Enhancing the Contouring Efficiency for Head and Neck Cancer Radiotherapy Using Atlas-based Auto-segmentation and Scripting.

BACKGROUND/AIM: Intensity-modulated radiation therapy can deliver a highly conformal dose to a target while minimizing the dose to the organs at risk (OARs). Delineating the contours of OARs is time-consuming, and various automatic contouring software programs have been employed to reduce the delineation time. However, some software operations are manual, and further reduction in time is possible. This study aimed to automate running atlas-based auto-segmentation (ABAS) and software operations using a scripting function, thereby reducing work time. MATERIALS AND METHODS: Dice coefficient and Hausdorff distance were used to determine geometric accuracy. The manual delineation, automatic delineation, and modification times were measured. While modifying the contours, the degree of subjective correction was rated on a four-point scale. RESULTS: The model exhibited generally good geometric accuracy. However, some OARs, such as the chiasm, optic nerve, retina, lens, and brain require improvement. The average contour delineation time was reduced from 57 to 29 min (p<0.05). The subjective revision degree results indicated that all OARs required minor modifications; only the submandibular gland, thyroid, and esophagus were rated as modified from scratch. CONCLUSION: The ABAS model and scripted automation in head and neck cancer reduced the work time and software operations. The time can be further reduced by improving contour accuracy.

Calyceal Diverticulum Found Incidentally on 18 F-FDG PET/CT Imaging.

ABSTRACT: A 69-year-old man with pancreatic cancer underwent 18 F-FDG PET/CT examination for tumor staging. The PET images showed a focal mass-like FDG accumulation in the left kidney mimicking malignancy, whereas simultaneous CT and fused PET/CT images suggested a cystic lesion. On subsequent MR examination, the lesion appeared cystic on T2-weighted, contrast-enhanced arterial phase, and contrast-enhanced venous phase images. In addition, excretory phase images showed filling contrast medium to the cystic cavity, leading to a diagnosis of calyceal diverticulum. This report suggests that the possibility of a calyceal diverticulum should be considered in cases with focal FDG accumulation in renal cystic lesions.

Reduced ER-mitochondrial contact sites and mitochondrial Ca2+ flux in PRKN-mutant patient tyrosine hydroxylase reporter iPSC lines.

Endoplasmic reticulum-mitochondrial contact sites (ERMCS) play an important role in mitochondrial dynamics, calcium signaling, and autophagy. Disruption of the ERMCS has been linked to several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, the etiological role of ERMCS in these diseases remains unclear. We previously established tyrosine hydroxylase reporter (TH-GFP) iPSC lines from a PD patient with a PRKN mutation to perform correlative light-electron microscopy (CLEM) analysis and live cell imaging in GFP-expressing dopaminergic neurons. Here, we analyzed ERMCS in GFP-expressing PRKN-mutant dopaminergic neurons from patients using CLEM and a proximity ligation assay (PLA). The PLA showed that the ERMCS were significantly reduced in PRKN-mutant patient dopaminergic neurons compared to the control under normal conditions. The reduction of the ERMCS in PRKN-mutant patient dopaminergic neurons was further enhanced by treatment with a mitochondrial uncoupler. In addition, mitochondrial calcium imaging showed that mitochondrial Ca2+ flux was significantly reduced in PRKN-mutant patient dopaminergic neurons compared to the control. These results suggest a defect in calcium flux from ER to mitochondria is due to the decreased ERMCS in PRKN-mutant patient dopaminergic neurons. Our study of ERMCS using TH-GFP iPSC lines would contribute to further understanding of the mechanisms of dopaminergic neuron degeneration in patients with PRKN mutations.

Increased toxicities associated with dose escalation of stereotactic body radiation therapy in prostate cancer: results from a phase I/II study.

BACKGROUND: This dose-escalation study evaluated the toxicity and efficacy of different stereotactic body radiation therapy (SBRT) doses for selecting an optimal dose for prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: This clinical trial was registered at UMIN (UMIN000014328). Patients with low- or intermediate-risk PCa were equally assigned to 3 SBRT dose levels: 35, 37.5, and 40 Gy per 5 fractions. The primary endpoint was the occurrence rate of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events at 2 years, while the secondary endpoint was the 2-year biochemical relapse-free (bRF) rate. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Seventy-five patients (median age, 70 years) were enrolled from March 2014 to January 2018, of whom 10 (15%) and 65 (85%) had low- and intermediate-risk PCa, respectively. The median follow-up time was 48 months. Twelve (16%) patients received neoadjuvant androgen deprivation therapy. The 2-year occurrence rates of grade 2 late GU and GI toxicities were 34 and 7% in all cohorts, respectively (35 Gy: 21 and 4%; 37.5 Gy: 40 and 14%; 40 Gy: 42 and 5%). The occurrence risk of GU toxicities significantly increased with dose escalation (p = 0.0256). Grades 2 and 3 acute GU toxicities were observed in 19 (25%) and 1 (1%), respectively. Grade 2 acute GI toxicity was observed in 8 (11%) patients. No grade ≥3 GI or ≥4 GU acute toxicity or grade ≥3 late toxicity was observed. Clinical recurrence was detected in 2 patients. CONCLUSIONS: An SBRT dose of 35 Gy per 5 fractions is less likely to cause adverse events in patients with PCa than 375- and 40-Gy SBRT doses. Higher doses of SBRT should be applied with caution.

Monitoring expiratory carbon monoxide to study the effect of complete smoking cessation on definitive radiation therapy for early stage glottic carcinoma.

