Effect of a combination of Korean red ginseng extract and probiotics on the prevention of atopic dermatitis in a murine model.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C.A.Mey. (Korea red ginseng) has been used in Asia to treat inflammatory skin diseases. Recently, Korea red ginseng (KRG) is emerging as a good candidate for treating atopic dermatitis (AD) because of its anti-allergic and anti-inflammatory effects. AIM OF THE STUDY: Despite much effort, no systemic prevention strategy has been established for AD currently. Therefore, the aim of this study was to determine the preventive effect of a combination of KRG extract and probiotics on AD-like skin lesions of mice. MATERIALS AND METHODS: Forty NC/Nga mice were randomly divided into eight groups: Sham, AD control, Cyclosporine, KRG, Duolac ATP® (ATP), BYO Plant Origin Skin Probiotics (BYO), KRG + ATP, and KRG + BYO. Mice were administered orally with KRG and/or other agents using a gastric tube for 5 days prior to challenge with 1-chloro-2,4-dinitrobenzene (DNCB). AD-like skin lesions were induced by percutaneous challenge with DNCB on ears and backs of NC/Nga mice. Effects of each treatment were evaluated based on the following: Clinical severity score, ear thickness, transepidermal water loss (TEWL), total serum Immunoglobulin E (IgE) level, mRNA expression levels and immunohistochemistry analysis of IFN-γ, IL-4, and TSLP in cutaneous lesions. RESULTS: TEWL, serum IgE level, and expression of immunohistopathologic markers were more improved in the group using KRG combined with probiotics than in the group using KRG or probiotics alone. ATP, KRG + ATP, and KRG + BYO groups showed reduced TEWL increase (ΔTEWL) at 48 h (p < 0.005). KRG + ATP showed a preventive effect on the increase of serum IgE level (p = 0.009). In immunohistopathologic analysis, KRG, ATP, BYO, KRG + ATP, and KRG + BYO groups showed significantly reduced expression levels of IFN-γ at 1 h, 6 h, and 48 h (all p < 0.05). KRG, ATP, BYO, and KRG + BYO groups showed reduced expression levels of IL-4 compared to the AD control group at 6 h and 24 h. KRG, ATP, BYO, KRG + ATP, and KRG + BYP groups showed significantly lower expression levels of TSLP than the AD control group at 1 h and 24 h. CONCLUSION: KRG can suppress increases of allergic and inflammatory cytokines and increase of TEWL. A combination of KRG and probiotics might have better effects than KRG or probiotics alone for preventing an AD flare-up.

Systemic Comorbidities in Korean Patients with Rosacea: Results from a Multi-Institutional Case-Control Study.

Recent evidence links rosacea to systemic disease, but there are not enough methodologic studies addressing this association in Asians. Our aim was to identify rosacea comorbidities in Koreans and establish a reference database. A multi-center, case-control study was performed where a total of 12,936 rosacea patients and 12,936 age- and sex-matched control subjects were identified from 2007 to 2018. Logistic regression was performed to find significant association between rosacea and Sjögren syndrome (odds ratio [OR] 2.05; 95% confidence interval, 1.40-3.00), systemic sclerosis (OR 6.56; 95% CI, 1.50-28.7), rheumatoid arthritis (OR 1.72; 95% CI, 1.50-1.98), ankylosing spondylitis (OR 2.32; 95% CI, 1.42-3.84), autoimmune thyroiditis (OR 1.96; 95% CI, 1.40-2.73), alopecia areata (OR 1.77; 95% CI, 1.27-2.45), vitiligo (OR 1.90; 95% CI, 1.30-2.77), lung cancer (OR 1.54; 95% CI, 1.06-2.21), hepatobiliary cancer (OR 1.38; 95% CI, 1.06-1.77), alcohol abuse (OR 1.59; 95% CI, 1.05-2.39), diabetes mellitus (OR 1.11; 95% 1.02-1.19), obesity (OR 1.72; 95% CI, 1.22-2.41), allergic rhinitis (OR 1.65; 95% CI, 1.54-1.76), allergic conjunctivitis (OR 1.57; 95% CI, 1.27-1.94), chronic rhinosinusitis (OR 1.28; 95% CI, 1.14-1.42), herpes infection (OR 1.69; 95% CI, 1.53-1.86), and human papillomavirus infection (OR 2.50; 95% CI, 2.06-3.02). Higher odds for Sjogren syndrome, systemic sclerosis, ankylosing spondylitis, thyroiditis, vitiligo, hepatobiliary cancer, and obesity was exclusive in female subjects with rosacea, whereas increased prevalence of alopecia areata and alcohol abuse was confined to men. Only those who were 50 years and older exhibited higher odds for vitiligo, lung cancer, and gastroesophageal reflux disease while individuals younger than 50 were exclusively associated with hepatobiliary cancer, allergic conjunctivitis, and irritable bowel syndrome. Our study suggests that Koreans with rosacea are more likely to experience systemic comorbidity. Clinicians should acknowledge these interrelations and employ comprehensive care with an individual-based approach.

