Protective Effects of Purple Corn (Zea mays L.) Byproduct Extract on Blue Light-Induced Retinal Damage in A2E-Accumulated ARPE-19 Cells.

This study investigated the antioxidative characteristics of Zea mays L. purple corn cob and husk extract (PCHE) and its potential protective effects against blue light (BL)-induced damage in N-retinylidene-N-retinylethanolamine (A2E)-accumulated ARPE-19 retinal pigment epithelial cells. PCHE had a 2,2-diphenyl-1-picrylhydrazyl radical-scavenging capacity and Trolox equivalent antioxidant capacity of 1.28±0.43 mM Trolox equivalents (TE)/g and 2,545.41±34.13 mM TE/g, respectively. Total content of anthocyanins, polyphenols, and flavonoids in the PCHE was 11.13±0.10 mg cyanidin-3-glucoside equivalents/100 g, 227.90±7.38 mg gallic acid equivalents/g, and 117.75±2.46 mg catechin equivalents/g, respectively. PCHE suppressed the accumulation of A2E and the photooxidation caused by BL in a dose-dependent manner. After initial treatment with 25 µM/mL A2E and BL, ARPE-19 cells showed increased cell viability following additional treatment with 15 µg/mL PCHE while the expression of the p62 sequestosome 1 decreased, whereas that of heme oxygenase-1 protein increased compared with that in cells without PCHE treatment. This suggests that PCHE may slow the autophagy induced by BL exposure in A2E-accumulated retinal cells and protect them against oxidative stress.

Effects of lactic acid bacteria fermented feed and three types of lactic acid bacteria (L. plantarum, L. acidophilus, B. animalis) on intestinal microbiota and T cell polarization (Th1, Th2, Th17, Treg) in the intestinal lymph nodes and spleens of rats.

OBJECTIVE: In this study, we investigated the effects of Rubus coreanus-derived lactic acid bacteria (LAB) fermented feed (RC-LAB fermented feed) and three types of LAB (Lactobacillus plantarum, Lactobacillus acidophilus, Bifidobacterium animalis) on the expression of transcription factors and cytokines in Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens of rats. In addition, the effect on intestinal microbiota composition and body weight was investigated. METHODS: Five-week-old male rats were assigned to five treatments and eight replicates. The expression of transcription factors and cytokines of Th1, Th2, Th17, and Treg cells in the intestinal lymph nodes and spleens was analyzed using real-time reverse transcriptase polymerase chain reaction assays. Intestinal tract microbiota compositions were analyzed by next-generation sequencing and quantitative polymerase chain reaction assays. RESULTS: RC-LAB fermented feed and three types of LAB increased the expression of transcription factors and cytokines in Th1, Treg cells and Galectin-9, but decreased in Th2 and Th17 cells. In addition, the intestinal microbiota composition changed, the body weight and Firmicutes to Bacteroidetes (F/B) ratio decreased, and the relative abundance of LAB increased. CONCLUSION: LAB fermented feed and three types of LAB showed an immune modulation effect by inducing T cell polarization and increased LAB in the intestinal microbiota.

Intestinal microbial composition changes induced by Lactobacillus plantarum GBL 16, 17 fermented feed and intestinal immune homeostasis regulation in pigs.

In this study, Rubus coreanus (R. coreanus) byproducts with high polyphenol content were fermented with R. coreanus-derived lactic acid bacteria (Lactobacillus plantarum GBL 16 and 17). Then the effect of R. coreanus-derived lactic acid bacteria fermented feed (RC-LAB fermented feed) with probiotics (Bacillus subtills, Aspergillus oryzae, Yeast) as a feed additive for pigs on the composition of intestinal microbes and the regulation of intestinal immune homeostasis was investigated. Seventy-two finishing Berkshire pigs were randomly allotted to four different treatment groups and 18 replicates. RC-LAB fermented feed with probiotics increased the genera Lactobacillus, Streptococcus, Mitsuokella, Prevotella, Bacteroides spp., Roseburia spp., and Faecalibacterium prausnitzii, which are beneficial bacteria of the digestive tract of pigs. Also, RC-LAB fermented feed with probiotics decreased the genera Clostridium, Terrisporobacter, Romboutsia, Kandleria, Megasphaera and Escherichia, which are harmful bacteria. In particular, the relative abundance of the genera Lactobacillus and Streptococcus increased by an average of 8.51% and 4.68% in the treatment groups and the classes Clostridia and genera Escherichia decreased by an average of 27.05% and 2.85% in the treatment groups. In mesenteric lymph nodes (MLN) and spleens, the mRNA expression of transcription factors and cytokines in Th1 and Treg cells increased and the mRNA expression of Th2 and Th17 transcription factors and cytokines decreased, indicating a regulatory effect on intestinal immune homeostasis. RC-LAB fermented feed regulates gut immune homeostasis by influencing the composition of beneficial and detrimental microorganisms in the gut and regulating the balance of Th1/Th2 and Th17/Treg cells.

