Anhydrous Alum Inhibits α-MSH-Induced Melanogenesis by Down-Regulating MITF via Dual Modulation of CREB and ERK.

Melanogenesis, the intricate process of melanin synthesis, is central to skin pigmentation and photoprotection and is regulated by various signaling pathways and transcription factors. To develop potential skin-whitening agents, we used B16F1 melanoma cells to investigate the inhibitory effects of anhydrous alum on melanogenesis and its underlying molecular mechanisms. Anhydrous alum (KAl(SO4)2) with high purity (>99%), which is generated through the heat-treatment of hydrated alum (KAl(SO4)2·12H2O) at 400 °C, potentiates a significant reduction in melanin content without cytotoxicity. Anhydrous alum downregulates the master regulator of melanogenesis, microphthalmia-associated transcription factor (MITF), which targets key genes involved in melanogenesis, thereby inhibiting α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. Phosphorylation of the cAMP response element-binding protein, which acts as a co-activator of MITF gene expression, is attenuated by anhydrous alum, resulting in compromised MITF transcription. Notably, anhydrous alum promoted extracellular signal-regulated kinase phosphorylation, leading to the impaired nuclear localization of MITF. Overall, these results demonstrated the generation and mode of action of anhydrous alum in B16F1 cells, which constitutes a promising option for cosmetic or therapeutic use.

Cross-Sectional Area of the Median Nerve as a Prognostic Indicator in Carpal Tunnel Syndrome Treated With Local Steroid Injection.

PURPOSE: Local steroid injection is an effective treatment modality for carpal tunnel syndrome. This study aimed to investigate the success rate of ultrasonography-guided local steroid injection and determine the prognostic value of the cross-sectional area (CSA) of the median nerve for steroid injection. METHODS: We retrospectively evaluated 40 patients with carpal tunnel syndrome whose median nerve CSA was >15 mm2 (large-CSA group; n = 16) or ≤15 mm2 (small-CSA group; n = 24). The CSA was measured using ultrasonography, and all the patients were treated with ultrasonography-guided corticosteroid injection. Demographic characteristics, symptoms, initial QuickDASH score, Boston Carpal Tunnel Questionnaires, and results of the nerve conduction study were assessed at baseline. Treatment success was defined in this study as the absence of symptom recurrence within the entire follow-up period. RESULTS: The treatment success rate was 45% (n = 18) after an average follow-up of 16 months. Overall, 11 patients (28%) underwent carpal tunnel release on an average of 11 months after steroid injection. The large-CSA group showed a significantly worse grade of electrodiagnostic testing at baseline than did the small-CSA group; however, there was no significant difference in final Boston Carpal Tunnel Questionnaires symptom score (1.7 vs 1.8, respectively) and the rate of continued treatment success at the last follow-up (42% vs 50%, respectively). The proportions of patients who required carpal tunnel decompression were 29% and 25% in the small-CSA and large-CSA groups, respectively. CONCLUSIONS: Local steroid injection for carpal tunnel syndrome has an overall success rate of 45% after a mean follow-up of 16 months. Preinjection CSA was not associated with whether the steroid injection was considered successful. This indicates that increased median nerve CSA does not preclude the possibility of symptomatic relief after a local steroid injection. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Arthroscopic cystectomy for Baker's cysts with and without one-way valve lesions: incidence of one-way valve lesion, associated pathologies, and clinical outcomes.

