Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Peripheral blood immune cell-based biomarkers in anti-PD-1/PD-L1 therapy

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anti-cancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

Peripheral blood immune cell-based biomarkers in anti-PD-1/PD-L1 therapy

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anti-cancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

Peripheral blood immune cell-based biomarkers in anti-PD-1/PD-L1 therapy

Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anti-cancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

The History of Hospice and Palliative Care in Korea / 한국호스피스완화의료학회지

The first hospice care center in Korea dates back to the East West Infirmaries (Dongseodaebiwon in the Korean language) of the Goryeo period in the early 11th century. It has been 50 years since hospice care was introduced in Korea. Initially hospice care was provided in the private sector, including those with a religious background, and its development was slow. In the 1990s, related religious organizations and academic associations were established, and then, a full-swing growth phase was ushered in as the Korean government institutionalized hospice care in the early 2000s. As a result, enhanced quality of hospice care service could be provided, which meant better pain management and higher quality of life for late stage cancer patients and their families. Still, the nation lacked a realistic reimbursement system which was needed to for financial stability of the affected patients. However, the national health insurance scheme began to cover hospice palliative expenses in 2015. In 2016, the Act on Decisions on Life-Sustaining Treatment for Patients in Hospice and Palliative Care or at the End of Life was legislated, allowing terminally-ill patients to refuse meaningless life-sustaining treatments. As the range of diseases subject to hospice palliative care was expanded, more challenges and issues need to be addressed by the service providers.

Associations between Sleep Duration and Smoked Cigarettes per Day, Heavy Smoking in Smokers

BACKGROUND: This study was performed to evaluate the associations between sleep duration and smoked cigarettes per day, prevalence of heavy smoking. METHODS: This study was based on the data of 9,893 subjects who are currently smoking, from the 4th to 6th Korea National Health and Nutrition Examination Survey. Based on appropriate sleep duration from National Sleep Foundation, study subjects were categorized into short, appropriate and over sleep group. Multiple regression analysis was performed to evaluate the association between sleep duration and smoked cigarettes per day, prevalence of heavy smoking. Age, gender, household income, education, marital status, occupation, alcohol use, body weight, hypertension, diabetes mellitus, depression, and level of stress were controlled. RESULTS: Compared with appropriate sleep group, smoked cigarettes per day and prevalence of heavy smoking were higher in short sleep group, and lower in over sleep group. CONCLUSIONS: There is association between sleep duration and smoked cigarettes per day, prevalence of heavy smoking.

Associations between Sleep Duration and Smoked Cigarettes per Day, Heavy Smoking in Smokers

BACKGROUND@#This study was performed to evaluate the associations between sleep duration and smoked cigarettes per day, prevalence of heavy smoking.@*METHODS@#This study was based on the data of 9,893 subjects who are currently smoking, from the 4th to 6th Korea National Health and Nutrition Examination Survey. Based on appropriate sleep duration from National Sleep Foundation, study subjects were categorized into short, appropriate and over sleep group. Multiple regression analysis was performed to evaluate the association between sleep duration and smoked cigarettes per day, prevalence of heavy smoking. Age, gender, household income, education, marital status, occupation, alcohol use, body weight, hypertension, diabetes mellitus, depression, and level of stress were controlled.@*RESULTS@#Compared with appropriate sleep group, smoked cigarettes per day and prevalence of heavy smoking were higher in short sleep group, and lower in over sleep group.@*CONCLUSIONS@#There is association between sleep duration and smoked cigarettes per day, prevalence of heavy smoking.

