Aims: The aim of this study was to compare the outcomes of radiofrequency thermal ablation (RFTA), percutaneous ethanol injection (PEI), and percutaneous acetic acid injection (PAI) in the treatment ...of hepatocellular carcinoma (HCC). Patients and methods: A total of 187 patients with HCCs of 3 cm or less were randomly assigned to RFTA (n = 62), PEI (n = 62), or PAI (n = 63). Tumour recurrence and survival rates were assessed. Results: One, two, and three year local recurrence rates were 10%, 14%, and 14% in the RFTA group, 16%, 34%, and 34% in the PEI group, and 14%, 31%, and 31% in the PAI group (RFTA v PEI, p = 0.012; RFTA v PAI, p = 0.017). One, two, and three year survival rates were 93%, 81%, and 74% in the RFTA group, 88%, 66%, and 51% in the PEI group, and 90%, 67%, and 53% in the PAI group (RFTA v PEI, p = 0.031; RFTA v PAI, p = 0.038). One, two, and three year cancer free survival rates were 74%, 60%, and 43% in the RFTA group, 70%, 41%, and 21% in the PEI group, and 71%, 43%, and 23% in the PAI group (RFTA v PEI, p = 0.038; RFTA v PAI, p = 0.041). Tumour size, tumour differentiation, and treatment methods (RFTA v PEI and PAI) were significant factors for local recurrence, overall survival, and cancer free survival. Major complications occurred in 4.8% of patients (two with haemothorax, one gastric perforation) in the RFTA group and in none in two other groups (RFTA v PEI and PAI, p = 0.035). Conclusions: RFTA was superior to PEI and PAI with respect to local recurrence, overall survival, and cancer free survival rates, but RFTA also caused more major complications.
Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine ...degrading enzyme—arginine deiminase—conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy.
Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4–5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives.
A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion.
ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway.
www.clinicaltrials.gov (NCT 01287585).
The open-cell porous Ti-6Al-4V structure, intended to be applied as replacement for human cortical and cancellous bone, are fabricated by selective laser melting (SLM). The computer aided design ...(CAD) was used to design porous structures in various porosity levels from 40% to 80% and with pore sizes from 600 to 1000 μm, in order to fit the bone-tissue in-growth. The SLM porous samples with 40% to 70% porosity matched well with the CAD structure, but the 80% porosity one was found to be difficult to achieve the design. In comparison with the CAD structures and the SLM samples, there are minor discrepancies in terms of pore size and ligament width, mainly a result of laser beam broadening. To achieve more precise SLM porous morphologies, further reduction of powder size and laser beam diameter would be necessary. The measured data on the Young's modulus and yield strength of the SLM porous samples can be roughly estimated by the Gibson and Ashby model. The sample with 67% porosity was found to match best with human bone, with Young's modulus of 15 GPa and yield stress of 129 MPa, preventing from the risk of stress shielding effect.
•The porous Ti-6Al-4V foams are prepared by selective laser melting.•Minor discrepancies between CAD and SLM are due to laser beam broadening.•The 67% porosity sample matches with human bone avoiding stress shielding effect.
Summary
Background
Few large population‐based studies have compared the occurrence of peptic ulcer bleeding (PUB) in cirrhotic and noncirrhotic patients.
Aims
To investigate if cirrhotic patients ...have higher risk of PUB than the general population and to identify possible risk factors of PUB in cirrhotic patients.
Methods
Using the National Health Insurance Research Database, a nationwide population‐based dataset in Taiwan and matching age, gender, comorbidities and ulcerogenic medication by propensity score, 4013 cirrhotic patients, 8013 chronic hepatitis patients and 7793 normal controls were compared. The log‐rank test was used to analyse differences in accumulated PUB‐free survival rates between the groups. Cox proportional hazard regressions were performed to evaluate independent risk factors for PUB in all patients and identified risk factors of PUB in cirrhotic patients.
Results
During the 7‐year follow‐up, cirrhotic patients had significantly higher incidences of PUB than chronic hepatitis patients and controls, respectively (P < 0.001 by log‐rank test). By Cox proportional hazard regression analysis, cirrhosis was independently associated with increased risk of PUB (hazard ratio: 4.22; 95% CI 3.37–5.29, P < 0.001) after adjusting for age, gender, economic status, underlying comorbidities and ulcerogenic medication. Age, male, diabetes, chronic renal disease, history of gastro‐oesophageal variceal bleeding and use of nonsteroidal anti‐inflammatory drugs were risk factors for PUB in cirrhotic patients.
Conclusion
Cirrhotic patients have a significantly higher risk of peptic ulcer bleeding after adjustments for possible confounding factors like age, gender, economic status, underlying comorbidities and ulcerogenic medication.
Objective
To investigate the expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer (DFU) and its effect on angiogenesis in DFU rats.
Methods
The serum levels of miR-217, ...HIF-1α and VEGF were detected in DFU and simple diabetes mellitus (DM) patients, and healthy controls. DFU rat models were established and treated with miR-217 inhibitors and/or HIF-1α siRNA. The ulcer healing of DFU rats was observed. Besides, ELISA method was performed to detect the serum level of HIF-1α, VEGF and inflammatory factors, immunohistochemical (IHC) method to test the micro-vessel density (MVD), as well as qRT-PCR and Western blot to determine expressions of miR-217, HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 in tissues.