INTRODUCTION: A one-way valve lesion plays an important role in the formation of Baker's cysts and serves as an important landmark for accessing these cysts during arthroscopic surgery. This study aimed to investigate the incidence of one-way valve lesions and their effect on clinical outcomes in patients who underwent arthroscopic cystectomy for Baker's cysts. MATERIALS AND METHODS: Patients who underwent arthroscopic cystectomy for Baker's cysts between June 2005 and November 2017 were retrospectively reviewed. Patient demographic characteristics, radiologic/arthroscopic findings (presence of one-way valve lesions, concurrent chondral and meniscal lesions, and cyst wall thickness), and clinical outcomes (clinical recurrence rate, Lysholm score, and complications) at the 2-year follow-up were evaluated. Subgroup analysis was performed to compare clinical outcomes between patients with and without one-way valve lesions. RESULTS: Thirty patients (mean age, 57.4 ± 9.4 years) were included in this study. One-way valve lesions were surgically documented in 11 patients (36.7%). Ten patients (33.3%) had chondral lesions with an International Cartilage Repair Society grade ≥ 3, and 23 patients (76.7%) had concurrent chondral and meniscal lesions. At the 2-year follow-up, none of the patients had experienced clinical recurrence; the mean Lysholm score was 76.3 ± 17.5 (48-100). Three patients reported persistent pain, while two reported numbness or paresthesia. Subgroup analysis showed no significant differences in clinical recurrence rates, Lysholm scores, and complication rates between the groups. CONCLUSIONS: The incidence of one-way valve lesions during arthroscopic cystectomy for Baker's cysts was lower than that previously reported. Arthroscopic cystectomy showed good clinical results in patients with and without these lesions.

Effect of Residual Oxygen Concentration on the Lattice Parameters of Aluminum Nitride Powder Prepared via Carbothermal Reduction Nitridation Reaction.

Residual oxygen in wurtzite-type aluminum nitride (AlN) crystal, which significantly affects phonon transport and crystal growth, is crucial to thermal conductivity and the crystal quality of AlN ceramics. In this study, the effect of residual oxygen on the lattice of AlN was examined for as-synthesized and sintered samples. By controlling reaction time in the carbothermal reduction nitridation (CRN) procedure, AlN powder was successfully synthesized, and the amount of residual oxygen was systematically controlled. The evolution of lattice parameters of AlN with respect to oxygen conc. was carefully investigated via X-ray diffraction analysis. With increasing amounts of residual oxygen in the as-synthesized AlN, lattice expansion in the ab plane was induced without a significant change in the c-axis lattice parameter. The lattice expansion in the ab plane owing to the residual oxygen was also confirmed with high-resolution transmission electron microscopy, in contrast to the invariant lattice parameter of the sintered AlN phase. Micro-strain values from XRD peak broadening confirm that stress, induced by residual oxygen, expands the AlN lattice. In this work, the lattice expansion of AlN with increasing residual oxygen was elucidated via X-ray diffraction and HR-TEM, which is useful to estimate and control the lattice oxygen in AlN ceramics.

Development of prediction models for distinguishable cognitive trajectories in patients with amyloid positive mild cognitive impairment.

The clinical outcomes of patients with amyloid beta-positive (Aß+) mild cognitive impairment (MCI) are heterogeneous. We therefore developed prediction models for distinguishable cognitive trajectories in Aß+ participants with MCI. We included 238 Aß+ participants with MCI from the Alzheimer's Disease Neuroimaging Initiative to develop a group-based trajectory model and 63 Aß+ participants with MCI from the Samsung Medical Center for external validation. Three distinguishable classes, slow decliners (18.5%), intermediate decliners (42.9%), and fast decliners (38.7%), were identified. Intermediate decliners were associated with older age, higher AV45 standardized uptake value ratios (SUVR) and lower fluorodeoxyglucose (FDG) SUVR than slow decliners. Fast decliners were associated with older age, presence of APOE ε4, higher AV45 SUVR and lower FDG SUVR than slow decliners. Prediction models of cognitive decline showed good discrimination and calibration capabilities in the development and validation data sets. Our analysis yields novel insights into the cognitive trajectories of Aß+ patients with MCI, which will facilitate their effective stratification in Aß-targeted clinical trials.

Effect of the Plasma Gas Type on the Surface Characteristics of 3Y-TZP Ceramic.