Prognoses and Clinical Outcomes of Primary and Recurrent Uveal Melanoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood of recurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters. MATERIALS AND METHODS: Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival, and overall survival from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy. RESULTS: Forty-nine patients (21.7%) had distant recurrences, which occurred most frequently in the liver (87.7%). In a multivariate analysis, local radiotherapy improved RFS among patients with multiple recurrence risk factors relative to excision (not reached vs. 19.0 months, p=0.004). Patients with BRCA1-associated protein-1 (BAP1)–negative primary tumors showed a longer RFS duration after primary treatments, while those with BAP1-negative metastatic tissues had a shorter OS2 compared to those with BAP1-positive tumors, both not statistically insignificance (RFS: not reached vs. 82.0 months, p=0.258; OS2: 15.7 vs. 24.4 months, p=0.216). Male sex (hazard ratio [HR], 3.79; p=0.012), a short RFS (HR, 4.89; p=0.014), and a largest metastatic tumor linear diameter ≥ 45 mm (HR, 5.48; p=0.017) were found to correlate with worse post-recurrence survival. CONCLUSION: Risk factors could be used to classify uveal melanoma cases and subsequently direct individual treatment strategies. Furthermore, metastasectomy appears to contribute to improved survival outcomes.

Hospice & Palliative Care Policy in Korea / 한국호스피스완화의료학회지

Globally, efforts are being made to develop and strengthen a palliative care policy to support a comprehensive healthcare system. Korea has implemented a hospice and palliative care (HPC) policy as part of a cancer policy under the 10 year plan to conquer cancer and a comprehensive measure for national cancer management. A legal ground for the HPC policy was laid by the Cancer Control Act passed in 2003. Currently in the process is legislation of a law on the decision for life-sustaining treatment for HPC and terminally-ill patients. The relevant law has expanded the policy-affected disease group from terminal cancer to cancer, human immunodeficiency virus/acquired immune deficiency syndrome, chronic obstructive pulmonary disease and chronic liver disease/liver cirrhosis. Since 2015, the National Health Insurance (NHI) scheme reimburses for HPC with a combination of the daily fixed sum and the fee for service systems. By the provision type, the HPC is classified into hospitalization, consultation, and home-based treatment. Also in place is the system that designates, evaluates and supports facilities specializing in HPC, and such facilities are funded by the NHI fund and government subsidy. Also needed along with the legal system are consensus reached by people affected by the policy and more realistic fee levels for HPC. The public and private domains should also cooperate to set HPC standards, train professional caregivers, control quality and establish an evaluation system. A stable funding system should be prepared by utilizing the long-term care insurance fund and hospice care fund.

Incidence of Febrile Neutropenia in Korean Female Breast Cancer Patients Receiving Preoperative or Postoperative Doxorubicin/Cyclophosphamide Followed by Docetaxel Chemotherapy / 한국유방암학회지

PURPOSE: Doxorubicin/cyclophosphamide followed by docetaxel chemotherapy (AC-D) is an intermediate risk factor (incidence of 10%–20%) for febrile neutropenia (FN) in breast cancer. However, the reported incidence of FN while using this regimen was obtained mostly from Western breast cancer patients, with little data available from Asian patients. This study aimed to assess the incidence of FN in Korean breast cancer patients and to describe clinical variables related to FN. METHODS: From September 2010 to February 2013, data from the Yonsei Cancer Center registry of breast cancer patients who received neoadjuvant or adjuvant chemotherapy with four cycles of AC-D (60 mg/m2 doxorubicin, 600 mg/m2 cyclophosphamide every 3 weeks for four cycles followed by 75 mg/m2 or 100 mg/m2 docetaxel every 3 weeks for four cycles) were analyzed. The incidence of FN, FN associated complications, dose reduction/delays, and relative dose intensity (RDI) were investigated. RESULTS: Among the 254 patients reported to the registry, the FN incidence after AC-D chemotherapy was 29.5% (75/254), consisting of 25.2% (64/254) events during AC and 4.7% (12/254) during docetaxel chemotherapy. Dose reductions, delays, and RDI less than 85.0% during AC were observed in 16.5% (42/254), 19.5% (47/254), and 11.0% (28/254) of patients, respectively. Patients with FN events frequently experienced dose reduction/delays, which eventually led to a decreased RDI. CONCLUSION: The incidence of FN during AC-D neoadjuvant or adjuvant chemotherapy was higher than expected in Korean breast cancer patients. Whether these patients should be classified as a high-risk group for FN warrants future prospective studies.

