Background
Laparoscopic liver resection (LLR) of high difficulty score is technically challenging. There is a lack of clinical evidence to support its applicability in terms of the long-term survival ...benefits. This study aims to compare clinical outcomes between LLR and the open liver resection of high difficulty score for hepatocellular carcinoma (HCC).
Materials and Methods
From 2010 to 2020, using Iwate criteria, 424 patients underwent liver resection of high difficulty score by the laparoscopic (
n
= 65) or open (
n
= 359) approach. Propensity score (PS) matching was performed between the two groups. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival.
Results
The laparoscopic group had significantly fewer severe complications (3% vs. 10.8%), and shorter median hospital stays (6 days vs. 8 days) than the open group. Meanwhile, the long-term oncological outcomes were comparable between the two groups, in terms of the tumor recurrence rate (40% vs. 46.1%), the 5-year overall survival rate (75.4% vs. 76.2%), and the 5-year recurrence-free survival rate (50.3% vs. 53.5%). The high preoperative serum alpha-fetoprotein level, multiple tumors, and severe postoperative complications were the independent poor prognostic factors associated with worse overall survival. The surgical approach (Laparoscopic vs. Open) did not influence the survival.
Conclusion
LLR of high difficulty score for selected patients with HCC has better short-term outcomes than the open approach. More importantly, it can achieve similar long-term survival outcomes as the open approach.
Mycelia of
Poria cocos were obtained from a pilot-scale 50-L fermenter by submerged cultivation biotechnology. Six polysaccharide fractions were extracted sequentially from the
P. cocos mycelia with ...0.9% NaCl (Pi-PCM1), hot water (Pi-PCM2), 0.5
M NaOH (Pi-PCM3-I and -II), and 88% formic acid (Pi-PCM4-I and -II). The supernatant of the culture media was spray-dried to obtain the extracellular polysaccharide (Pi-PCM0) produced by the mycelia. The results from Fourier transform infrared spectroscopy, gas chromatography, and
13C NMR revealed that the water-soluble fractions including Pi-PCM0, Pi-PCM1, and Pi-PCM2 were heteropolysaccharides mainly containing glucose, galactose, and mannose, whereas Pi-PCM3-I and Pi-PCM4-I had (1
→
3)-α-
d-glucan characteristics. The weight-average molecular mass (
M
w) and intrinsic viscosity (
η) of the polysaccharide were measured by laser light scattering (LLS) and viscometry, respectively. Results indicated that Pi-PCM1 and Pi-PCM2 existed as a compact random coil in aqueous solution, close to the global shape. Interestingly, the three water-soluble polysaccharides (Pi-PCM0 to Pi-PCM2) all exhibited antitumor activities
in vivo (Sarcoma 180 solid tumor implanted in BALB/c mice), and
in vitro (HL-60 tumor cell).
Microwave (MWA) and radiofrequency ablation are the commonly used local ablation for hepatocellular carcinoma (HCC). Studies comparing both techniques are scarce. The aim of this study was to compare ...the efficacy of MWA versus RFA as a treatment for HCC.
Patients with HCC who were suitable for local ablation were randomized into MWA or RFA. All patients were followed up regularly with contrast-enhanced computed tomography (CT) performed at 1, 3, 6 and 12 months after ablation. Both patients and the radiologists who interpreted the post-procedure CT scans were blinded to the treatment allocation. Treatment-related morbidity, overall and disease-free survivals were analyzed.
A total of 93 patients were recruited. Among them, 47 and 46 patients were randomized to MWA and RFA respectively. Patients in two groups were comparable in baseline demographics and tumor characteristics. With a median follow-up of around 30 months, there were no significant difference in the treatment-related morbidity, overall and disease-free survivals. MWA had a significantly shorter overall ablation time when compared with RFA (12 min vs 24 min, p < 0.001).
MWA is no different to RFA with respect to completeness of ablation and survivals. It is, however, as safe and effective as RFA in treating small HCC.
Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering ...the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.
We describe an introduction of clade GH severe acute respiratory syndrome coronavirus 2 causing a fourth wave of coronavirus disease in Hong Kong. The virus has an ORF3a-Q57H mutation, causing ...truncation of ORF3b. This virus evades induction of cytokine, chemokine, and interferon-stimulated gene expression in primary human respiratory cells.
Low-grade fibromyxoid sarcoma (LGFMS) is an uncommon sarcoma with a deceptively bland-looking morphology that disguises its malignant clinical behavior. It shows distinctive chromosomal ...translocations resulting in fusion of FUS with the CREB3L2 gene in most cases and CREB3L1 in rare cases. Thus molecular studies are particularly helpful in the diagnosis of this bland-looking sarcoma. We report 2 cases of LGFMS serendipitously found to harbor a novel alternative EWSR1-CREB3L1 gene fusion, as confirmed by DNA sequencing of reverse transcriptase-polymerase chain reaction products and fluorescence in situ hybridization. One patient was a child who presented with a subcutaneous nodule on the lower leg, and the other was a middle-aged woman who had a mass lesion over the proximal thigh. Morphologically, one case showed a spindle cell tumor with hyalinization and giant rosettes, whereas the other showed classical histology of LGFMS with focal metaplastic bone formation. Immunostaining for MUC4 showed extensive positive staining. Our findings therefore expand the spectrum of gene fusions that characterize LGFMS and suggest that the EWSR1 gene may substitute for the function of FUS in gene fusions of sarcoma.