Plasma surface treatment can be an attractive strategy for modifying the chemically inert nature of zirconia to improve its clinical performance. This study aimed to clarify the effect of plasma gas compositions on the physicochemical surface modifications of 3 mol% yttria-stabilized zirconia (3Y-TZP). The cold, atmospheric plasma discharges were carried out by using four different plasma gases, which are He/O2, N2/Ar, N2, and Ar from an application distance of 10 mm for 60 s. Static contact angles were measured to define the surface free energy. Changes in elemental composition, surface crystallinity, and surface topography were assessed with X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM), respectively. A significant decrease in water contact angle was observed in all plasma groups with the lowest value of 69° in the N2/Ar group. CLSM and SEM investigations exhibited no morphological changes in all plasma groups. XPS revealed that a reduction in the surface C content along with an increase in O content was pronounced in the case of N2/Ar compared to others, which was responsible for high hydrophilicity of the surface. XRD showed that the changes in crystallite size and microstrain due to oxygen atom displacements were observed in the N2/Ar group. The N2/Ar plasma treatment may contribute to enhancing the bioactivity as well as the bonding performance of 3Y-TZP by controlling the plasma-generated nitrogen functionalities.

Development and pilot implementation of an activity-based emotional support intervention for caregivers of children with cancer.

OBJECTIVE: This study aimed to pilot PAX ("Play, Act & Interact"), an activity-based emotional support intervention for caregivers of child with cancer, which focuses on addressing their psychological distress and post-traumatic stress symptoms (PTSSs). METHOD: Sixteen mothers whose children were child with cancer participated in this 4-week intervention. Their children (n = 16; 14 males; median age at diagnosis = 10.3 years; the median amount of time from diagnosis = 9 months) were at different treatment stages for a range of different diagnoses. Caregivers completed self-report instruments assessing their psychological distress including PTSSs and family functioning before and after the intervention and a brief open-response exit survey. Paired sample t-tests were computed to compare the pre-and post-intervention scores. RESULTS: The Post-traumatic Stress Disorder Checklist scores significantly decreased from pre- (M = 37.00, SD = 14.75) to post-intervention (M = 32.56, SD = 15.52), t(15) = 4.25, p < .001. There was also a significant difference between pre- (M = 33.5, SD = 3.18) and post-intervention (M = 35.7, SD = 3.14) scores on the Family Adherence subscale of the Family Adaptability and Cohesion Evaluation Scales III, t(15) = -2.58, p = .02. CONCLUSIONS: PAX was a promising intervention for supporting caregivers' PTSSs and family adaptability. Future studies investigating the long-term effects and replicating the current study with more participants and a control group are needed.

Does the long-term use of medial arch support insole induce the radiographic structural changes for pediatric flexible flat foot? - A prospective comparative study.

BACKGROUND: Several conservative treatment methods, from intrinsic muscle exercises to orthoses, including insoles or specially designed shoes, have been introduced for pediatric flexible flat foot (PFFF). However, the structural effects of a long-term use of medial arch support insole remain unclear because the normal physiological maturation of the medial longitudinal arch cannot be ruled out. METHODS: From January 2005 to June 2015, 18 patients (34 feet) in group 1 (continuously insole applied group) and 13 patients (26 feet) in group 2 (untreated group) were enrolled. Medial arch support insole was applied from the age 10-11years to radiographic physeal closure. RESULTS: In group 1, talonavicular coverage angle, lateral talo-1st metatarsal angle, calcaneal pitch angle and medial cuneiform height were significantly changed at final follow-up, although all values were still within the abnormal range. Further, no significant differences were found in any of the increments of the radiographic parameters between group 1 and 2. CONCLUSIONS: Radiographic improvements were found in both of medial arch support insole treated or untreated group despite all radiographic values were still within the abnormal range. It was meaningful that the PFFF could be improved somewhat until the physes were closed. And the hindfoot alignment remained unchanged regardless of medial arch support insole application.

Quantitative Validation of a Visual Rating Scale for Defining High-Iron Putamen in Patients With Multiple System Atrophy.

Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA). Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2* values and the volume of the entire putamen were measured. Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2* values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2* values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2* values ≥ third quartile, and the remaining patients. Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA.

Speculating the timing of iron deposition in the putamen in multiple system atrophy.

