Hepatocellular carcinoma detected by regular surveillance: Does timely confirmation of diagnosis matter?

AbstractBackgroundAlthough current guidelines recommended surveillance of hepatocellular carcinoma, prognosis in patients undergoing enhanced follow-up has yet to be evaluated.AimsExamine outcomes of hepatocellular carcinoma diagnosed during enhanced follow-up.MethodsDuring 2010–2012, 194 patients underwent ultrasonography surveillance were diagnosed with hepatocellular carcinoma and divided into: (A) immediate diagnosis (N=105, 54.1%) after positive ultrasonography, (B) enhanced follow-up: (N=38, 19.6%) for initial negative recall procedures, (C) late call back: (N=28, 14.4%) recall procedures were deferred after positive ultrasonography, and (D) beyond ultrasonography: (N=23, 11.9%) surveillance ultrasonography had been negative.ResultsMedian time from positive ultrasonography to confirmation of hepatocellular carcinoma were 9.5 months (2–67) in the Group B and 6.5 months (3–44) in the Group C. Stage distribution and 3-year survival rates were similar amongst all Groups. Surveillance intervals longer than 6 months were associated with the non-curative stage (3.7% vs. 12.5%, p=0.04). Nine (4.6%) patients underwent surveillance were diagnosed as Barcelona-Clinic Liver Cancer stage C.ConclusionEnhanced follow-up by current guidelines is appropriate that treatment can be deferred until a definite diagnosis. Despite optimal surveillance interval and recall policies, few non-curative stage diagnoses seemed inevitable under current standard of care

Pituitary macroadenoma co-existent with supraclinoid internal carotid artery cerebral aneurysm: a case report and review of the literature

With improved angiographic techniques and magnetic resonance angiography available today, an increasing number of incidental aneurysms are being detected. Occurrence of an intracranial aneurysm together with a pituitary adenoma presents tremendous risk to the patient, particularly when the aneurysm lies near the operative field

Acute Paraparesis Caused by a Giant Cell Tumor of the Thoracic Spine

AbstractGiant cell tumor (GCT) is a benign but locally aggressive skeletal neoplasm of young adults. GCT located in the spine is relatively rare and may need a combination of surgical and adjunctive therapies. Here we present a patient who had intermittent thoracic back pain for two weeks and experienced an acute episode of decreased muscle power of both lower limbs. Magnetic resonance (MR) imaging examinations of the thoracic spine revealed that the patient had severe spinal canal compression caused by pathological fracture due to a tumor within the seventh thoracic vertebra. She underwent an emergent surgical intervention for total removal of the tumor and spinal reconstruction with autologous rib grafts and instruments. Postoperatively, the patient made an uneventful recovery of muscle power of bilateral lower limbs. She subsequently received adjuvant radiotherapy. In a follow-up period of 36 months, the patient had no clinical or radiological evidence of tumor recurrence. Even though spinal location for GCT is a rare event, it should be included in the differential diagnosis in patients with osteolytic lesions or pathological fractures of the vertebra, especially in young female patients sustaining no trauma who had a clinical history of persistent low back pain

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation

BACKGROUND: Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. OBJECTIVES: The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. METHODS: Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. RESULTS: At the cutoff values of eGFR of 50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as “on label” based on MDRD or CKD-EPI, only those whose dosages were “truly on label” based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin. CONCLUSIONS: The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients

Background The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation. Results We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038). Conclusions ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients

Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

Objective Patients with hyperthyroidism were excluded from randomized clinical trials of direct oral anticoagulants(DOACs) for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3,213 and 1,181 NVAF patients with hyperthyroidism taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53,591 and 16,564 NVAF patients without hyperthyroidism taking DOACs and warfarin, respectively. We used propensity score-based stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n=3,213) and without hyperthyroidism (n=12,852); and both taking warfarin, with (n=1,181) and without hyperthyroidism (n=4,724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio (HR):0.65; [95% confidential interval (CI):0.44-0.96]; P=0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, patients taking warfarin with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR:0.61; [95%CI:0.43-0.86]; P=0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.Supplemental materials (figures and tables) for the article of "Direct Oral Anticoagulants in Atrial Fibrillation Patients with Concomitant Hyperthyroidism" Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3G1371-3Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3F0991-3Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPD1K0031Funding provided by: Chang Gung Memorial HospitalCrossref Funder Registry ID: http://dx.doi.org/10.13039/100012553Award Number: CMRPG3K0021We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3,213 and 1,181 NVAF patients with hyperthyroidism taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017

