Multimodal real-time imaging with laser speckle contrast and fluorescent contrast.

INTRODUCTION: Laser speckle contrast imaging (LSCI) can achieve real-time 2D perfusion maps non-invasively. However, LSCI is still difficult to use in general clinical applications because of movement sensitivity and limitations in blood flow analysis. To overcome this, fluorescence imaging (FI) is combined with LSCI using a light source with a wavelength of 785 nm in near-infrared (NIR) region and validates to visualize real-time blood perfusion. MATERIALS AND METHODS: The system was performed using Intralipid and indocyanine green (ICG) in a flow phantom that has three tubes and controlled the flow rate in 0-150 µl/min range. First, real-time LSCI was monitored and measured the change in speckle contrast by reperfusion. Then, we visualized blood perfusion of a rabbit ear under the non-invasive condition by intravenous injection using a total of five different ICG concentration solutions from 128 µM to 3.22 mM. RESULTS: The combined system achieved the performance of processing laser speckle images at about 37-38 fps, and we simultaneously confirmed the fluorescence of ICG and changes in speckle contrast due to intralipid as a light scatterer. In addition, we obtained real-time contrast variation and fluorescent images occurring in rabbit's blood perfusion. CONCLUSIONS: The aim of this study is to provide a real-time diagnostic imaging system that can be used in general clinical applications. LSCI and FI are combined complementary for observing tissue perfusion using a single NIR light source. The combined system could achieve real-time visualization of blood perfusion non-invasively.

Application of Polarization Sensitive-Optical Coherence Tomography to the Assessment of Phase Retardation in Subpleural Cancer in Rabbits.

BACKGROUND: Polarization sensitive-optical coherence tomography (PS-OCT) provides the unique advantage of being able to measure the optical characteristics of tissues by using polarized light. Although the well-organized fibers of healthy muscle can change the polarization states of passing light, damaged tissue has different behaviors. There are studies on optical imaging methods applied to the respiratory organs; however, they are restricted to structural imaging. In particular, the intercostal muscle situated under the pleura is very challenging to visualize due to the difficulty of access. METHOD: In this study, PS-OCT was used to identify subpleural cancer in male New Zealand white rabbits (3.2-3.4 kg) and to assess the phase retardation changes in normal and cancerous chest walls. VX2 cell suspension was injected between the intercostal muscle and parietal pleura and a tented area was observed by thoracic scope. A group of rabbits (n = 3) were sacrificed at day 7 after injection and another group (n = 3) at day 14. RESULTS: In the PS-OCT images, pleura thickness changes and muscle damage were criteria to understand the stages of the disease. The results of image and phase retardation analysis matched well with the pathologic examinations. CONCLUSION: We were able to visualize and analyze subpleural cancer by PS-OCT, which provided structural and functional information. The measured phase retardation could help to identify the margin of the tumor. For further studies, various approaches into other diseases using polarization light are expected to have positive results.

Investigation of the Clinical Potential of Polarization-Sensitive Optical Coherence Tomography in a Laryngeal Tumor Model.

BACKGROUND: The vocal cord tissue consists of three anatomical layers from the surface to deep inside: the epithelium that contains almost no collagen, the lamina propria that is composed of abundant collagen, and the vocalis muscle layer. It is clinically important to visualize the tissue microstructure using a non-invasive method, especially in the case of vocal cord nodules or cancer, since histological changes in each layer of the vocal cord cause changes in the voice. Polarization-sensitive optical coherence tomography (PS-OCT) enables phase retardation measurement to evaluate birefringence of tissue with varied organization of collagen fibers in different tissue layers. Therefore, PS-OCT can visualize structural changes between normal and abnormal vocal cord tissue. METHOD: A rabbit laryngeal tumor model with different stages of tumor progression was investigated ex-vivo by PS-OCT. A phase retardation slope-based analysis, which quantifies the birefringence in different layers, was conducted to distinguish the epithelium, lamina propria, and muscle layers. RESULTS: The PS-OCT images showed a gradual decrease in birefringence from normal tissue to advanced tumor tissue. The quantitative analysis provided a more detailed comparison among different stages of the rabbit laryngeal tumor model, which was validated by the corresponding histological findings. CONCLUSION: Differences in tissue birefringence was evaluated by PS-OCT phase retardation measurement. It is also possible to indirectly infer the dysplastic changes based on the mucosal and submucosal alterations.