BACKGROUND & OBJECTIVE: Although iron accumulation is thought to be associated with neurodegenerative processes, the timing of putaminal iron deposition during the disease course of multiple system atrophy (MSA) remains unclear. We sought to investigate the temporal pattern of iron deposition in the putamen of MSA patients by calculating the conditional probabilities (CPs) of multimodal MRI changes. METHODS: We simultaneously measured putaminal R2*, volume and MD values of 39 probable MSA patients and 22 control subjects. The presence of significant MRI changes was defined as higher R2* and MD values, or lower volumes than cut-off values derived from mean values in control putamen. The CPs of R2* changes without MD or volume changes were then compared with those of MD or volume changes without R2* changes. RESULTS: Regardless of the cut-off values, the CPs of R2* increments without MD or volume changes were significantly lower than those for MD or volume changes without R2* increments. The associations of R2* with volume and MD values appeared in non-linear exponential and quadratic patterns, respectively. CONCLUSIONS: Our findings suggest that putaminal iron accumulation would occur under volume atrophy or MD increments. Thus, iron deposition in the putamen of MSA patients is likely a secondary byproduct of neurodegeneration.

The Brain Donation Program in South Korea.

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Tryptophan hydroxylase 1 and 5-HT7 receptor preferentially expressed in triple-negative breast cancer promote cancer progression through autocrine serotonin signaling.

BACKGROUND: Triple-negative breast cancer (TNBC) has a high risk of relapse and there are few chemotherapy options. Although 5-hydroxytryptamine (5-HT, serotonin) signaling pathways have been suggested as potential targets for anti-cancer drug development, the mechanism responsible for the action of 5-HT in TNBC remains unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively. Cell proliferation was measured using CellTiter 96 Aqueous One Solution. siRNA transfection was used to assess involvement of genes in cancer invasion, which were identified by Matrigel transwell invasion assay. Levels of 5-HT and vascular endothelial growth factor (VEGF) were measured using ELISA kits. Chick chorioallantoic membrane (CAM) assay and mouse tumor model were used to investigate the in vivo effects of SB269970, a 5-HT7 receptor antagonist, and BJ-1113, a novel synthetic compound. RESULTS: TNBC cell lines (MDA-MB-231, HCC-1395, and Hs578T) expressed higher levels of tryptophan hydroxylase 1 (TPH1) than hormone-responsive breast cancer cell lines (MCF-7 and T47D). In MDA-MB-231 cells, 5-HT promoted invasion and proliferation via 5-HT7 receptor, and interestingly, the stimulatory effect of 5-HT on MDA-MB-231 cell invasion was stronger than its effect on proliferation. Likewise, downstream signaling pathways of 5-HT7 differed during invasion and proliferation, that is, Gα-activated cAMP and Gßγ-activated kinase signaling during invasion, and Gßγ-activated PI3K/Akt signaling during proliferation. Also, 5-HT increased the protein expressions of TPH1 and VEGF in MDA-MB-231 cells. These results provide insight of the stimulatory effect of 5-HT on breast cancer progression; 5-HT was found to act more strongly during the first stage of metastasis (during invasion and migration) than during the later proliferative phase after local invasion. Interestingly, these actions of 5-HT were inhibited by BJ-1113, a 6-amino-2,4,5-trimethylpyridin-3-ol analog. BJ-1113 blocked intracellular signaling pathways initiated by 5-HT7 receptor activation, and exhibited anti-proliferative and anti-invasive activities against MDA-MB-231 cells. Furthermore, the inhibitory effect of BJ-1113 against MDA-MB-231 tumor growth was greater than that of SB269970, a 5-HT7 receptor antagonist. CONCLUSIONS: 5-HT7 receptor which mediates 5-HT-induced cancer progression is a potential therapeutic target in TNBC, and BJ-1113 offers a novel scaffold for the development of anti-cancer agents against TNBC.

A comparison between two methods for tumor localization during totally laparoscopic distal gastrectomy in patients with gastric cancer.