Massive barium sulfate aspiration during upper gastrointestinal contrast material study in an elderly patient with dysphagia / 영남의대학술지

Barium sulfate is an inert material used as a radiographic contrast medium during upper gastrointestinal contrast studies for evaluation of patients with dysphagia. Oral barium aspiration is an uncommon but well-reported complication of this procedure. While barium aspiration of small amounts may not cause any symptoms, massive barium aspiration can be life-threatening, particularly in elderly patients with multiple comorbidities. In this case report, we describe an elderly patient with multiple comorbidities who presented with thyrotoxicosis and dysphagia, and then died after massive barium aspiration. Despite administration of intensive medical care with ventilator support and therapeutic bronchoalveolar lavage to remove the aspirated barium, the patient died of multiple organ failure 9 days after barium aspiration. Clinicians should pay attention to elderly patients with predisposing factors for aspiration in whom upper gastrointestinal barium contrast studies are indicated, and should consider other diagnostic tools for evaluation of dysphagia in this population.

Art Therapy and Hospice & Palliative Care in Korea / 한국호스피스완화의료학회지

In Korea, modern art therapy was developed in the 1960s and 1970s in the form of supplementary activities for patients in psychiatry. Along with the foundation of the Korean Association for Clinical Art in 1982 by psychiatric doctors, the therapy involved more various arts forms such as music, art, dance, poetry therapy, and psychodrama. More organizations with specific expertise opened such as the Korean Art Therapy Association, Korean Art Therapy Association, etc. in the 1990s and the Korea Arts Therapy Institute in 2001. As of April 2015, the members of the Korean Art Therapy Association total 15,000, including 6,200 regular members. The arts in integrative arts therapy (IAT) is an individual's creative activity which is related to his inner world, and the forms of IAT include music, drawing, dance and poetry therapy. From the aspect of phenomenology, IAT is psychophysical therapy involving the arts that helps patients recognize and perceive their experiences with an aim of at a recovery of the body and creativity from the phenomenological aspect. It is also a therapeutic activity that targets growth and development of the body and mind. Meta-analysis of the effects of art therapy with a focus on that involving music, drawing, dance movement and IAT in recent years in Korea, significant effects were observed in all factors but physical function. The biggest effect was mentality adaptation followed by activity adaptation and physiology. In the run up to the implementation of the daily flat-rate system for the health insurance reimbursement for palliative care in July 2015, the Ministry of Health and Welfare is reviewing the coverage of music therapy, drawing therapy and flower therapy, which are currently practiced by 56 hospice institutes in Korea. This is a meaningful step because the coverage of hospice and palliative care came after that of art therapy for psychiatric patients was approved in 1977. Still, there is a need clarify the therapeutic mechanism by exploring causality among the treatment media, mediation type and treatment effects. To address the issue of indiscriminately issued licenses, more efforts are needed to ensure expertise and identity of the licensed therapists through education, training and supervision.

Spirituality and Stress in Mental Health Social Workers / 한국호스피스완화의료학회지

PURPOSE: This study was conducted to analyze the association between spirituality and stress of mental health social workers, which could be used in development of a program to help them manage stress and offer spiritual support. METHODS: Participants were 154 mental health social workers in Korea. Data were collected from November 1 through November 30, 2011. The study employed the Korean version of the Spirituality Scale and Psychosocial Well-being Index-Short Form (PWI-SF). Data were analyzed using SPSS/Windows 17.0. RESULTS: The mean score for the Spirituality Scale was 3.63 and for PWI-SF 18.78. Spirituality scores showed a significant difference among participants by age, education, religion and marital status. Psychosocial stress scores also significantly differed by marital status. Spirituality scores were negatively correlated with psychosocial stress scores (r=-0.548, P<0.001). CONCLUSION: In this study, a significant negative association was found between spirituality and stress in mental health social workers in Korea. A follow-up study with a larger sample of participants is needed to confirm these findings.

