Lactobacillus acidophilus KBL409 Ameliorates Atopic Dermatitis in a Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with repeated exacerbations of eczema and pruritus. Probiotics can prevent or treat AD appropriately via modulation of immune responses and gut microbiota. In this study, we evaluated effects of Lactobacillus acidophilus (L. acidophilus) KBL409 using a house dust mite (Dermatophagoides farinae)-induced in vivo AD model. Oral administration of L. acidophilus KBL409 significantly reduced dermatitis scores and decreased infiltration of immune cells in skin tissues. L. acidophilus KBL409 reduced in serum immunoglobulin E and mRNA levels of T helper (Th)1 (Interferon-γ), Th2 (Interleukin [IL]-4, IL-5, IL-13, and IL-31), and Th17 (IL-17A) cytokines in skin tissues. The anti-inflammatory cytokine IL-10 was increased and Foxp3 expression was up-regulated in AD-induced mice with L. acidophilus KBL409. Furthermore, L. acidophilus KBL409 significantly modulated gut microbiota and concentrations of short-chain fatty acids and amino acids, which could explain its effects on AD. Our results suggest that L. acidophilus KBL409 is the potential probiotic for AD treatment by modulating of immune responses and gut microbiota of host.

Lactobacillus rhamnosus KBL2290 Ameliorates Gut Inflammation in a Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Ulcerative colitis, a major form of inflammatory bowel disease (IBD) associated with chronic colonic inflammation, may be induced via overreactive innate and adaptive immune responses. Restoration of gut microbiota abundance and diversity is important to control the pathogenesis. Lactobacillus spp., well-known probiotics, ameliorate IBD symptoms via various mechanisms, including modulation of cytokine production, restoration of gut tight junction activity and normal mucosal thickness, and alterations in the gut microbiota. Here, we studied the effects of oral administration of Lactobacillus rhamnosus (L. rhamnosus) KBL2290 from the feces of a healthy Korean individual to mice with DSS-induced colitis. Compared to the dextran sulfate sodium (DSS) + phosphate-buffered saline control group, the DSS + L. rhamnosus KBL2290 group evidenced significant improvements in colitis symptoms, including restoration of body weight and colon length, and decreases in the disease activity and histological scores, particularly reduced levels of pro-inflammatory cytokines and an elevated level of anti-inflammatory interleukin-10. Lactobacillus rhamnosus KBL2290 modulated the levels of mRNAs encoding chemokines and markers of inflammation; increased regulatory T cell numbers; and restored tight junction activity in the mouse colon. The relative abundances of genera Akkermansia, Lactococcus, Bilophila, and Prevotella increased significantly, as did the levels of butyrate and propionate (the major short-chain fatty acids). Therefore, oral L. rhamnosus KBL2290 may be a useful novel probiotic.

Nomogram Incorporating CD44v6 and Clinicopathological Factors to Predict Lymph Node Metastasis for Early Gastric Cancer.

BACKGROUND: Treatment strategy for early gastric cancer depends on the probability of lymph node metastasis. The aim of this study is to develop a nomogram predicting lymph node metastasis in early gastric cancer using clinicopathological factors and biomarkers. METHODS: A literature review was performed to identify biomarkers related to lymph node metastasis in gastric cancer. Seven markers were selected and immunohistochemistry was performed in 336 early gastric cancer tissues. Based on the multivariable analysis, a prediction model including clinicopatholgical factors and biomarkers was developed, and benefit of adding biomarkers was evaluated using the area under the receiver operating curve and net reclassification improvement. Functional study in gastric cancer cell line was performed to evaluate mechanism of biomarker. RESULTS: Of the seven biomarkers studied, α1 catenin and CD44v6 were significantly associated with lymph node metastasis. A conventional prediction model, including tumor size, histological type, lymphatic blood vessel invasion, and depth of invasion, was developed. Then, a new prediction model including both clinicopathological factors and CD44v6 was developed. Net reclassification improvement analysis revealed a significant improvement of predictive performance by the addition of CD44v6, and a similar result was shown in the internal validation using bootstrapping. Prediction nomograms were then constructed based on these models. In the functional study, CD44v6 was revealed to affect cell proliferation, migration and invasion. CONCLUSIONS: Overexpression of CD44v6 was a significant predictor of lymph node metastasis in early gastric cancer. The prediction nomograms incorporating CD44v6 can be useful to determine treatment plans in patients with early gastric cancer.

Biopathologic features and clinical significance of micrometatasis in the lymph node of early gastric cancer.