Galectin-9 Induced by Dietary Prebiotics Regulates Immunomodulation to Reduce Atopic Dermatitis Symptoms in 1-Chloro-2,4-Dinitrobenzene (DNCB)-Treated NC/Nga Mice.

Atopic dermatitis (AD) is a skin disorder that causes chronic itch. We investigated the inhibitory effects of a mixture of prebiotic short-chain galacto-oligosaccharides and long-chain fructooligosaccharides (scGOS/lcFOS), inulin, or ß-glucan on AD development in 1-chloro-2,4- dinitrobenzene (DNCB)-treated NC/Nga mice. Mice were randomly assigned to six groups: untreated mice, AD control, positive control (DNCB-treated NC/Nga mice fed a dietary supplement of Zyrtec), and DNCB-treated NC/Nga mice fed a dietary supplement of prebiotics such as scGOS/lcFOS (T1), inulin (T2), or ß-glucan (T3). The prebiotic treatment groups (T1, T2, and T3) showed suppression of AD symptoms, Th2 cell differentiation, and AD-like skin lesions induced by DNCB. In addition, prebiotic treatment also reduced the number of microorganisms such as Firmicutes, which is associated with AD symptoms, and increased the levels of Bacteroidetes and Ruminococcaceae, which are associated with alleviation of AD symptoms. Our findings demonstrate the inhibitory effects of prebiotics on AD development by improving the Th1/Th2 cytokine balance and beneficial symbiotic microorganisms in in vitro and in vivo models.

Oral Administration of ß-Glucan and Lactobacillus plantarum Alleviates Atopic Dermatitis-Like Symptoms.

Atopic dermatitis (AD) is a chronic inflammatory skin disease of mainly infants and children. Currently, the development of safe and effective treatments for AD is urgently required. The present study was conducted to investigate the immunomodulatory effects of yeast-extracted ß-1,3/1,6-glucan and/or Lactobacillus plantarum (L. plantarum) LM1004 against AD-like symptoms. To purpose, ß-1,3/1,6-glucan and/or L. plantarum LM1004 were orally administered to AD-induced animal models of rat (histamine-induced vasodilation) and mouse (pruritus and contact dermatitis) exhibiting different symptoms of AD. We then investigated the treatment effects on AD-like symptoms, gene expression of immune-related factors, and gut microbiomes. Oral administration of ß-1,3/1,6-glucan (0.01 g/kg initial body weight) and/or 2 × 1012 cells/g L. plantarum LM1004 (0.01 g/kg initial body weight) to ADinduced animal models showed significantly reduced vasodilation in the rat model, and pruritus, edema, and serum histamine in the mouse models (p < 0.05). Interestingly, ß-1,3/1,6- glucan and/or L. plantarum LM1004 significantly decreased the mRNA levels of Th2 and Th17 cell transcription factors, while the transcription factors of Th1 and Treg cells, galactin-9, filaggrin increased, which are indicative of enhanced immunomodulation (p < 0.05). Moreover, in rats with no AD induction, the same treatments significantly increased the relative abundance of phylum Bacteroidetes and the genus Bacteroides. Furthermore, bacterial taxa associated with butyrate production such as, Lachnospiraceae and Ruminococcaceae at family, and Roseburia at genus level were increased in the treated groups. These findings suggest that the dietary supplementation of ß-1,3/1,6-glucan and/or L. plantarum LM1004 has a great potential for treatment of AD as well as obesity in humans through mechanisms that might involve modulation of host immune systems and gut microbiota.

Anterior mediastinal Hodgkin lymphoma presenting as an extremely hypervascular tumor on computed tomography: A case report.