Relationship between Cancer Stem Cell Marker CD133 and Cancer Germline Antigen Genes in NCI-H292 Lung Cancer Cells.

BACKGROUND: Previous studies have shown that lung cancer stem cells express CD133 and that certain cancer stem cells express cancer germline antigens (CGAs). The transcriptional regulation of CD133 is complicated and poorly understood. We investigated CD133 and CGA expression in a non-small cell lung cancer cell line. METHODS: The expression levels of CD133 and CGAs (MAGE-6, GAGE, SSX, and TRAG-3) were measured in an NCI-H292 lung cancer cell line. The methylation status of the CD133 gene promoter region was analyzed. The expression levels and promoter methylation statuses of CD133 and CGAs were confirmed by treatment with the demethylating agent 5-aza-2'-deoxycytidine (ADC). RESULTS: After treatment with ADC, CD133 expression was no longer detected. MAGE-6 and TRAG-3 were detected before ADC treatment, while GAGE and SSX were not detected. ADC treatment upregulated MAGE-6 and TRAG-3 expression, while GAGE expression was still undetected after treatment, and only weak SSX expression was observed. GAGE expression was not correlated with expression of CD133, while the levels of expression of MAGE-6, TRAG-3, and SSX were inversely correlated with CD133 expression. CONCLUSION: These results showed that CD133 expression can be regulated by methylation. Thus, the demethylation of the CD133 promoter may compromise the treatment of lung cancer by inactivating cancer stem cells and/or activating CGAs.

End-of-Life Care Practice in Dying Patients after Enforcement of Act on Decisions on Life-Sustaining Treatment For Patients in Hospice and Palliative Care or at the End of Life : A Single Center Experience.

Purpose: The Act on Hospice and Palliative Care and Decisions on Life-Sustaining Treatment for Patients at the End of Life came into force in February 2018 in Korea. This study reviews the practices of end-of-life care for patients who withdrew or withheld lifesustaining treatment at a tertiary care hospital, addresses the limitations of the law, and discusses necessary steps to promote patient-centered self-determination. Methods: We retrospectively analyzed the medical records of patients who died after agreeing to withhold lifesustaining treatment in 2018 at our university hospital. The cause of death, the intensity of end-of-life care, and other characteristics were reviewed and statistically analyzed. Results: Of a total of 334 patients, 231 (69%) died from cancer. The decision to stop life-sustaining treatment was made by family members for 178 patients overall (53.3%) and for 101 (43.7%) cancer patients, regardless of the patient's wishes. When the patient decided to stop lifesustaining treatment, the time from the authorization to withhold life-sustaining treatment to death was longer than when the decision was made by family members (28.7±41.3 vs 10.5±23.2 days, P<0.001). Conclusion: In many cases, the decision to discontinue lifesustaining treatment was made by the family, not by the patient. In order to protect human dignity based on the patients' self-determination, it is necessary for patients to understand their disease based on careful explanations from physicians. Ongoing survey-based research will be necessary in the future.

Unusual Communication between the Pulmonary Artery and Vieussens' Arterial Ring Causing Infective Endocarditis.

Coronary artery fistula is an abnormal communication between the coronary artery and the cardiac chambers. In particular, an abnormal connection between the conus branch of the right coronary artery and the proximal left anterior descending coronary artery is defined as Vieussens' arterial ring. Coronary artery fistulas are usually asymptomatic, but some can cause complications such as infective endocarditis. Here, we report a case of Vieussens' arterial ring causing infective endocarditis with severe mitral regurgitation.

The Clinical Implications of Death Domain-Associated Protein (DAXX) Expression.

