Electronic brachytherapy for non-melanoma skin cancer in Asians: Experience from a Taiwan medical center.

BACKGROUND/PURPOSE: High-dose-rate (HDR) electronic brachytherapy (EBT) has been shown to be effective for non-melanoma skin cancer (NMSC) in Caucasian patients. However, its efficacy remains unknown in Asian patients. To analyze the clinical outcome of HDR EBT for NMSC in a Taiwanese medical center. METHODS: Medical records over a 5-year period between January 2015 to December 2019 were retrospectively analyzed. RESULTS: Forty-seven patients with 54 NMSC including 42 basal cell carcinomas (BCCs) and 12 squamous cell carcinomas (SCCs) were treated with HDR EBT. The average age was 73.8 years. The mean radiation dose was 45.3 Gy (40-80 Gy). Mean follow-up duration was 33.1 months. Adequate local control was achieved in 50 lesions (92.6%). Grade 1 acute skin toxicity was noted in 63.0% of lesions, while no tumors had Grade 4 acute toxicity. No ulceration was observed six months after completion of treatment. At the last follow-up visit, all lesions were rated to have "fair" to "excellent" cosmetic outcomes. CONCLUSION: HDR EBT provides adequate clinical outcomes and cosmetic results for NMSC in Asian patients. Further investigation of the dosage guidelines is needed for Asian patients with NMSC.

Association of ABCG2 rs2231142-A allele and serum uric acid levels in male and obese individuals in a Han Taiwanese population.

BACKGROUND/PURPOSE: Recent studies suggest that hyperuricemia is a potential risk factor for cardiovascular disease (CVD). Hyperuricemia is highly heritable and is associated with sex and body weight. Previous genome-wide association studies have found that the ABCG2 single nucleotide polymorphism (SNP) rs2231142 is an important genetic factor for increased uric acid (UA) levels, and the degree of association between rs2231142 and hyperuricemia is affected by both sex and ethnicity. This investigation aimed to analyze the association between ABCG2 polymorphisms and UA levels, as well as their interactions with sex and obesity in Taiwanese. METHODS: Two genetic polymorphisms around the ABCG2 gene were genotyped in 459 patients. RESULTS: After adjusting for clinical covariates, the rs2231142 SNP was found significantly associated with UA levels using a dominant inheritance model. Patients carrying the rs2231142-A allele had a higher frequency of hyperuricemia than those with the rs2231142-CC allele. Subgroup analysis revealed an association of rs2231142 with UA levels in male or obese patients, and there was no association in nonobese female patients. CONCLUSION: The rs2231142 SNP is associated with serum UA levels and hyperuricemia in Taiwanese patients and it occurs predominantly in male or obese patients. Hyperuricemia might be controlled differently by sex and obesity.

Outcomes of Endovascular Therapy With the Controlled Antegrade Retrograde Subintimal Tracking (CART) or Reverse CART Technique for Long Infrainguinal Occlusions.

PURPOSE: To compare the safety, efficacy, and clinical outcomes associated with the controlled antegrade retrograde subintimal tracking (CART) or reverse CART (r-CART) technique to the conventional retrograde approach in the treatment of patients with long infrainguinal occlusions. METHODS: From May 2008 to April 2014, 121 patients failed antegrade recanalization and underwent a retrograde approach to recanalize long infrainguinal occlusions. Patients who underwent successful endovascular therapy (EVT) by the conventional retrograde approach (CRA group) were compared to patients who had successful EVT using the CART/r-CART technique (CART group) after failure of a bidirectional approach. The efficacy, safety, vessel patency, and other clinical outcomes were compared between the groups. RESULTS: Fifty-eight patients (mean age 71.6 ± 12.2 years; 32 men) underwent successful EVT (47.9%, 58/121) using the conventional retrograde approach (CRA group), while 44 patients (mean age 70.8 ± 11.1 years; 31 men) among the 50 patients who underwent the CART/r-CART technique were successfully treated (88.0%, 44/50). Both groups had similar average occlusion lengths and gained 100% immediate hemodynamic success after EVT. There was no significant difference between the groups regarding procedure-related complications. During follow-up, 28 patients died (p=0.380), but there were no differences in the rates of major (p=0.279) or minor amputation (p=0.417) between the groups. There was no difference in the 2-year primary patency (31% vs 24%, p=0.686), assisted primary patency (66% vs 76%, p=0.251), target vessel revascularization (65% vs 54%, p=0.845), or sustained clinical success (52% vs 46%, p=0.995) rates between the CRA and CART groups, respectively. CONCLUSION: Based on acceptable safety, efficacy, and follow-up results in this study, the CART/r-CART technique can salvage patients with long peripheral occlusions after failure of the conventional antegrade or retrograde approach.