PURPOSE: The aim of this study was to compare two methods of tumor localization during totally laparoscopic distal gastrectomy (TLDG) in patients with gastric cancer. METHODS: From March 2014 to November 2014, patients in whom TLDG had been engaged for middle third gastric cancer enrolled in this study. The patients were allocated to either the radiography or endoscopy group based on the type of tumor localization technique. Clinicopathologic outcomes were compared between the 2 groups. RESULTS: The accrual was suspended in November 2014 when 39 patients had been enrolled because a failed localization happened in the radiography group. The radiography and endoscopy groups included 17 (43.6 %) and 22 patients (56.4 %), respectively. Mean length of the proximal resection margin did not differ between the radiography and endoscopy groups (4.0 ± 2.6 and 2.8 ± 1.2 cm, respectively; P = 0.077). Mean localization time was longer in the radiography group than in the endoscopy group (22.7 ± 11.4 and 6.9 ± 1.8 minutes, respectively, P < 0.001). There were no statistically significant differences in the incidence of severe complications between the 2 groups (5.9% and 4.5%, respectively, P = 0.851). CONCLUSION: As an intraoperative tumor localization for TLDG, radiologic method was unsafe even though other comparable parameters were not different from that of endoscopy group. Moreover, intraoperative endoscopic localization may be advantageous because it is highly accurate and contributes to reducing operation time.

BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway.

5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gßγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-HT-induced ROS generation and phosphorylation of PI3K/Akt but not of Src. Unlike NOX inhibitors, BJ-1108, which showed better antioxidant activity than vitamin C, barely suppressed superoxide anion induced by mevalonate or geranylgeranyl pyrophosphate which directly activates NOX without help from other signaling molecules in HUVECs, implying that the anti-angiogenic action of BJ-1108 was not mediated through direct action on NOX activation, or free radical scavenging activity. In conclusion, BJ-1108 inhibited 5-HT-induced angiogenesis through PI3K/NOX signaling but not through Src, ERK, or p38.

The Anti-Tumor Activity of Succinyl Macrolactin A Is Mediated through the ß-Catenin Destruction Complex via the Suppression of Tankyrase and PI3K/Akt.

Accumulated gene mutations in cancer suggest that multi-targeted suppression of affected signaling networks is a promising strategy for cancer treatment. In the present study, we report that 7-O-succinyl macrolactin A (SMA) suppresses tumor growth by stabilizing the ß-catenin destruction complex, which was achieved through inhibition of regulatory components associated with the complex. SMA significantly reduced the activities of PI3K/Akt, which corresponded with a decrease in GSK3ß phosphorylation, an increase in ß-catenin phosphorylation, and a reduction in nuclear ß-catenin content in HT29 human colon cancer cells. At the same time, the activity of tankyrase, which inhibits the ß-catenin destruction complex by destabilizing the axin level, was suppressed by SMA. Despite the low potency of SMA against tankyrase activity (IC50 of 50.1 µM and 15.5 µM for tankyrase 1 and 2, respectively) compared to XAV939 (IC50 of 11 nM for tankyrase 1), a selective and potent tankyrase inhibitor, SMA had strong inhibitory effects on ß-catenin-dependent TCF/LEF1 transcriptional activity (IC50 of 39.8 nM), which were similar to that of XAV939 (IC50 of 28.1 nM). In addition to suppressing the colony forming ability of colon cancer cells in vitro, SMA significantly inhibited tumor growth in CT26 syngenic and HT29 xenograft mouse tumor models. Furthermore, treating mice with SMA in combination with 5-FU in a colon cancer xenograft model or with cisplatin in an A549 lung cancer xenograft model resulted in greater anti-tumor activity than did treatment with the drugs alone. In the xenograft tumor tissues, SMA dose-dependently inhibited nuclear ß-catenin along with reductions in GSK3ß phosphorylation and increases in axin levels. These results suggest that SMA is a possible candidate as an effective anti-cancer agent alone or in combination with cytotoxic chemotherapeutic drugs, such as 5-FU and cisplatin, and that the mode of action for SMA involves stabilization of the ß-catenin destruction complex through inhibition of tankyrase and the PI3K/Akt signaling pathway.

Lessons learned from a comparative analysis of surgical outcomes of and learning curves for laparoscopy-assisted distal gastrectomy.