BACKGROUND: Death domain-associated protein (DAXX), originally identified as a pro-apoptotic protein, is now understood to be either a pro-apoptotic or an anti-apoptotic factor with a chromatin remodeler, depending on the cell type and context. This study evaluated DAXX expression and its clinical implications in squamous cell carcinoma of the esophagus. METHODS: Paraffin-embedded tissues from 60 cases of esophageal squamous carcinoma were analyzed immunohistochemically. An immune reaction with more than 10% of tumor cells was interpreted as positive. Positive reactions were sorted into 2 groups: reactions in 11%-50% of tumor cells and reactions in more than 51% of tumor cells, and the correlations between expression and survival and clinical prognosticators were analyzed. RESULTS: Forty-three of the 60 cases (71.7%) showed strong nuclear DAXX expression, among which 19 cases showed a positive reaction (31.7%) in 11%-50% of tumor cells, and 24 cases (40.0%) showed a positive reaction in more than 51% of tumor cells. A negative reaction was found in 17 cases (28.3%). These patterns of immunostaining were significantly associated with the N stage (p=0.005) and American Joint Committee on Cancer stage (p=0.001), but overall survival showed no significant difference. There were no correlations of DAXX expression with age, gender, or T stage. However, in stage IIB (p=0.046) and stage IV (p=0.014) disease, DAXX expression was significantly correlated with survival. CONCLUSION: This investigation found upregulation of DAXX in esophageal cancer, with a 71.7% expression rate. DAXX immunostaining could be used in clinical practice to predict aggressive tumors with lymph node metastasis in advanced-stage disease, especially in stages IIB and IV.

Surgical Treatment of Primary Pulmonary Myopericytoma.

Myopericytoma is a benign tumor that occurs in soft tissues. Myopericytoma in the lungs is very rare. We report the case of a 63-year-old woman presenting with cavitary masses in the left lung and multiple tiny nodules in both lungs. She underwent surgery, and a histological examination revealed primary pulmonary myopericytoma.

Expression of the brother of the regulator of imprinted sites gene in the sputum of patients with lung cancer.

BACKGROUND: Brother of the regulator of imprinted sites (BORIS) is a putative new oncogene that is classified as a cancer germline gene; however, its role in the development of cancer is unclear. This study investigated the expression of BORIS in lung cancer and its clinical implications. METHODS: The expression of BORIS messenger ribonucleic acid (mRNA) in the sputum of 100 patients with lung cancer (50 with squamous cell carcinoma, 36 with adenocarcinoma, and 14 with small-cell carcinoma) was evaluated by reverse transcription polymerase chain reaction. RESULTS: The overall expression rate of BORIS in patients with lung cancer was 36.0%: 19 of 50 squamous cell carcinomas (38.0%), 13 of 36 adenocarcinomas (36.1%), and 4 of 14 (28.6%) small-cell carcinomas. There was no significant difference in the BORIS expression according to age, gender, or histologic type. However, the mRNA expression of BORIS was significantly related to the pathologic cancer stage (p=0.004) and lymph node metastasis (p=0.001). The expression of the melanoma antigen gene family A1-6 was not associated with the expression of BORIS. CONCLUSION: Our results suggest that the expression of BORIS might be a negative prognostic factor in lung cancers and implicate BORIS as a molecular target for immunotherapy.

Saccular aneurysm of the external jugular vein: a case report.

Saccular aneurysm of the external jugular vein presenting as a neck mass is very rare. We report the surgical treatment of an external jugular venous aneurysm in a 48-year-old female patient due to the cosmetic problem of neck engorgement, concomitant with thyroidectomy for cancer.

Primary epithelial myoepithelial lung carcinoma.

Primary epithelial-myoepithelial carcinoma (EMC) of the lung is an extremely rare neoplasm that originates from submucosal bronchial glands and has been found in the salivary glands, breast tissue, and sweat glands. However, only a few cases in the respiratory tract have been identified. In the literature, most pulmonary EMCs have been reported to have developed endobronchially although a few EMC cases have been presented as intraparenchymatous tumors. We have identified a case of primary EMC that developed in the peripheral lung parenchyma.