water. However, the mechanical and dynamic mechanical properties of the dispersion cast films were similar. It was demonstrated that highly stable dispersions with a high solid content (45%) can be obtained at a low ionic content (2%) by simply incorporating the ionic groups at the flexible chain ends. The results were interpreted in terms of the high mobility and low free energy of the chain ends.
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