Leukocyte Cell-Derived Chemotaxin 2 Retards Non-Small Cell Lung Cancer Progression Through Antagonizing MET and EGFR Activities

Background/Aims: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy is a clinical option for non-small cell lung cancer (NSCLC) harboring activating EGFR mutations or for cancer with wild-type (WT) EGFR when chemotherapy has failed. MET receptor activation or MET gene amplification was reported to be a major mechanism of acquired resistance to EGFR-TKI therapy in NSCLC cells. Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that was shown to suppress metastasis of hepatocellular carcinoma via inhibiting MET activity. Until now, the biological function responsible for LECT2’s action in human NSCLC remains unclear. Methods: LECT2-knockout (KO) mice and NOD/SCID/IL2rgnull (NSG) mice were respectively used to investigate the effects of LECT2 on the tumorigenicity and metastasis of murine (Lewis lung carcinoma, LLC) and human (HCC827) lung cancer cells. The effect of LECT2 on in vitro cell proliferation was evaluated, using MTS and colony formation assays. The effect of LECT2 on cell motility was evaluated using transwell migration and invasion assays. An enzyme-linked immunosorbent assay was performed to detect secreted LECT2 in plasma and media. Co-immunoprecipitation and Western blot assays were used to investigate the underlying mechanisms of LECT2 in NSCLC cells. Results: Compared to WT mice, mice with LECT2 deletion exhibited enhanced growth and metastasis of LLC cells, and survival times decreased in LLC-implanted mice. Overexpression of LECT2 in orthotopic human HCC827 xenografts in NSG mice resulted in significant inhibition of tumor growth and metastasis. In vitro, overexpression of LECT2 or treatment with a recombinant LECT2 protein impaired the colony-forming ability and motility of NSCLC cells (HCC827 and PC9) harboring high levels of activated EGFR and MET. Mechanistic investigations found that LECT2 bound to MET and EGFR to antagonize their activation and further suppress their common downstream pathways: phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase. Conclusion: EGFR-MET signaling is critical for aggressive behaviors of NSCLC and is recognized as a therapeutic target for NSCLC especially for patients with acquired resistance to EGFR-TKI therapy. Our findings demonstrate, for the first time, that LECT2 functions as a suppressor of the progression of NSCLC by targeting EGFR-MET signaling

Carrier Screening for Spinal Muscular Atrophy (SMA) in 107,611 Pregnant Women during the Period 2005–2009: A Prospective Population-Based Cohort Study

BACKGROUND: Spinal muscular atrophy (SMA) is the most common neuromuscular autosomal recessive disorder. The American College of Medical Genetics has recently recommended routine carrier screening for SMA because of the high carrier frequency (1 in 25-50) as well as the severity of that genetic disease. Large studies are needed to determine the feasibility, benefits, and costs of such a program. METHODS AND FINDINGS: This is a prospective population-based cohort study of 107,611 pregnant women from 25 counties in Taiwan conducted during the period January 2005 to June 2009. A three-stage screening program was used: (1) pregnant women were tested for SMA heterozygosity; (2) if the mother was determined to be heterozygous for SMA (carrier status), the paternal partner was then tested; (3) if both partners were SMA carriers, prenatal diagnostic testing was performed. During the study period, a total of 2,262 SMA carriers with one copy of the SMN1 gene were identified among the 107,611 pregnant women that were screened. The carrier rate was approximately 1 in 48 (2.10%). The negative predictive value of DHPLC coupled with MLPA was 99.87%. The combined method could detect approximately 94% of carriers because most of the cases resulted from a common single deletion event. In addition, 2,038 spouses were determined to be SMA carriers. Among those individuals, 47 couples were determined to be at high risk for having offspring with SMA. Prenatal diagnostic testing was performed in 43 pregnant women (91.49%) and SMA was diagnosed in 12 (27.91%) fetuses. The prevalence of SMA in our population was 1 in 8,968. CONCLUSION: The main benefit of SMA carrier screening is to reduce the burden associated with giving birth to an affected child. In this study, we determined the carrier frequency and genetic risk and provided carrier couples with genetic services, knowledge, and genetic counseling