Current guidelines recommend surgical resection as the primary treatment for a single hepatocellular cancer (HCC) with Child's A cirrhosis, normal serum bilirubin, and no clinically significant portal hypertension. We determined how frequently guidelines were followed and whether straying from them impacted survival. BRIDGE is a multiregional cohort study including HCC patients diagnosed between January 1, 2005 and June 30, 2011. A total of 8,656 patients from 20 sites were classified into four groups: (A) 718 ideal resection candidates who were resected; (B) 144 ideal resection candidates who were not resected; (C) 1,624 nonideal resection candidates who were resected; and (D) 6,170 nonideal resection candidates who were not resected. Median follow‐up was 27 months. Log‐rank and Cox's regression analyses were conducted to determine differences between groups and variables associated with survival. Multivariate analysis of all ideal candidates for resection (A+B) revealed a higher risk of mortality with treatments other than resection. For all resected patients (A+C), portal hypertension and bilirubin >1 mg/dL were not associated with mortality. For all patients who were not ideal candidates for resection (C+D), resection was associated with better survival, compared to embolization and “other” treatments, but was inferior to ablation and transplantation. Conclusions: The majority of patients undergoing resection would not be considered ideal candidates based on current guidelines. Not resecting ideal candidates was associated with higher mortality. The study suggests that selection criteria for resection may be modestly expanded without compromising outcomes, and that some nonideal candidates may still potentially benefit from resection over other treatment modalities. (Hepatology 2015;62:440–451

Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). Conclusions: In this study, brivanib as adjuvant therapy to TACE did not improve OS. (HEPATOLOGY 2014;60:1697-1707

This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade 3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.

Transarterial chemoembolization (TACE) represents a first-line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.Hepatocellular carcinoma (HCC) is fifth most common cancer worldwide 1 but has a very uneven geographic distribution. South-east Asian countries and tropical Africa show the highest incidence with peak rates of 150 per 100,000 in Taiwan 2 and 28 per 100,000 in Singapore. 3 Over 600,000 new cases of liver cancer are diagnosed globally each year, 1 and the Asia-Pacific regions contribute more than 50% of these. The lowest rates are found in western countries, Australia,

Although the risks of microplastics in environmental exposure and human health are being increasingly studied, little is known about the behavior of "eco-friendly" bioplastics in humans, especially their effects on our gastrointestinal tract. Here we demonstrate that enzymatic hydrolysis of bio-based polylactic acid (PLA) microplastics rapidly generates an excess of nanoplastic particles by competing for triglyceridedegrading lipase during gastrointestinal processes. These tiny nanoparticles are oligomers formed by hydrophobic-driven self-aggregation, and upon exposure the oligomers and their associated nanoparticles can bioaccumulate in in vitro and several in vivo organs, including the liver, intestine, and even in the brain. Severe intestinal damage and in ammation are also observed, the toxic effect of which is mostly pronounced from hydrolyzed oligomer products. Furthermore, the oligomers' potential protein target screening using large scale pharmacophore model reveals that oligomers can interact with matrix metallopeptidase 12 protein (MMP12), which is further validated using protein binding assay. A close mechanistic study reveals high binding a nity of oligomers to the catalytic zinc ion nger domain, leading to MMP12 inactivation and mediating the adverse bowel in ammatory effect following PLA oligomer exposure. Since biodegradable plastics are highly proposed as one solution for the global plastic problem, understanding the gastrointestinal fate and toxicity of bioplastics, will provide groundbreaking data on bioplastics as a substantial risk to human health.

We herein present a case involving a 41-year-old woman in whom ultrasound examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up ultrasound examination revealed that the masses had significantly increased; the largest was located in the right lobe (about 8.2 cm × 7.4 cm × 6.0 cm). Abdominal multidetector computed tomography revealed multiple well-circumscribed, heterogeneous, hypodense masses (largest, 6.4 cm × 6.3 cm × 5.0 cm) with significant contrast enhancement during the arterial and portal phases and with contrast wash-out and peripheral enhancement during the delayed phases. Magnetic resonance images demonstrated multiple well-circumscribed, heterogeneous, hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm × 6.5 cm × 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly enlarged retroperitoneal lymph nodes. Histological and immunohistochemical examination of the right mass biopsy specimen suggested a malignant neoplasm that had originated from a neuroendocrine cell type (grade 2 well-differentiated neuroendocrine carcinoma). After performing a systemic examination to exclude metastasis from an extrahepatic primary site, we considered that the masses had arisen from a primary hepatic neuroendocrine tumor with multiple liver metastases. The patient underwent transcatheter arterial chemoembolization using a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge particles (560-710 μm) and lipiodol (6 mL). Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously reported cases in the literature are also reviewed.