QT interval Independently Predicts Mortality and Heart Failure in Patients with ST-Elevation Myocardial Infarction.

OBJECTIVES: Heart-rate corrected QT (QTc) interval predicts cardiovascular mortality or all-cause mortality in the general population. Little is known about the best cut-off value of QTc interval for predicting clinical events in patients with ST-elevation myocardial infarction (STEMI). METHODS: We enrolled 264 patients with STEMI who received measurement of QTc intervals at ER (QTc-ER), on day 2 (QTc-D2), and on day 3 (QTc-D3) of hospitalization. Clinical events, including all-cause death and readmission for heart failure, were followed for 2 years. RESULTS: Prolonged QTc-ER, but not QTc-D2 or QTc-D3, well predicted clinical events with the best cut-off value of 445 ms. Patient with QTc-ER > 445 ms had lower left ventricular ejection fraction at baseline and at 6 months. Kaplan-Meier survival curves showed that the combination of QTc-ER > 445 ms and N-terminal pro-brain natriuretic peptide (NT-pro BNP) > 936 pg/mL was a strong predictor of clinical events (p<0.001). In multivariable Cox regression analysis, the independent predictors of death and heart failure were QTc-ER (p<0.001), log NT-proBNP (p<0.001), diabetes mellitus (p<0.001), history of stroke (p=0.001), and left ventricular end diastolic volume index (p<0.001). CONCLUSION: QTc-ER > 445 ms independently predicts clinical events in STEMI, providing incremental prognostic value to established clinical predictors and NT-proBNP.

Accordion Stent Deformation upon Retrieval of a Side-Branch Protective Guidewire.

UNLABELLED: In this case we herein report a dangerous complication from primary percutaneous coronary intervention, where an unnoticed loop of the guidewire was inadvertently made around the stent during provisional stenting. Since the guidewire and the stent were entangled, efforts to retrieve the guidewire only exacerbated the problem by compressing the stent like an accordion. We review those factors that may have influenced stent compression in our case, as well as possible ways to avoid it from occurring in the future. KEY WORDS: Catheterization; Coronary stenosis; Embolism; Myocardial infarction; Percutaneous coronary intervention; Stents.

Endovascular intervention in Taiwanese patients with critical limb ischemia: patient outcomes in 333 consecutive limb procedures with a 3-year follow-up.

BACKGROUND/PURPOSE: Midterm outcomes of endovascular intervention (EVI) for critical limb ischemia (CLI) have not been previously reported in Taiwan. This study assessed the safety, feasibility, and patient-oriented outcomes for CLI patients after EVI. METHODS: From June 2005 to December 2011, 270 patients underwent EVI for CLI of 333 limbs. Primary patency (PP), assisted primary patency (AP), limb salvage, sustained clinical success (SCS), secondary SCS (SSCS), and survival were assessed using Kaplan-Meier analysis. RESULTS: The procedural success rate was 89%, and the periprocedural mortality and major complication rates within 30 days were 0.6% and 6.9%, respectively. During the mean follow-up time of 27 ± 20 months (1-77), 64 patients died and 25 legs required major amputation. Eighty-one percent of the patients with tissue loss had wound healing at 6 months and 75% of the patients were ambulatory, with or without assisting devices, at 1 year. The overall survival and limb salvage rates at 3 years were 70% and 90%, respectively. The PP and AP at 1 and 3 years were 58% and 37% and 79% and 61%, respectively. The SCS and SSCS were 65% and 46% and 80% and 64% at 1 and 3 years, respectively. CONCLUSION: In Taiwan, EVI was a safe and feasible procedure for CLI patients, with a high procedural success rate and lower complication rate. Sustained limb salvage and clinical success can be afforded with an active surveillance program and prompt intervention during midterm follow-up.