Induction chemotherapy in head and neck squamous cell carcinoma of the paranasal sinus and nasal cavity: a role in organ preservation.

BACKGROUND/AIMS: The role of induction chemotherapy (IC) for eyeball preservation has not been established in head and neck squamous cell carcinoma (HNSCC) of the paranasal sinus and nasal cavity (PNSNC). Periorbital involvement frequently leads to eyeball exenteration with a margin of safety. We evaluated the treatment outcomes, including survival and eyeball preservation, of patients who received IC for HNSCC of the PNSNC. METHODS: We reviewed 21 patients diagnosed with HNSCC of the PNSNC who were treated with IC. We analyzed response, eyeball preservation rate, and overall survival. RESULTS: Tumors were located in the paranasal sinus (n = 14) or nasal cavity (n = 7). Most patients had stage T4a (n = 10) or T4b (n = 7) disease. More than half of the patients received a chemotherapy regimen of docetaxel, fluorouracil, and cisplatin (n = 11). Thirteen patients (61.9%) achieved a partial response after IC and 15 patients (71.4%) achieved T down-staging. Among 17 patients with stage T4 disease, which confers a high risk of orbital exenteration, 14 (82.4%) achieved preservation of the involved eye. The 3-year overall survival (OS) rate of patients who achieved a partial response to IC was 84.6%. The 3-year OS rate of patients with stable disease or disease progression after IC was 25.0% (p = 0.038). CONCLUSIONS: IC could be considered for down-staging patients with advanced T-stage disease. It could also be a reasonable option for eyeball preservation in locally advanced HNSCC of the PNSNC.

Nutritional status in the era of target therapy: poor nutrition is a prognostic factor in non-small cell lung cancer with activating epidermal growth factor receptor mutations.

BACKGROUND/AIMS: Pretreatment nutritional status is an important prognostic factor in patients treated with conventional cytotoxic chemotherapy. In the era of target therapies, its value is overlooked and has not been investigated. The aim of our study is to evaluate the value of nutritional status in targeted therapy. METHODS: A total of 2012 patients with non-small cell lung cancer (NSCLC) were reviewed and 630 patients with activating epidermal growth factor receptor (EGFR) mutation treated with EGFR tyrosine kinase inhibitor (TKI) were enrolled for the final analysis. Anemia, body mass index (BMI), and prognostic nutritional index (PNI) were considered as nutritional factors. Hazard ratio (HR), progression-free survival (PFS) and overall survival (OS) for each group were calculated by Cox proportional analysis. In addition, scores were applied for each category and the sum of scores was used for survival analysis. RESULTS: In univariable analysis, anemia (HR, 1.29; p = 0.015), BMI lower than 18.5 (HR, 1.98; p = 0.002), and PNI lower than 45 (HR, 1.57; p < 0.001) were poor prognostic factors for PFS. Among them, BMI and PNI were independent in multi-variable analysis. All of these were also significant prognostic values for OS. The higher the sum of scores, the poorer PFS and OS were observed. CONCLUSIONS: Pretreatment nutritional status is a prognostic marker in NSCLC patients treated with EGFR TKI. Hence, baseline nutritional status should be more carefully evaluated and adequate nutrition should be supplied to these patients.