AIM: To evaluate the biopathologic features and clinical significance of nodal micrometastasis (MI) in early gastric cancer (EGC). METHODS: Among 1022 EGC patients who underwent gastrectomy with lymphadenectomy of D1 + ß or more from March 2001 to December 2005 at the Korean National Cancer Center, available nodal metastasis was found in 90 pT1N1 patients. Nodal metastasis was confirmed by immunohistochemistry (IHC) with cytokeratin and patients were classified into MI and macrometastasis (MA) groups based on the main tumor burden according to the 6(th) International Union Against Cancer/American Joint Committee on Cancer staging system; the main tumor burden with a diameter of greater than 0.2 mm but no greater than 2 mm as MI, and greater than 2 mm as MA of the representative metastatic node. Proliferative and apoptotic activities of the primary tumor and the nodal metastasis were measured by IHC with Ki-67 and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Biopathologic and clinical features of the patients were analyzed and compared between MI and MA groups. Patients with recurrence were compared with those without recurrence to identify risk factors for recurrence. RESULTS: Thirty-seven patients showed MI and the other 53 patients revealed MA in the lymph node; the incidence of patients with MI and MA was 41.1% and 58.9%. The main tumor burden was 0.9 and 4.6 mm in the representative metastatic node, respectively. Japanese N2 stations were more frequently involved in MA group (20.9%) than in MI group (10.3%) but the difference was not statistically different (P = 0.338). Proliferative and apoptotic activities of MI were decreased than those of MA (26.7% vs 40.5%, P = 0.004 and 1.0% vs 3.0%, P < 0.001, respectively). However, nodal MI in the current study showed a relatively high proliferative activity and an equivalent apoptotic activity compared to other cancers in the previously published studies. Recurrence was observed in 6 patients during the mean follow up period of 87.6 ± 26.2 mo. The recurrence was significantly associated with the presence of MA (P = 0.041) and lymphovascular invasion of the primary tumor (P = 0.032). CONCLUSION: Lymphadenectomy of D1 + ß or more might be necessary in patients with MI in sentinel node to prevent recurrence by clearing MI involving Japanese N2 station.

Health-related quality of life after robot-assisted distal gastrectomy in early gastric cancer.

PURPOSE: This study was designed to assess the chronological change in health-related quality of life (HRQOL) following robot-assisted distal gastrectomy (RADG) for early gastric cancer (EGC) and to compare the HRQOL of the patients undergoing RADG with that of the general population. METHODS: Patients undergoing RADG for EGC between March 2010 and May 2011 were enrolled. The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ-C30) and the gastric cancer-specific module (QLQ-STO22) were completed before the operation and at 1 week as well as 1, 3, 6, and 12 months postsurgery. HRQOL data of the enrolled patients were compared to reference values obtained from the general population. RESULTS: A total of 30 patients were enrolled, and the overall compliance for questionnaire response was 94.4 %. The worst scores for most of the domains were observed at 1 week postsurgery and usually returned to baseline levels within 3 months, except for fatigue, dysphagia, pain, and eating restriction. Diarrhea was the only symptom that did not recovered after 1 year. Before surgery, patients reported significantly worse social function and financial difficulties compared to the general population, which persisted for 1 year postsurgery. CONCLUSIONS: The immediate deterioration of HRQOL after RADG was restored to baseline levels within 3 months postsurgery in the majority of the patients. Robotic assistance might aid in the rapid recovery of global health status after surgery in EGC patients. Prolonged impairment in social function compared with the general population suggests that psychological support is necessary even for EGC patients.

The lymphangiogenic factor SOX 18: a key indicator to stage gastric tumor progression.

SOX group F genes are important regulators of angiogenesis and lymphangiogenesis. The aim of the present study was to examine the relationships between Sox group F expression and clinicopathological factors in gastric cancer. Three hundred and fifteen gastric cancer tissues and the corresponding normal gastric tissue were obtained from the tumor bank at the National Cancer Center, Korea. SOX group F mRNA levels in these tissues were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The serum levels of SOX 18 proteins in 219 gastric cancer patients and in 30 healthy volunteers were also measured by enzyme-linked immunosorbent assay. Furthermore, immunohistochemistry (IHC) was performed on 679 gastric cancer tissues and the clinicopathological characteristics, as well as the survival rates of SOX 18 positive and negative gastric cancers were compared. RT-PCR showed that SOX group F mRNA was increased in the gastric cancer tissues compared to the normal gastric tissues (p < 0.001, respectively). The serum levels of SOX 18 protein were also increased in gastric cancer patients compared to healthy volunteers. IHC showed that of the 679 gastric cancer cases, 177 (26.1%) were positive for SOX 18 expression in their tumor stroma, and the frequencies of both lymphovascular invasion and lymph node metastases were higher in the SOX 18 positive than in the negative group. Both the 5-year survival and the recurrence-free survival were shorter for SOX 18 positive tumors (p = 0.023 and 0.012, respectively). SOX 18 expression might be a prognostic tumor marker and a potential therapeutic target in gastric cancer.