BACKGROUND: Previous studies reported that cigarette smoking during radiation therapy was associated with unfavorable outcomes in various cancers using medical interviewing or monitoring of cotinine. Here, we evaluated the effect of smoking cessation on definitive radiation therapy for early stage glottic carcinoma by monitoring expiratory carbon monoxide (CO). MATERIAL AND METHODS: We enrolled 103 patients with early glottic carcinoma (T1N0/T2N0 = 79/24) who underwent conventional radiotherapy between 2005 and 2016. The median age was 70 years. Pathologically, all patients had squamous cell carcinoma. Since 2009, we confirmed smoking cessation before radiation therapy by medical interviews. Since 2014, we measured expiratory CO to strictly monitor smoking cessation. The patients were divided according to diagnosis years: 'no cessation' (2005-2008), 'incomplete cessation' (2009-2013), and 'complete cessation' (2014-2016). We retrospectively analyzed the local recurrence rate and disease-free survival (DFS). RESULTS: The median follow-up period was 60.1 months (range, 1.9-110.0 months). The 2-year local recurrence rate in the 'complete cessation' group was 5.3% and tended to be lower than that in the 'incomplete cessation' group (13.7%) and 'no cessation' group (21.2%). Multivariate analysis revealed that 'no cessation' was a risk factor for DFS (hazard ratio [HR] = 4.25) and local recurrence rate (HR = 16.5, p < .05) compared to 'complete cessation.' DISCUSSION: We confirmed that the 'complete cessation' group had better prognosis than the 'no cessation' group by monitoring expiratory CO during radiation therapy for early stage glottic carcinoma. Moreover, monitoring expiratory CO was easier and more suitable than conventional methods for evaluating smoking cessation because it provided real-time measurements.

[Two Cases of Lung Stage â ¢Squamous Cell Carcinoma Treated with Carboplatin (CBDCA)plus Nab-Paclitaxel(Nab-PTX)].

Case 1: 83 years old man. For left upper lobe lungs squamous cell carcinoma infiltrating left main pulmonary artery. After 2 courses went of carboplatin(CBDCA)(AUC: 6)+weekly nab-paclitaxel(nab-PTX)(AUC: 6)+, left upper lobectomy and ND2 lymph nodes dissection. Tumor disappeared in pathology and diagnosed of Ef. 3. Case 2: 81 years old man. Right upper lobe lungs squamous cell carcinoma in #4R lymph node metastasis with the superior vena cava invasion. After 2 courses went of CBDCA(AUC: 6)+weekly nab-PTX(100mg/m2), left upper lobectomy and ND2 lymph nodes dissection. Tumor disappeared in pathology and diagnosed of Ef. 3. Nab-PTX may be considered a preoperative chemotherapeutic agent of choice for squamous cell carcinoma.

Photocontrol of cell adhesion on amino-bearing surfaces by reversible conjugation of poly(ethylene glycol) via a photocleavable linker.

Dynamic control of cell adhesion on substrates is a useful technology in tissue engineering and basic biology. This paper describes a method for the control of cell adhesion on amino-bearing surfaces by reversible conjugation of an anti-fouling polymer, poly(ethylene glycol) (PEG), via a newly developed photocleavable linker, 1-(5-methoxy-2-nitro-4-prop-2-ynyloxyphenyl)ethyl N-succinimidyl carbonate (1). This molecule has alkyne and succinimidyl carbonate at each end, which are connected by photocleavable 2-nitrobenzyl ester. Under this molecular design, the molecule crosslinked azides and amines, whose linkage cleaved upon application of near-UV light. By using aminosilanised glass and silicon as model substrates, we studied their reversible surface modification with PEG-azide (M(w) = 5000) based on contact angle measurements, ellipsometry, and AFM morphological observations. Protein adsorption and cell adhesion dramatically changed by PEGylation and the following irradiation, which can be used for cellular patterning. Also, the capability of the substrate to change cell adhesiveness by photoirradiation during cell cultivation was demonstrated by inducing cell migration. We believe this method will be useful for dynamic patterning of cells on protein-based scaffolds.

Silane coupling agent bearing a photoremovable succinimidyl carbonate for patterning amines on glass and silicon surfaces with controlled surface densities.

Patterned immobilization of synthetic and biological ligands on material surfaces with controlled surface densities is important for various bioanalytical and cell biological purposes. This paper describes the synthesis, characterization, and application of a novel silane coupling agent bearing a photoremovable succinimidyl carbonate, which enables the photopatterning of various primary amines on glass and silicon surfaces. The silane coupling agent is 1-[5-methoxy-2-nitro-4-(3-trimethoxysilylpropyloxy)phenyl]ethyl N-succinimidyl carbonate. The distinct feature of this molecule is that it has a photocleavable 2-nitrobenzyl switch between a trimethoxysilyl group and a succinimidyl carbonate, each reactive to the hydroxy groups of inorganic oxides and primary amines. Based on this molecular design, the compound allows for the one-step introduction of succinimidyl carbonates onto the surface of glass and silicon, immobilization of primary amines, and region-selective and dose-dependent release of the amines by near-UV irradiation. Therefore, we were able to pattern amine ligands on the substrates in given surface densities and arbitrary geometries by controlling the doses and regions of photoirradiation. These features were verified by UV-vis spectroscopy, contact angle measurements, infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), ellipsometry, and atomic force microscopy (AFM). The compound was applied to form a chemical density gradient of amino-biotin on a silicon substrate in a range of 0.87-0.12 chains/nm(2) by controlling photoirradiation under a standard fluorescence microscope. Furthermore, we also succeeded in forming a chemical density gradient at a lower surface density range (0.15-0.011 chains/nm(2)) on the substrate by diluting the feed amino-biotin with an inert control amine.