Changes of Clinicopathologic Characteristics and Survival Outcomes of Anaplastic and Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: This study aimed to analyze the temporal changes of the clinicopathologic characteristics, and the long-term outcomes, of various types of anaplastic thyroid cancer (ATC) and poorly differentiated thyroid cancer (PDTC). METHODS: A retrospective analysis was conducted on patients with ATC and PDTC who were treated from 1985 to 2013. The outcome measures included the clinical response to treatment and the survival rates of three separate thyroid cancer groups: ATC, PDTC, and differentiated thyroid cancer (DTC) with anaplastic foci. RESULTS: The five-year disease-specific survival rate was significantly higher, both in DTC with anaplastic foci and in PTDC (81.3% and 65.8%, respectively), than it was in ATC (14.3%; p < 0.001). The proportion of cases of DTC with anaplastic foci has been increasing over time, while that of ATC has decreased. The survival rate was found to be significantly higher in resectable tumors (71.4% and 26.5%, respectively; p < 0 .001). In ATC, external beam radiation therapy showed longer survival rates than did surgery-based treatment in unresectable tumors (19.2 vs. 7.7 months, p = 0.006). Adjuvant treatment with external beam radiation or radioactive iodine increased survival duration in PDTC and in DTC with anaplastic foci. Lymphatic invasion was the most significant postoperative prognosticator in ATC (p = 0.013). CONCLUSIONS: The choice of treatment of ATC and PDTC could be modified according to resectability and lymphatic invasion of the cancer.

Comparative effects of artemisia vulgaris and charcoal moxa stimulating Zhongwan (CV 12) on body temperature in healthy participants: a cross-over single-blind randomized study.

OBJECTIVE: To evaluate the efficacy, safety, satisfaction, discomfort and patient preference of moxa cones of artemisia vulgaris and charcoal moxa. METHODS: This comparative study of moxibustion treatment with Artemisia vulgaris and charcoal moxa cone stimulating Zhongwan (CV 12) is a cross-over single-blinded, randomized clinical trial. A total of 40 healthy subjects (24 males and 16 females) participated in this study. Two subjects dropped out of the trial. Thirty-eight subjects were treated with Artemisia vulgaris and charcoal moxa cones for 30 min in a cross-over design. After treatment, the patients underwent a 30 minute waiting period, and then the temperatures at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4) were measured using digital infrared thermal imaging. RESULTS: After the use of Artemisia vulgaris moxa, the patients' body temperatures were slightly lowered at Tanzhong (CV 17), Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After the use of charcoal moxa, the patients' body temperatures were somewhat increased at Zhongwan (CV 12) and Guanyuan (CV 4), but the changes were not statistically significant. After Artemisia vulgaris moxa use, the body temperature difference between Zhongwan (CV 12) and Guanyuan (CV 4) was significantly increased. After charcoal moxa use, the body temperature difference between Tanzhong (CV 17) and Zhongwan (CV 12) was significantly decreased in males and in the whole group. This change was caused by the difference in the moxibustion type and by gender differences. CONCLUSION: This pilot study found that moxibustion did not raise the body temperature, but temperature differences between acupoints were affected. Further large-scale randomized controlled trials are needed for the effect of moxibustion on body temperature.

Multiplexed gene expression and fusion transcript analysis to detect ALK fusions in lung cancer.

Anaplastic lymphoma kinase gene (ALK) fusions have been identified in approximately 5% of non-small-cell lung carcinomas (NSCLCs) and define a distinct subpopulation of patients with lung cancer who are highly responsive to ALK kinase inhibitors, such as crizotinib. Because of this profound therapeutic implication, the latest National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology recommend upfront ALK screening for all patients with NSCLC. The Food and Drug Administration-approved companion diagnostic test (ie, fluorescence in situ hybridization) for identification of ALK-positive patients, however, is complex and has considerable limitations in terms of cost and throughput, making it difficult to screen many patients. To explore alternative screening modalities for detecting ALK fusions, we designed a combination of two transcript-based assays to detect for presence or absence of ALK fusions using NanoString's nCounter technology. By using this combined gene expression and ALK fusion detection strategy, we developed a multiplexed assay with a quantitative scoring modality that is highly sensitive, reproducible, and capable of detecting low-abundant ALK fusion transcripts, even in samples with a low tumor cell content. In 66 archival NSCLC samples, our results were highly concordant to prior results obtained by fluorescence in situ hybridization and IHC. Our assay offers a cost-effective, easy-to-perform, high-throughput, and FFPE-compatible screening alternative for detection of ALK fusions.