RATIONALE: In the thorax, Hodgkin lymphoma (HL) most frequently involves the anterior mediastinal and paratracheal regions and tends to spread to contiguous nodal groups. Enlarged lymph nodes typically have homogeneous soft tissue attenuation similar to that of muscle tissue on computed tomography (CT). PATIENT CONCERNS: A contrast-enhanced CT examination of a 19-year-old man with right-sided chest pain showed an intense, heterogeneously enhancing mass with organization of serpentine and dilated blood vessels in the right anterior mediastinum that had invaded the upper lobe of the right lung. DIAGNOSES: Following a wedge resection, histopathological examination showed Reed-Sternberg cells that were positive for CD-15 and CD-30, which is typical of HL. INTERVENTIONS: The patient was started treatment with 6 cycles of doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) regimen. OUTCOMES: After chemotherapy, the patient had shown a partial response to the treatment. LESSONS: This presentation of HL as an extremely hypervascular anterior mediastinal mass on CT imaging has not been previously reported in the literature. This case suggests that HL should be included in the differential diagnosis of a hypervascular anterior mediastinal mass, especially if the patient is a young adult.

Extragonadal germ cell tumor of the posterior mediastinum in a child complicated with spinal cord compression: a case report.

BACKGROUND: Germ cell tumors (GCTs) in children are rare neoplasms with diverse pathological findings according to the site and age of presentation. The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. Because of these nonspecific symptoms, it is difficult to suspect a mediastinal mass. A posterior mediastinal tumor causing spinal cord compression is an important example of an oncologic emergency arising from a neurogenic tumor. CASE PRESENTATION: Children with posterior mediastinum GCTs can be easily mistaken as having a neurogenic tumor because of site of tumor origin. We treated our 7-year-old patient with emergency decompression surgery and high-dose steroid pulse therapy to prevent secondary injury to the spinal cord. Primary injury was a result of spinal cord compression due to the initial manifestation of GCT in the posterior mediastinum. Cisplatin-based chemotherapy was also administered. The patient was followed up regularly for 3 years and is undergoing rehabilitation without any signs of recurrence. CONCLUSIONS: We present an extremely rare case of a child with paraparesis caused by extradural spinal cord compression as the initial manifestation of GCT in the posterior mediastinum. The child was treated with emergency decompression surgery and high-dose pulse steroid therapy to prevent secondary injury to the spinal cord.

Lynch syndrome-related small intestinal adenocarcinomas.

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

Use of a Comprehensive Geriatric Assessment to Predict Short-Term Postoperative Outcome in Elderly Patients With Colorectal Cancer.

PURPOSE: This study was conducted to identify the effectiveness of a preoperative comprehensive geriatric assessment (CGA) for predicting postoperative morbidity in elderly patients who underwent surgery for colorectal cancer. METHODS: Elderly patients (≥70 years old) who underwent surgery for colorectal cancer at a tertiary hospital in Korea were identified, and their cases were analyzed using data from a prospectively collected database to establish an association between major postsurgical complications and 'high-risk' patient as defined by the CGA. RESULTS: A total of 240 patients, with a mean age of 76.7 ± 5.2 years, were enrolled. Ninety-five patients (39.6%) were classified as "high-risk" and 99 patients (41.3%) as having postoperative complications. The univariate analysis indicated that risk factors for postoperative complications were age, American Society of Anesthesiologists physical status classification, serum hemoglobin, carcinoembryonic antigen, cancer stage, and "high-risk" status. The multivariable analyses indicated that "high-risk" status (odds ratio, 2.107; 95% confidence interval, 1.168-3.804; P = 0.013) and elevated preoperative carcinoembryonic antigen (odds ratio, 2.561; 95% confidence interval, 1.346-4.871, P = 0.004) were independently associated with postoperative complications. A multivariable analysis of the individual CGA domains indicated that high comorbidities and low activities of daily living were significantly related with postoperative complications. CONCLUSION: A preoperative CGA indicating "high-risk" was associated with major postoperative complications in elderly patients who underwent surgery for colorectal cancer. Thus, using the CGA to identify elderly colorectal-cancer patients who should be given more care during postoperative management may be clinically beneficial.

Erratum to: Prevalence of resistant hypertension and associated factors for blood pressure control status using Korean ambulatory blood pressure monitoring registry data.