Circulating YKL-40 level, but not CHI3L1 gene variants, is associated with atherosclerosis-related quantitative traits and the risk of peripheral artery disease.

YKL-40, a pleotropic cytokine, is emerging as a risk factor and a prognostic predictor of atherosclerotic cardiovascular disease. We attempted to elucidate the genetic, clinical and biochemical correlates of circulating YKL-40 level and, by combining it with CHI3L1 gene variants, with the risk and long-term mortality of peripheral artery disease (PAD). Plasma YKL-40 concentrations were measured in 612 Taiwanese individuals who had no clinically overt systemic disease. Clinical parameters, CHI3L1 gene promoter variants and 18 biomarker levels were analyzed. Eighty-six PAD patients were further enrolled for analysis. Significant associations were found between CHI3L1 genotypes/haplotypes and YKL-40 levels for the health examination subjects (smallest p = 8.36 × 10-7 for rs4950928 and smallest p = 1.72 × 10-10 for haplotype TGG) and also for PAD patients. For the health examination subjects, circulating YKL-40 level, but not CHI3L1 gene variants, were positively associated with age, smoking, and circulating levels of triglyceride, lipocalin 2 and multiple inflammatory biomarkers and negatively associated with low-density-lipoprotein cholesterol levels. Circulating YKL-40 level is also significantly associated with the risk of PAD (p = 3.3 × 10-23). Circulating YKL40 level, but not CHI3L1 gene promoter variants, is associated with the risk of PAD in Taiwanese. The association of YKL-40 levels with multiple quantitative traits relating to the risk of PAD may provide a molecular basis linking YKL-40 to atherosclerotic cardiovascular disease.

Is head and neck melanoma different from trunk and extremity melanomas with respect to sentinel lymph node status and clinical outcome?

BACKGROUND: Previous studies showed conflicting and inconsistent results regarding the effect of anatomic location of the melanoma on sentinel lymph node (SLN) positivity and/or survival. This study was conducted to evaluate and compare the effect of the anatomic locations of primary melanoma on long-term clinical outcomes. METHODS: All consecutive cutaneous melanoma patients (n=2,079) who underwent selective SLN dissection (SLND) from 1993 to 2009 in a single academic tertiary-care medical center were included. SLN positive rate, disease-free survival (DFS), and overall survival (OS) were determined. Kaplan-Meier survival, univariate, and multivariate analyses were performed to determine predictive factors for SLN status, DFS, and OS. RESULTS: Head and neck melanoma (HNM) had the lowest SLN-positive rate at 10.8% (16.8% for extremity and 19.3% for trunk; P=0.002) but had the worst 5-year DFS (P<0.0001) and 5-year OS (P<0.0001) compared with other sites. Tumor thickness (P<0.001), ulceration (P<0.001), HNM location (P=0.001), mitotic rate (P<0.001), and decreasing age (P<0.001) were independent predictive factors for SLN-positivity. HNM with T3 or T4 thickness had significantly lower SLN positive rate compared with other locations (P≤0.05). Also, on multivariate analysis, HNM location versus other anatomic sites was independently predictive of decreased DFS and OS (P<0.001). By Kaplan-Meier analysis, HNM was associated significantly with the worst DFS and OS. CONCLUSIONS: Primary melanoma anatomic location is an independent predictor of SLN status and survival. Although HNM has a decreased SLN-positivity rate, it shows a significantly increased risk of recurrence and death as compared with other sites.

Comparison of immediate and 2-year outcomes between excimer laser-assisted angioplasty with spot stent and primary stenting in intermediate to long femoropopliteal disease.

BACKGROUND: To compare the clinical outcomes between excimer laser-assisted angioplasty (ELA) with spot stent (group A) and primary stenting (group B) in intermediate to long femoropopliteal disease. METHODS: Outcomes of 105 patients totaling 119 legs treated with two different strategies were analyzed retrospectively in a prospectively maintained database. RESULTS: Baseline characteristics were similar in both groups. Better angiographic results and lesser increase of serum C-reactive protein levels (0.60 ± 0.72 versus 2.98 ± 0.97 mg/dL, P < 0.001) after the intervention were obtained in Group B. Group A had inferior 1-year outcomes due to higher rate of binary restenosis (67% versus 32%, P = 0.001) and lower rate of primary patency (40% versus 58%, P = 0.039). Rates of amputation-free survival, target vessel revascularization, assisted primary patency, and stent fracture at 24 months were similar in both groups (80% versus 82%, P = 0.979, 65% versus 45%, P = 0.11, 78% versus 80%, P = 0.75 and 6.3% versus 6.8%, P = 0.71, resp.). CONCLUSION: Greater vascular inflammation after ELA with spot stent resulted in earlier restenosis and inferior 1-year clinical outcomes than primary stenting. This benefit was lost in the primary stenting group at 2 years due to late catch-up restenosis. Active surveillance with prompt intervention was required to maintain the vessel patency.