The factors associated with the quality of life of the spouse caregivers of patients with cancer: a cross-sectional study.

BACKGROUND: It is well known that cancer greatly affects not only patients but also their families. However, few studies on caregivers' quality of life have been conducted within the Asian population. METHODS: We carried out a survey using well-constructed, self-administered questionnaires that were answered by pairs of patients with cancer and their spouse-caregivers (n=100 pairs) who were visiting the cancer daycare center at Seoul National University Hospital. The caregiver's quality of life (QOL) was assessed by the Korean version of the Caregiver Quality Of Life Index-Cancer (CQOLC), which contains four domains along with other items. Possible determinants of caregiver QOL were categorized according to sociodemographic factors, caregiver burden, health risk factors, spirituality, and family function. Multiple linear regression analysis was used to identify the factors associated with spouse-caregivers' QOL. RESULTS: Having a reason or purpose for living was associated with the total CQOLC score (ß=3.408, p=0.025) and positive adaptation (ß=1.035, p=0.009). Family function was associated with total CQOLC and all the domains except burden, and caregivers' religion was associated with total CQOLC. Monthly household income and cigarette smoking status were associated with financial concern. CONCLUSIONS: Having a reason and purpose for living, which is an aspect of spirituality, was a relevant factor in the spousal caregivers' QOL. Future research is needed to confirm the association between spirituality and caregivers' QOL and whether interventions supporting spirituality could improve their QOL.

Discovery of novel inhibitors for human intestinal maltase: virtual screening in a WISDOM environment and in vitro evaluation.

Human intestinal maltase (HMA) is an α-glucosidase that hydrolyses α-1,4-linkages from the non-reducing end of malto-oligosaccharides. HMA is an important target to discover of new drugs for the treatment of type 2 diabetes. In this study, 308,307 compounds were virtually screened with HMA using Autodock 3.0.5 in a WISDOM production environment to discover novel inhibitors. The 42 top-scoring free binding energy compounds, representing 17 groups containing potential hydrogen bonding with key residues in the active site pocket of HMA, were tested in vitro for their inhibitory activities against recombinant HMA expressed from Pichia pastoris. Compounds 17 and 18 were competitive inhibitors exclusively for HMA without any in vitro inhibition for human pancreatic α-amylase. The K(i) values were 20 µM for both compound 17 and 18.

Increasing nodal ratio is a poor prognostic factor for survival in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant chemotherapy: a retrospective study.

OBJECTIVE: The aim of this study is to evaluate the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin in gastric cancer patients and to assess prognostic factors affecting relapse and survival. METHODS: We retrospectively reviewed the data of 153 patients with Stage III-IV (M0) gastric cancer. The patients were given adjuvant 5-fluorouracil/cisplatin chemotherapy after curative gastric resection with D2 dissection from November 1995 to November 2003. Chemotherapy consisted of cisplatin (60 mg/m(2) as 15 min i.v. infusion) and 5-fluorouracil (1200 mg/m(2) as 12 h continuous i.v. infusion for 4 days) in every 21 days up to six cycles. RESULTS: During a median follow-up period of 72.9 months (range: 2.0-135.0 months), a total of 105 patients relapsed (locoregional 19.0% vs. systemic 81.0%). The median disease-free survival and overall survival were 19.8 and 32.2 months, respectively. Univariate analysis revealed T stage, TNM stage and lymph node ratio as prognostic factors for survival (P = 0.002, <0.0001 and <0.0001, respectively). After stepwise selection of the factors, multivariate analysis confirmed the impact of the lymph node ratio and T stage on overall survival and disease-free survival. CONCLUSIONS: In patients with Stage III-IV (M0) gastric cancer, adjuvant 5-fluorouracil/cisplatin chemotherapy was tolerable, but did not seem to confer survival advantage. And the lymph node ratio was found as an independent prognostic factor in this population. This evidence suggests that the clinical trial using more active chemotherapeutic agents is mandatory.

Patterns of palliative procedures and clinical outcomes in patients with advanced non-small cell lung cancer.