PURPOSE: Before expanding our indications for laparoscopic gastrectomy to advanced gastric cancer and adopting reduced port laparoscopic gastrectomy, we analyzed and audited the outcomes of laparoscopy-assisted distal gastrectomy (LADG) for adenocarcinoma; this was done during the adoptive period at our institution through the comparative analysis of short-term surgical outcomes and learning curves (LCs) of two surgeons with different careers. MATERIALS AND METHODS: A detailed comparative analysis of the LCs and surgical outcomes was done for the respective first 95 and 111 LADGs performed by two surgeons between July, 2006 and June, 2011. The LCs were fitted by using the non-linear ordinary least squares estimation method. RESULTS: The postoperative morbidity and mortality rates were 14.6% and 0.0%, respectively, and there was no significant difference in the morbidity rates (12.6% vs. 16.2%, P=0.467). More than 25 lymph nodes were retrieved by each surgeon during LADG procedures. The LCs of both surgeons were distinct. In this study, a stable plateau of the LC was not achieved by both surgeons even after performing 90 LADGs. CONCLUSIONS: Regardless of the experience with gastrectomy or laparoscopic surgery for other organs, or the age of surgeon, the outcome was quite acceptable; the learning process differ according to the surgeon's experience and individual characteristics.

Should lymph node micrometastasis be considered in node staging for gastric cancer?: the significance of lymph node micrometastasis in gastric cancer.

BACKGROUND: In TNM staging system, lymph node staging is based on the number of metastatic lymph nodes in gastric cancer and micrometastasis is not considered. Several reports proposed the importance of lymph node micrometastasis as the causative factor for recurrence and poor survival, but it remains controversial among researchers. METHODS: A total of 482 gastric cancer patients who underwent curative resection from 2004 to 2010 at Korea University Medical Center Ansan Hospital, South Korea were prospectively enrolled. For detecting lymph node micrometastasis, immunohistochemical staining with anti-cytokeratin antibody (CAM 5.2) was performed on negative lymph nodes by hematoxylin-eosin (H-E) staining. Survival differences were compared between conventional node staging and new node staging that took micrometastasis into consideration. Also, the prognostic value of lymph node micrometastasis was investigated in multivariate analysis. RESULTS: A total of 156 patients (32.4%) showed lymph node micrometastasis. Overall, the micrometastatic group had more advanced tumor and lymph node stage, lymphovascular cancer cell invasion, a higher rate of recurrence, and poor survival. Furthermore, when the cumulative numbers of macro- and micrometastatic lymph nodes were calculated together, the discriminative power of survival difference between each node stage became more stratified. Also, multivariate analysis using Cox's proportional hazards model demonstrated perineural invasion, pathologic T stage, dissected lymph nodes, macro- and micrometastatic lymph nodes are independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis was clinically significant as a risk factor for recurrent gastric cancer. Lymph node micrometastasis should be considered when estimating TNM stage for determining prognosis and the best treatment strategy.

Primary gastric malignant melanoma mimicking adenocarcinoma.

We report a case of primary gastric malignant melanoma that was diagnosed after curative resection but initially misdiagnosed as adenocarcinoma. A 68-year-old woman was referred to our department for surgery for gastric adenocarcinoma presenting as a polypoid lesion with central ulceration located in the upper body of the stomach. The preoperative diagnosis was confirmed by endoscopic biopsy. We performed laparoscopic total gastrectomy, and the final pathologic evaluation led to the diagnosis of primary gastric malignant melanoma without a primary lesion detected in the body. To the best of our knowledge, primary gastric malignant melanoma is extremely rare, and this is the first case reported in our country. According to the literature, it has aggressive biologic activity compared with adenocarcinoma, and curative resection is the only promising treatment strategy. In our case, the patient received an early diagnosis and underwent curative gastrectomy with radical lymphadenectomy, and no recurrence was noted for about two years.

Expression of intercellular adhesion molecule-1 and e-selectin in gastric cancer and their clinical significance.

PURPOSE: Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. MATERIALS AND METHODS: The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. RESULTS: In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). CONCLUSIONS: Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.