The Genomic Landscape of Melanoma and Its Therapeutic Implications.

Melanoma is one of the most aggressive malignancies of the skin. The genetic composition of melanoma is complex and varies among different subtypes. With the aid of recent technologies such as next generation sequencing and single-cell sequencing, our understanding of the genomic landscape of melanoma and its tumor microenvironment has become increasingly clear. These advances may provide explanation to the heterogenic treatment outcomes of melanoma patients under current therapeutic guidelines and provide further insights to the development of potential new therapeutic targets. Here, we provide a comprehensive review on the genetics related to melanoma tumorigenesis, metastasis, and prognosis. We also review the genetics affecting the melanoma tumor microenvironment and its relation to tumor progression and treatment.

TRPM1 promotes tumor progression in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway.

INTRODUCTION: Acral melanoma is a predominant and aggressive subtype of melanoma in non-Caucasian populations. There is a lack of genotype-driven therapies for over 50% of patients. TRPM1 (transient receptor potential melastatin 1), a nonspecific cation channel, is mainly expressed in retinal bipolar neurons and skin. Nonetheless, the function of TRPM1 in melanoma progression is poorly understood. OBJECTIVES: We investigated the association between TRPM1 and acral melanoma progression and revealed the molecular mechanisms by which TRPM1 promotes tumor progression and malignancy. METHODS: TRPM1 expression and CaMKII phosphorylation in tumor specimens were tested by immunohistochemistry analysis and scored by two independent investigators. The functions of TRPM1 and CaMKII were assessed using loss-of-function and gain-of-function approaches and examined by western blotting, colony formation, cell migration and invasion, and xenograft tumor growth assays. The effects of a CaMKII inhibitor, KN93, were evaluated using both in vitro cell and in vivo xenograft mouse models. RESULTS: We revealed that TRPM1 protein expression was positively associated with tumor progression and shorter survival in patients with acral melanoma. TRPM1 promoted AKT activation and the colony formation, cell mobility, and xenograft tumor growth of melanoma cells. TRPM1 elevated cytosolic Ca2+ levels and activated CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) to promote the CaMKIIδ/AKT interaction and AKT activation. The functions of TRPM1 in melanoma cells were suppressed by a CaMKII inhibitor, KN93. Significant upregulation of phospho-CaMKII levels in acral melanomas was related to increased expression of TRPM1. An acral melanoma cell line with high expression of TRPM1, CA11, was isolated from a patient to show the anti-tumor activity of KN93 in vitro and in vivo. CONCLUSIONS: TRPM1 promotes tumor progression and malignancy in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway. CaMKII inhibition may be a potential therapeutic strategy for treating acral melanomas with high expression of TRPM1.

Osteoprotegerin and osteopontin levels, but not gene polymorphisms, predict mortality in cardiovascular diseases.

Aim: This study aims to investigate whether osteoprotegerin (OPG) or osteopontin (OPN) single nucleotide polymorphisms (SNPs) will predict survival. Materials & methods: This study enrolled 617 participants undergoing health examination, 536 coronary artery disease (CAD) patients and 86 peripheral artery disease (PAD) patients. Genotypes of OPG SNP rs2073618 and OPN SNP rs11730582 were determined. OPG and OPN levels were measured. Results: In both CAD and PAD populations, high OPG and OPN levels were strong predictors of all-cause death. The OPG rs2073618 CC genotype and the OPN rs11730582 TT genotype did not predict mortality. Conclusion: High OPG and high OPN levels, but not OPG rs2073618 CC genotype or OPN rs11730582 TT genotype, were strong predictors of mortality in both CAD and PAD patients.