Results
The serum levels of miR-217 were up-regulated while HIF-1α and VEGF were down-regulated in DFU patients and rats when compared with DM and healthy controls (all
P
< 0.05). Dual-luciferase reporter gene assay confirmed that
HIF
-
1α
was the direct target gene of miR-217. DFU rats treated with miR-217 inhibitors had decreased foot ulcer area and accelerated ulcer healing, with significantly reduced inflammatory factors (IL-1β, TNF-α and IL-6), as well as elevated HIF-1α and VEGF (all
P
< 0.05); meanwhile, they remarkably increased the MVD in foot dorsum wound tissues and the protein expressions of HIF-1α, VEGF, VEGFR2, eNOS, MMP-2, and MMP-9 (all
P
< 0.05).
Conclusion
Inhibiting miR-217 could up-regulate HIF-1α/VEGF pathway to promote angiogenesis and ameliorate inflammation of DFU rats, thereby effectively advancing the healing of ulcerated area.
Summary
The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated ...with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile.
Introduction
This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis.
Methods
Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively.
Results
Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed.
Conclusions
Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.
Summary
Esophagitis is the second most common gastrointestinal manifestation of cytomegalovirus (CMV) infection after colitis. CMV esophagitis has been reported in patients who have undergone ...transplantation, are on long‐term renal dialysis, or who have the human immunodeficiency virus infection. This study aimed to investigate the clinical characteristics and manifestations of CMV esophagitis in patients who underwent diagnostic endoscopy. A total of 16 patients with histologically proven CMV infection were identified from 1539 patients with esophageal ulcers and analyzed retrospectively (January 2006 to December 2013). Patients' personal data (age, smoking, and alcohol consumption), underlying systemic diseases (diabetes mellitus, end‐stage renal disease, and chronic obstructive pulmonary disease), malignancy, indication for esophagogastroduodenoscopy, endoscopic characteristics, and diagnostic methods (pathological or serological findings) were collected for further analysis. Among the patients with CMV esophagitis, the mean age was 59.94 years (range, 23–84 years). The male : female ratio was 1.67:1. Odynophagia and epigastralgia were common symptoms. Of the 16 patients, 3 (18.75%) were infected with the human immunodeficiency virus and 9 (56.25%) had an underlying malignancy, including lung cancer (6 patients), esophageal cancer (2 patients), gastric cancer (1 patient), ampulla of Vater cancer (1 patient), and lymphoma (1 patient). Six of the 9 patients (66.7%) with malignancy had been administered concurrent chemoradiotherapy (CCRT). In this study, patients with malignancy who had been administered CCRT were at increased risk for CMV esophagitis, which had not been reported before in the literature. CMV esophagitis should be considered as a potential treatment‐related complication of CCRT.
Background
Postoperative colorectal anastomotic strictures are quite common. As such, many techniques have been available to address such a problem, one of which is endoscopic dilation. The aim of ...the present study was to evaluate the long-term outcomes following endoscopic dilation using a multidiameter balloon.
Methods
A retrospective study was conducted on patients with postoperative anastomotic stenosis treated with endoscopic dilation using a multidiameter balloon at our institution, in January 2005–December 2019 were retrospectively reviewed, excluding those with tumor recurrence. Perioperative factors, complications, and recurrence rates were analyzed.
Results
There were 40 patients, (22 males and 18 females, mean age 64.6 ± 10.7 years, range 33–84 years). The median follow-up period was 56 months (interquartile range 22.5–99 months). Only 1 complication occurred, micro-perforation due to guided wire injury, which was managed conservatively. Five (12.5%) patients developed restenosis and underwent repeat balloon dilation. None of the five recurrences required more aggressive management, such as redo anastomosis.
Conclusions
Endoscopic multidiameter balloon dilation is a safe and effective method for treating benign colorectal anastomotic strictures.
Sinus stenosis occasionally occurs in dural arteriovenous fistulas. Sinus stenosis impedes venous outflow and aggravates intracranial hypertension by reversing cortical venous drainage. This study ...aimed to analyze the likelihood of sinus stenosis and its impact on cerebral hemodynamics of various types of dural arteriovenous fistulas.
Forty-three cases of dural arteriovenous fistula in the transverse-sigmoid sinus were reviewed and divided into 3 groups: Cognard type I, type IIa, and types with cortical venous drainage. Sinus stenosis and the double peak sign (occurrence of 2 peaks in the time-density curve of the ipsilateral drainage of the internal jugular vein) in dural arteriovenous fistula were evaluated. "TTP" was defined as the time at which a selected angiographic point reached maximum concentration. TTP of the vein of Labbé, TTP of the ipsilateral normal transverse sinus, trans-fistula time, and trans-stenotic time were compared across the 3 groups.
Thirty-six percent of type I, 100% of type IIa, and 84% of types with cortical venous drainage had sinus stenosis. All sinus stenosis cases demonstrated loss of the double peak sign that occurs in dural arteriovenous fistula. Trans-fistula time (2.09 seconds) and trans-stenotic time (0.67 seconds) in types with cortical venous drainage were the most prolonged, followed by those in type IIa and type I. TTP of the vein of Labbé was significantly shorter in types with cortical venous drainage. Six patients with types with cortical venous drainage underwent venoplasty and stent placement, and 4 were downgraded to type IIa.
Sinus stenosis indicated dysfunction of venous drainage and is more often encountered in dural arteriovenous fistula with more aggressive types. Venoplasty ameliorates cortical venous drainage in dural arteriovenous fistulas and serves as a bridge treatment to stereotactic radiosurgery in most cases.
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