[This corrects the article DOI: 10.1186/s40885-016-0045-x.].

MicroRNA-132 and microRNA-223 control positive feedback circuit by regulating FOXO3a in inflammatory bowel disease.

BACKGROUND AND AIM: Although many progresses have been achieved for inflammatory bowel disease (IBD), it is still remained as idiopathic disease to be completely controlled. MicroRNAs (miRNAs) have been identified as key players in many human diseases through degradation or translational inhibition of target genes. Because role of miRNAs in IBD is not completely understood yet, we need to identify miRNAs as novel targets for treatment of IBD. METHODS: Microarray analysis for miRNAs was performed using dextran sulfate sodium-induced colitis samples and selected differentially regulated miRNAs. Candidate genes were validated using in vitro system and IBD patient samples. Molecular mechanism for regulation of inflammatory signaling was identified using gene modulation system of miRNAs. RESULTS: We selected 14 upregulated and 15 downregulated miRNAs through microarray analysis. Among candidate miRNAs, significant upregulation of miR-132 and miR-223 was confirmed in inflamed mouse tissues as well as human IBD patient tissues. Through bioinformatics analysis, we identified FOXO3a as direct target of miRNAs and confirmed regulatory mechanism using luciferase assay. Expression of miRNAs clearly suppressed the level of IκBα through downregulation of FOXO3a, leading to enhanced NF-κB signaling to promote the production of pro-inflammatory cytokines. The downregulation of FOXO3a concurrent with upregulation of cytokines was significantly reversed by sequestration of miRNAs with miRNA sponges. CONCLUSIONS: Our findings provided the evidences that miR-132 and 223 are critical mediators in positive circuit for pathogenesis of IBD by negatively regulating FOXO3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for IBD treatment.

Increased Expression of Circulating Cancer Stem Cell Markers During the Perioperative Period Predicts Early Recurrence After Curative Resection of Hepatocellular Carcinoma.

BACKGROUND: This study was designed to investigate the correlation between postoperative recurrence of hepatocellular carcinoma (HCC) and perioperative expression and dynamic changes in cancer stem cell (CSC) markers in tumors and peripheral blood. METHODS: In HCC patients who underwent curative resection (n = 64) or liver transplantation (LT) (n = 17), mRNA levels for K19, EpCAM, and CD44 in peripheral blood and HCC tissues before and after operation were examined using real-time RT-PCR. Postoperative recurrence was analyzed in patients who underwent resection. Study participants were divided into high and low ratio groups, according to the ratio of postoperative to preoperative mRNA levels for each marker. RESULTS: K19 and CD44 mRNA levels in HCC tissues were higher in patients with recurrence than those without recurrence (p < 0.05 for all). Preoperative peripheral levels of K19 and EpCAM mRNA were higher in LT patients than in resection patients, and they were also significantly higher in cirrhotic patients of Child-Pugh Class B or C than those of Child-Pugh Class A (p < 0.05 for all). A high ratio of K19 mRNA was associated with lower relapse-free rate. Additionally, a high ratio for both K19 and CD44 mRNA was an independent poor prognostic factor for relapse-free survival (hazard ratio = 3.382, p = 0.016). CONCLUSIONS: Preoperative peripheral levels of K19 and EpCAM mRNA were influenced by background liver status and HCC. Additionally, the ratio of postoperative to preoperative mRNA levels for CSC markers, especially K19 and CD44, was shown to be important to predict HCC recurrence.

VAV3 Overexpressed in Cancer Stem Cells Is a Poor Prognostic Indicator in Ovarian Cancer Patients.