offers a low-cost solution for high-speed interconnects for data transmission. The integration of high-quality direct-bandgap III-V lasers on Si platform is a core technology for achieving high-performance Si-based III-V optoelectronic devices, [1-3] due to the inefficient light-emitting properties of Group-IV materials. [4,5] Currently, the realization of III-V lasers on Si mainly relies on either wafer bonding or monolithic growth techniques, with the latter method being more favorable for low cost, high yield and large-scale production. [6,7] Nevertheless, the large lattice mismatch, different polarities and incompatible thermal expansion coefficients between III-V materials and Si induce various crystal defects during the epitaxial growth such as threading dislocations (TDs), inversion boundaries (IBs, often called anti-phase boundaries, APBs), and microcracks. [8-13] These defects act as non-radiative recombination centers and significantly hinder the performance of optoelectronic devices in terms of lifetime, threshold operating power and temperature performance. [2,7,14] Approaches including strained-layer superlattice (SLS) acting as a defect filter layer (DFL) and a longer cool-down period after growth were implemented to sufficiently suppress TDs and micro-cracks, respectively. [12,13,15] By contrast, IBs are electrically charged planar Monolithic integration of III-V materials and devices on CMOS compatible on-axis Si (001) substrates enables a route of low-cost and high-density Si-based photonic integrated circuits. Inversion boundaries (IBs) are defects that arise from the interface between III-V materials and Si, which makes it almost impossible to produce high-quality III-V devices on Si. In this paper, a novel technique to achieve IB-free GaAs monolithically grown on on-axis Si (001) substrates by realizing the alternating straight and meandering single atomic steps on Si surface has been demonstrated without the use of double Si atomic steps, which was previously believed to be the key for IB-free III-V growth on Si. The periodic straight and meandering single atomic steps on Si surface are results of high-temperature annealing of Si buffer layer. Furthermore, an electronically pumped quantum-dot laser has been demonstrated on this IB-free GaAs/Si platform with a maximum operating temperature of 120 °C. These results can be a major step towards monolithic integration of III-V materials and devices with the mature CMOS technology.

BackgroundPrimary hepatic neuroendocrine carcinomas (PHNECs) are rare and asymptomatic, and are therefore difficult to distinguish radiologically from other liver carcinomas. In this study, we aimed to determine the computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) features of PHNECs.MethodsA retrospective analysis of 11 patients with pathologically proven PHNECs was performed from January 2009 to September 2014. The CT, MRI, and DSA image features were analysed.ResultsTen of the eleven patients exhibited two or more lesions, and one patient exhibited a single lesion. Abdominal CT of 8 cases revealed multiple round or oval-shaped masses with well-defined borders, which were heterogeneous and hypodense on precontrast CT images. Significant diffuse heterogeneous enhancement was observed during the arterial phase in 8 cases, and the enhancement was slightly higher than the attenuation of the surrounding normal liver parenchyma and indistinct edges of small lesions during the portal phase. Well circumscribed (11 cases), lobulated (5 cases) or multiple nodular masses (4 cases), nodule (1 case) and irregular masses (1 case) of high signal intensity were observed on T2WI and DWI of MR images. The masses were well circumscribed, heterogeneous, and hypointense on T1WI, with significant enhancement of the solid carcinoma portion in the early arterial phase and continued enhancement in the portal venous phase. Characteristic lobulated or multiple nodular masses were observed in MRI. DSA showed multiple hypervascular carcinoma-staining lesions with sharp edges in the arterial phase.ConclusionThe CT, MRI, and DSA images of PHNECs exhibit specific characteristic features. Appropriate combinations of the available imaging modalities could therefore optimize the evaluation of patients with PHNECs.