Multidetector CT evaluation of total anomalous pulmonary venous connections: comparison with echocardiography.

BACKGROUND: Although echocardiography is the first-line imaging modality in the diagnosis of total anomalous pulmonary venous connection (TAPVC), multidetector CT (MDCT) could have advantages in the diagnosis of TAPVC in certain cases. OBJECTIVE: To compare MDCT with echocardiography in the evaluation of TAPVC. MATERIALS AND METHODS: Enrolled in the study were 23 patients with surgically proven TAPVC. The echocardiography and MDCT findings were independently interpreted by a paediatric cardiologist and cardiac radiologist in terms of: (1) the drainage site of the common pulmonary vein, (2) stenosis of the vertical vein, and (3) the course of the atypical vessel into the systemic vein in the case of vertical vein stenosis. The findings from both modalities were correlated with the results obtained at surgery (n=22) or autopsy (n=1). RESULTS: In all patients, MDCT correctly depicted the drainage site of the common pulmonary vein, stenosis of the vertical vein and the course of the atypical vessel into the systemic vein (sensitivity 100%, specificity 100%). The specificity of echocardiography was 100% for the three defined findings. The sensitivity of echocardiography, however, was 87%, 71% and 0%, respectively. CONCLUSION: MDCT can facilitate the diagnosis of TAPVC in certain cases.

Preoperative serum angiopoietin-2 levels correlate with lymph node status in patients with early gastric cancer.

BACKGROUND: Lymph node metastasis is the most important factor to consider when deciding on the modality of resection in patients with early gastric cancer. The aim of the present study was to assess the relationship between preoperative serum angiopoietin-2, a lymphangiogenic growth factor, and lymph node metastasis in patients with early gastric cancer. METHODS: A total of 62 preoperative serum samples from patients diagnosed with early gastric adenocarcinoma, and 30 serum samples from healthy donors were obtained. The serum levels of angiopoietin-2 (Ang-2) were quantified by immunoassay. Intra- and peritumor lymphatic vessel density (I-LVD and P-LVD) were counted after immunohistochemical staining. The relationship between the serum Ang-2 levels and other prognostic variables (tumor size, histological type, depth of tumor invasion, I-LDV, P-LDV, presence of lymph node involvement, and distant metastasis) were then examined by univariate and multivariate linear regression analyses. RESULTS: The median serum levels of Ang-2 in patients were higher than those of healthy controls [311.1 ng/mL, interquartile range (IQR) 256.7-311.1 ng/mL versus 286.5 ng/mL, IQR 226.9-286.5 ng/mL; Mann-Whitney test, P = 0.016]. Eight patients had metastatic lymph nodes; the Ang-2 levels from the patients with metastatic lymph nodes were higher than from those with negative lymph nodes (297.5 ng/mL, IQR 251.1-385.8 ng/mL versus 416.0 ng/mL, IQR 337.1-485.5 ng/mL; Mann-Whitney test, P = 0.019). Elevated serum Ang-2 levels were associated with positive lymph node involvement and this finding was significant on univariate (P = 0.008) and multivariate logistic regression analysis (P = 0.011). CONCLUSION: Serum Ang-2 levels were clinically useful markers for lymph node metastasis in patients with early gastric cancer.

Supracardiac type total anomalous pulmonary venous connection (TAPVC) with oesophageal varices.

Oesophageal varices due to total anomalous pulmonary venous connection (TAPVC) is very rare. Additionally, the infradiaphragmatic type is the most common type of oesophageal varices due to TAPVC. Paraoesophageal varices due to stenosis of the vertical vein of supracardiac TAPVC has not previously been reported. We describe paraoesophageal varices developed as a result of a connection between the left lower pulmonary vein and the umbilicovitelline venous system because of stenosis of the proximal vertical vein in supracardiac type TAPVC in a 3-day-old female newborn who presented with general cyanosis, tachypnoea and dyspnoea.