Systematic testing of existing drugs and their combinations is an attractive strategy to exploit approved drugs for repurposing and identifying the best actionable treatment options. To expedite the ...search among many possible drug combinations, we designed a combinatorial CRISPR-Cas9 screen to inhibit druggable targets. Coblockade of the N-methyl-d-aspartate receptor (NMDAR) with targets of first-line kinase inhibitors reduced hepatocellular carcinoma (HCC) cell growth. Clinically, HCC patients with low NMDAR1 expression showed better survival. The clinically approved NMDAR antagonist ifenprodil synergized with sorafenib to induce the unfolded protein response, trigger cell-cycle arrest, downregulate genes associated with WNT signaling and stemness, and reduce self-renewal ability of HCC cells. In multiple HCC patient-derived organoids and human tumor xenograft models, the drug combination, but neither single drug alone, markedly reduced tumor-initiating cancer cell frequency. Because ifenprodil has an established safety history for its use as a vasodilator in humans, our findings support the repurposing of this drug as an adjunct for HCC treatment to improve clinical outcome and reduce tumor recurrence. These results also validate an approach for readily discovering actionable combinations for cancer therapy. SIGNIFICANCE: Combinatorial CRISPR-Cas9 screening identifies actionable targets for HCC therapy, uncovering the potential of combining the clinically approved drugs ifenprodil and sorafenib as a new effective treatment regimen.
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has emerged as a coronavirus infection of humans in the past 5 years. Though confined to certain geographical regions of the world, infection ...has been associated with a case fatality rate of 35%, and this mortality may be higher in ventilated patients. As there are few readily available animal models that accurately mimic human disease, it has been a challenge to ethically determine what optimum treatment strategies can be used for this disease. We used in-vitro and human ex-vivo explant cultures to investigate the effect of two immunomodulatory agents, interferon alpha and cyclosporine, singly and in combination, on MERS-CoV replication. In both culture systems the combined treatment was more effective than either agent used alone in reducing MERS-CoV replication. PCR SuperArray analysis showed that the reduction of virus replication was associated with a greater induction of interferon stimulated genes. As these therapeutic agents are already licensed for clinical use, it may be relevant to investigate their use for therapy of human MERS-CoV infection.
•The effect of interferon-α and/or cyclosporine on MERS-CoV replication was evaluated with a human ex-vivo culture model.•All treatments were able to reduce MERS-CoV replication.•The combined treatment was more effective than either agent used alone in reducing MERS-CoV replication.•The effect of the combined treatment group was associated with a greater induction of interferon stimulated genes.
Although Theory of Mind (ToM) impairment has been observed in patients with a wide range of mental disorders, the similarity and uniqueness of these deficits across diagnostic groups has not been ...thoroughly investigated.
We recruited 35 participants with schizophrenia (SCZ), 35 with bipolar disorder (BD), 35 with major depressive disorder (MDD), and 35 healthy controls in this study. All participants were matched in age, gender proportion and IQ estimates. The Yoni task, capturing both the cognitive and affective components of ToM at the first- and second-order level was administered. Repeated-measure ANOVA and MANOVA were conducted to compare the group differences in ToM performance. A network was then constructed with ToM performances, psychotic and depressive symptoms, and executive function as nodes exploring the clinical correlates of ToM.
Overall, ToM impairments were observed in all patient groups compared with healthy controls, with patients with SCZ performing worse than those with BD. In second-order conditions, patients with SCZ and MDD showed deficits in both cognitive and affective conditions, while patients with BD performed significantly poorer in cognitive conditions. Network analysis showed that second-order affective ToM performance was associated with psychotic and depressive symptoms as well as executive dysfunction, while second-order affective ToM performance and negative symptoms showed relatively high centrality in the network.
Patients with SCZ, MDD and BD exhibited different types and severity of impairments in ToM sub-components. Impairment in higher-order affective ToM appears to be closely related to clinical symptoms in both psychotic and affective disorders.
Purpose
To compare the peri-operative and long-term survival outcomes of minimally invasive liver resection (MILR) (robotic or laparoscopic) with open liver resection (OLR) in patients with ...hepatocellular carcinoma (HCC).
Methods
Data of patients who underwent liver resection for HCC were reviewed from a prospectively collected database. Outcomes of MILR were compared with those of OLR. A propensity score matching analysis with a ratio of 1:1 was performed to minimise the potential bias in clinical pathological factors.
Results
From January 2003 to December 2017, a total of 705 patients underwent liver resection for HCC. Amongst them, 112 patients received MILR and 593 patients received OLR. After propensity score matching, there were 112 patients in each of the MILR and OLR groups. Patients were matched by age, sex, hepatitis status, presence of cirrhosis, platelet count, albumin level, bilirubin level, alkaline phosphatase (ALP) level, alanine transferase (ALT) level, creatinine level, tumour differentiation, tumour size, tumour number, presence of tumour rupture, presence of vascular invasion, extent of liver resection (minor/major) and difficulty score. The 1-, 3- and 5-year overall survival rates were 94.4%, 90.4% and 82.3% in the MILR group vs 95.4%, 80.5% and 71.8% in the open group (
p
= 0.240). The 1-, 3- and 5-year disease-free survival rates were 81.0%, 63.1% and 55.8% in the MILR group vs 79.1%, 58.1% and 45.7 in the open group (
p
= 0.449). The MILR group demonstrated significantly less blood loss (
p
< 0.001), less blood transfusion (
p
= 0.004), lower post-operative complications (
p
< 0.001) and shorter hospital stay (
p
< 0.001) when compared with the OLR group.
Conclusions
Our data shows MILR yielded superior post-operative outcomes to OLR, with comparable survival outcomes.
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