BACKGROUND: Despite recent progress in palliative chemotherapy for advanced non-small cell lung cancer (NSCLC), the prognosis is still poor. Aside from multiple lines of chemotherapy, many patients need palliative procedures due to disease-related events. The patterns of events requiring palliative procedures and their impact on the clinical course have not been well described. METHODS: We evaluated 162 patients who were diagnosed with stage IIIB (with malignant effusion) or IV NSCLC at Seoul National University Hospital in 2005. The patterns of disease-related events requiring palliative procedures, the palliative procedures given, and the clinical outcomes were retrospectively analyzed. RESULTS: Of the 162 patients, 107 were male (66%) and 55 were female (34%) with a median age of 61 years (range 31-90). Among these patients, 108 patients (66%) received palliative procedures due to disease-related events. Forty-nine patients (30%) needed a palliative procedure at the time of diagnosis, and 59 patients (36%) required palliative procedure later during the course of their treatment. The events requiring palliative procedures were thoracic events (malignant effusion or severe pneumonia requiring intensive care unit care not related to treatment) in 32 (30%), CNS events (brain metastasis or leptomeningeal metastasis) in 37 (34%), skeletal events (bone metastasis requiring radiation, spinal cord compression, hypercalcemia) in 29 (27%), and other events in 10 (9%). The patients who had events at the time of diagnosis showed comparable overall survival to the patients without events at the time of diagnosis (14.6 months vs. 13.3 months, p=0.65). The patients with later events during their course of treatment had a short median survival after the event requiring palliative procedures (median 2.7 months, 95% CI 2.19-3.21). CONCLUSION: A considerable proportion of patients with advanced NSCLC receive palliative procedures apart from chemotherapy. These interventions should be taken into consideration for comprehensive cancer care and timely cooperation with palliative care team.

Long-term survival of resectable subset after induction chemotherapy in patients with locally advanced head and neck cancer.

BACKGROUND: Although meta-analysis showed that survival improved with concurrent chemoradiation in locally advanced head and neck cancer, neoadjuvant chemotherapy is still unique, because it renders curative surgery feasible for marginally resectable head and neck cancer patients. METHODS: We reviewed patients with locally advanced head and neck cancer, who had been treated with neoadjuvant chemotherapy between June 1984 and February 2001 at the Seoul National University Hospital. RESULTS: A total of 167 patients were included. After 2 to 3 chemotherapy cycles, either surgery (38 patients) or radiation (104 patients) was conducted. Those who received surgery exhibited better survival than those who received radiation [median survival: not reached vs 33.6 months (95% CI: 22.6-44.7), p = .006]. The 5-year and 10-year survival rates of surgery group were 63.2% and 59.8%. CONCLUSION: The potential benefit of neoadjuvant chemotherapy with surgery in patients with locally advanced head and neck cancers merits further evaluation in future clinical trials.

An observational study suggesting clinical benefit for adjuvant postoperative chemoradiation in a population of over 500 cases after gastric resection with D2 nodal dissection for adenocarcinoma of the stomach.

PURPOSE: The role of adjuvant chemoradiotherapy (CRT) in D2-resected gastric-cancer patients has not been defined yet. We investigated the effect of postoperative chemoradiotherapy on the relapse rate and survival rate of patients with D2-resected gastric cancer. METHODS AND MATERIALS: From August 1995 to April 2001, 544 patients received postoperative CRT after curative D2 resection. During the same period of time, 446 patients received surgery without further adjuvant treatment. The adjuvant CRT consisted of 400 mg/m2 of fluorouracil plus 20 mg/m2 of leucovorin for 5 days, followed by 4,500 cGy of radiotherapy for 5 weeks, with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of radiotherapy. RESULTS: The median duration of overall survival was significantly longer in the CRT group than in the comparison group (95.3 months vs. 62.6 months), which corresponds to a hazard ratio for death of 0.80 (p = 0.0200) or a reduction of 20% in the risk of death in the CRT group. The 5-year survival rates were consistently longer in the CRT group at Stages II, IIIA, IIIB, and IV than those in the comparison group. The CRT was associated with increases in the median duration of relapse-free survival (75.6 months vs. 52.7 months; hazard ratio for relapse, 0.80, p = 0.0160). CONCLUSION: Our results highly suggest that the postoperative chemoradiotherapy in D2-resected gastric-cancer patients can prolong survival and decrease recurrence.