Spirituality and State Hope of Medical Social Workers / 한국호스피스완화의료학회지

PURPOSE: This study was designed to assess the relationship between spirituality and state hope of medical social workers in Korea and their correlation was studied to provide data in developing effective spiritual and hope intervention for medial social workers. METHODS: The study surveyed 102 medical social workers in Korea from September 1, 2011 to September 30, 2011. The study employed the Korean version of the State Hope Scale (SHS) and Spirituality Scales (SS). For data analysis, descriptive statistics, t-test, ANOVA, Pearson's correlation and simple regression were performed using the SPSS WIN ver. 17.0. RESULTS: Spirituality scores showed a significant difference according to religion. The mean score of spirituality was 3.80/5.00 and the mean score of state hope was 6.36/8.00. Spirituality scoresand state hope scoresshowed a significant positive association (P<0.001). CONCLUSION: This study showed a significant positive association between medical social workers'spirituality and their state hope of. Future studies would be needed to further explorespirituality and state hope.

Breaking Bad News for Terminal Cancer Patients in Korea / 한국호스피스완화의료학회지

No abstract available.

A Development of Psychosocial Problems Assessment Scale for Patients with Mental Disorders / 신경정신의학

OBJECTIVES: There have been no consistent reliable and valid tool for examining the psychosocial problems for the patients with mental disorders in Korea. The purpose of the present study is to develop a scale that examine the psychosocial problems for the patients with mental disorders and to test its reliability and validity. METHODS: To identify the psychosocial problems for 1,100 patients with mental disorders were selected in university hospitals and professional training institutes. And the items of the psychosocial problems were taken from them and divided them into individual and environmental categories. The representative items were established among these items of psychosocial problems and a questionnaire for a pilot study was made based on the representative items. The pilot study was done for 306 patients with mental disorders using the questionnaire to investigate reliability of the questionnaire. After the pilot study items and format of the questionnaire were revised and complemented. The revised questionnaire was given to 600 patients with mental disorders to test its validity and reliability and new scale for psychosocial problems was developed. RESULTS: At the pilot study, which was performed with 1,100 patients, 3,200 items of psychosocial problems of 205 types were selected. Among these items 78 representative psychosocial problems items were withdrawn. Fifty-eight psychosocial problem items were finally set for the questionnaire after discussing them with the expert groups and examining its content reliability. Forty-seven psychosocial problems items were finally selected and given to 306 subjects at the pilot study. At the main study in which 600 subjects were tested inner-reliability. Correlation between items and scale was relevant and correlation coefficient between test and retest was high. The finally developed psychosocial problems testing scales were consisted of 46 testing items into 9 areas. CONCLUSION: The Psychosocial Problems Assessment Scale, which were developed at this study is proved to be valid and reliable and it will be able to be used to examine overall psychosocial problems for the patients with mental disorders in Korea.

Characteristics of hypoxia-induced ANP Secretion in Perfused Beating Atria / 대한흉부외과학회지

BACKGROUND: Cardiac atrium is an endocrine gland secreting a family of natriuretic peptides. The secretion of atrial natriuretic peptide(ANP) had been shown to be controlled by variable factors. The change in atrial dynamics have been considered as one of the most prominent stimuli for the stimulation of ANP secretion. Hypoxic stress has been shown to increase cardiac ANP secretion. However, the mechanism by which hypoxia increases ANP secretion cardiac ANP secretions. However, the mechanism by which hypoxia increases ANP secretion has not to be defined. Therefore, the purpose of the present study was tow-fold: to develop a protocol to defined the effect of hypoxia on ANP secretion in perfused beating rabbit atria and to clarify the mechanism responsible for the accentuation by hypoxia of ANP secretion. MATERIAL AND METHOD: Experiments have been done in perfused beating rabbit atria. ANP was measured by radioimmunoassay. RESULT: Hypoxic stimulus with nitrogen decreased atrial stroke volume. The decrease in atrial stroke volume recovered basal level during the period of recovery with oxygen. ANP secretion and the concentration of perfusate ANP in terms of extracellular fluid(ECF) translocation which reflects the rate of myocytic release of ANP were increased by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled by hypoxia and returned to basal levels during the recovery. Changes in ECF translocation paralleled to that of atrial stroke volume. At the start of recovery in atrial storke volume, ECF tranalocation incrased for several minutes. The above responses were stable and reproducible. Glibenclamide treatment prevented the recovery in atrial stroke volume. Increments by hypoxia of ANP secretion and ANP concentration were suppressed by glibenclamide. CONCLUSIONS: These results indicate that hypoxia incrased atrial myocytic ANP release and that the mechanism responsible for the accentuation is partially related to the change in K+ATP channel activity.