Glaucoma is associated with peripheral vascular endothelial dysfunction.

PURPOSE: To evaluate peripheral vascular endothelial function in patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG) using noninvasive endothelium-dependent flow-mediated vasodilation (FMD). DESIGN: Case-control study. PARTICIPANTS: Thirty patients with NTG, 30 with POAG, and 30 healthy age- and gender-matched controls. METHODS: Participants underwent measurement of FMD and endothelium-independent nitroglycerin-mediated vasodilation (NMD) via high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. All patients also underwent blood sampling for biochemistry, lipid profile, and high sensitivity C-reactive protein analysis. MAIN OUTCOME MEASURES: The association of FMD with NTG and POAG. RESULTS: The FMD values differed significantly between the patients with NTG, those with POAG, and controls: NTG, 2.70+/-2.25%; POAG, 5.33+/-2.81%; controls, 7.21+/-2.36%; P<0.001. In comparison with the POAG group and normal controls, the NTG group demonstrated markedly impaired FMD. The POAG group exhibited higher intermediate FMD than the NTG group (P<0.001) but significantly lower FMD than normal controls (P = 0.012). Multivariate analysis indicated that independent predictors for impaired FMD were presence of NTG, presence of POAG, and advanced age. Additionally, FMD values were significantly lower in glaucoma patients than in controls (4.02+/-2.85% vs. 7.21+/-2.36%; P<0.001). CONCLUSIONS: Patients with glaucoma have impaired FMD. Additionally, patients with NTG have lower FMD than those with POAG.

Visual Subfield Progression in Glaucoma Subtypes.

PURPOSE: To investigate visual field progression pattern and factors associated with progression in patients with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and chronic angle-closure glaucoma (CACG). METHODS: The raw data of the 30-2 Humphrey Field Analyzer from glaucoma patients with definite visual field progression were processed with pointwise linear regression (PLR) analysis. The rate of change of retinal threshold sensitivity in the ten glaucoma hemifield test (GHT) zones, the upper and the lower hemifields, and the whole field was evaluated and was correlated with patients' basic demographic data. RESULTS: An average follow-up of 6.94 ± 2.69 years that showed the rate of change of visual field threshold sensitivity was correlated with the peak posttreatment intraocular pressure (IOP) and the long-term IOP fluctuations in all GHT zones except in the inferior arcuate area. The baseline IOP, the trough posttreatment IOP, the refractive status, and the CCT were not correlated with VF progression. CONCLUSION: The rate of visual field progression was correlated with the peak posttreatment IOP and the long-term IOP fluctuation but with subfield differences.

Secondary basal cell carcinoma of scalp after radiotherapy: A case report.

RATIONALE: Radiotherapy (RT) is widely used for both malignant and benign tumors in order to reduce the risk of recurrence, to promote tumor control, and to improve survival. However, there have been studies reported that RT is also a risk factor of secondary cancer. Very few cases of secondary malignancy after RT to high grade brain cancer have been reported due to short survival of this disease, and most RT-induced malignancies presented with sarcomatous histology. Here we present a patient with basal cell carcinoma (BCC) 14 years after RT to his brain. PATIENT CONCERNS: A 28-year-old man without any underlying disease had suffered from left side weakness and clonic-tonic seizures for 12 days. DIAGNOSES: His brain images showed a tumor in the right frontal lobe. The pathologic report confirmed anaplastic astrocytoma (WHO Grade III). INTERVENTIONS: After craniotomy and tumor biopsy, RT was delivered. Fourteen years later, a gray-colored skin papule was noted in the previously irradiated area. The scalp biopsy revealed BCC. The scalp BCC was adequately resected. He then suffered from brain tumor recurrence and received further craniotomy for three times combined with chemotherapy with temozolomide. OUTCOMES: After treatment, follow-up brain images showed that the disease was under control. There was no neurological sequela. For scalp BCC, no skin tumor recurrence has been noted to date after the resection 14 years after initial RT. He has survived for more than 26 years since his initial diagnosis of anaplastic astrocytoma, and more than 12 years from the diagnosis of scalp BCC. LESSONS: Notwithstanding the risk of radiation-induced skin cancer, RT contributed to this patient's survival. The possible late adverse events should be informed to the patients.