Clinical Study of Primary Chest Wall Tumors / 대한흉부외과학회지

Between January 1979 and August 1996, resection of a primary chest wall tumor was done in 51 patients. The mean age of the patients was 36.1 years (2 to 69 years). A palpable mass was the most common symptom (32 patients, 62.7%). The tumor was malignant in 11 patients (21.6%) and benign in 40 patients (78.4%). The tumors in 32 patients (62.7%) had developed from the bony or the cartilaginous wall and in 19 patients (37.3%) from soft tissue. Thirty seven of the patients with benign tumors were treated by excision (three of the patients: wide resection and reconstruction) without recurrence or death, and they are currently free from disease. Most malignancies (8 patients) were treated by wide resection and chest wall reconstruction. Five of them are currently alive. The chest wall reconstruction with Marlex mesh, Prolene mesh, or Teflon felt was done in five of the patients with malignant tumors.

Atypical Bronchopulmonary Carcinoid with Oncocytic Change: 1 Case Report / 대한흉부외과학회지

Atypical bronchopulmonary carcinoid is an uncommon pulmonary tumor, an intermediate form between low grade malignant typical carcinoid and high grade malignant small cell carcinoma which is considered neuroendocrine in origin and may produce various hormones. We describe an asymptomatic middle aged women with no elevated hormone level. Based on bronchoscopic biopsy initial diagnosis of atypical carcinoid with oncocytic change was established. The patient underwent right lower and middle lobe bilobectomy and mediastinal lymph node dissection. Postoperative adjuvant radiation therapy was performed in 4 weeks.

Long Term Results of Valve Replacement with the St. Jude Medical Heart Valves: Thirteen Year Experience / 대한흉부외과학회지

Between May 1984 and January 1996, 130 patients were replaced cardiac valve using 150 St. Jude Medical prosthetic valves(42 aortic, 68 mitral, 20 aortic and mitral valve replacements). Follow-up was 97.6% complete. The early mortality rate was 5.4%, and late mortality rate was 4.9%. The valve-related late mortality rate was 3.3%. Of late complications, there were 6 anticoagulant related hemorrhages, 4 thromboembolisms and 1 paravalvular leakage. Linearized rates of late complication and valve-related late mortality were as follows: total late complications, 1.68% per patient-year: anticoagulant related hemorrhages, 0.92% per patient-year: thromboembolism, 0.61% per patient-year: paravalvular leakage, 0.15% per patient-year: reoperation, 0.15% per patient-year: and valve-related late mortalities, 0.61% per patient-year. Actuarial event free rate at 10 years was 87.4+/-3.2%. The overall actuarial survival rate was 90.4+/-2.7% at 5 years, 87.5+/-3.3% at 10 years. Ninety eight percent of the survivors were in the New York Heart Association functional class I or II at the end of follow-up. There was significant improvement of cardiothoracic ratio. In conclusion, this study suggests the excellent durability of the St. Jude Medical Heart valve and remarkable functional benefit for the majority of the patients. However, prosthesis- related complications are still common. Outcome is strongly related to the patient's preoperative cardiac condition and to the adequacy of anticoagulation control.