Ovarian carcinoma is a highly lethal malignancy due to frequent relapse and drug resistance. Cancer stem cells (CSCs) are thought to contribute significantly to disease relapse and drug resistance. In this study, a subpopulation of CSCs of ovarian carcinoma was isolated and the genes differentially expressed in these cells were identified to characterize CSCs and to find candidate biomarkers. Ovarian carcinoma cells from patients were primarily cultured, and spheroid-forming cells (SFCs) were isolated. The characteristic genes of SFCs were identified through cDNA microarray and validation by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association of their expression with clinicopathologic parameters was analyzed. GSC (4.26-fold), VAV3 (7.05-fold), FOXA2 (12.06-fold), LEF1 (17.26-fold), COMP (21.33-fold), GRIN2A (9.36-fold), CD86 (23.14-fold), PYY (4.18-fold), NKX3-2 (10.35-fold), and PDK4 (74.26-fold) were significantly upregulated in SFCs compared with parental cancer cells. With validation for human ovarian carcinomas, LEF1, PYY, NKX3-2, and WNT3A were significantly upregulated in chemoresistant cancers compared with chemosensitive cancers. Overexpression of LEF1, VAV3, and NKX3-2 was significantly associated with distant metastasis by immunohistochemistry. VAV3 overexpression was an independent poor survival indicator (hazard ratio=15.27, P<0.05) by multivariate Cox analysis. The further functional assay revealed that VAV3 knockdown regulated CSC activation and ovarian cancer cell proliferation and sensitized paclitaxel (PTX)-resistant cancer cells to PTX treatment. Taken together, we identified by high-throughput analysis of CSCs that VAV3 overexpression is a novel biomarker for poor prognosis and survival in ovarian carcinoma.

A case of nodular regenerative hyperplasia of the liver combined with toxic hepatitis.

Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.

Prevalence of resistant hypertension and associated factors for blood pressure control status with optimal medical therapy using Korean ambulatory blood pressure monitoring registry data.

BACKGROUND: Resistant hypertension (RH) may be one of the cause of the plateau in improving the control rate in hypertension (HT) management. The misdiagnosis of RH by clinic blood pressure (BP) is important clinical problem. Aim of the study were to investigate the prevalence of RH by ambulatory blood pressure monitoring (ABPM) and the factor associated with control status of ambulatory BPs. METHODS: For 1230 subjects taking one or more antihypertensive medication (AHM) enrolled in the Korean Ambulatory Blood Pressure Monitoring (Kor-ABP) registry, the prevalence of RH was calculated which was defined as uncontrolled BP by three AHM classes including diuretic or BP in need of four or more AHM classes. The prevalence determined by clinic versus ambulatory BP was compared. RESULTS: The age was 59.3 ± 12.5 years, and 44.3 % were female (n = 1230). Among them 72 subjects were taking three AHM drugs including diuretics and 105 subjects were taking four or more AHM classes. With uncontrolled daytime ambulatory BP in 41 among 72 subjects, prevalence of RH was 11.9 % (146/1230). By using nighttime BP criteria, there was significant difference in the prevalence of RH for clinic versus nighttime BP (146/177 vs. 159/177, p = 0.0124). For control status of daytime BP, masked uncontrolled BP was 16.9 % and controlled BP with white-coat effect was 14.1 %. For nighttime BP control status, odd ratios for smoking (0.624), drinking (1.512), coronary artery disease (0.604), calcium antagonist (1.705), and loop diuretics (0.454) were all significant. CONCLUSION: The prevalence itself was 11.9 % by daytime BP and it was significantly higher when using nighttime BP criteria. Control status of daytime BP was misclassified in 31.0 %. Smoking, drinking, coronary artery disease, calcium antagonist, and loop diuretics were associated with nighttime BP control status.

Orbital volume augmentation after injection of human orbital adipose-derived stem cells in rabbits.

PURPOSE: This randomized, controlled animal study investigated the morphologic and histologic properties of rabbit orbital fat following injection of human orbital adipose-derived stem cells (hoADSCs). METHODS: The efficacy of hoADSCs was compared to that of hyaluronic acid gel (HAG) and human orbital stromal vascular fraction (hoSVF). A total of 30 orbits from 15 New Zealand white rabbits (25 weeks postnatal, 2500-3000 g) underwent injection with HAG (molecular weight [MW] 1,000,000, 0.5 mL, n = 10, HAG only), hoSVF (0.25 mL) mixed with HAG (0.25 mL, n = 10, HAG + hoSVF), or hoADSCs (0.25 mL) mixed with HAG (0.25 mL, n = 10, HAG + hoADSCs). The degree of proptosis, and the time course of changes were determined and compared among groups. RESULTS: The difference between the initial exophthalmometric value and that at 4 weeks after injection was 1.77 mm for HAG only and 2.01 mm for HAG + hoSVF. The difference between the initial value and that at 12 weeks decreased to 0.05 mm for HAG only and 0.24 mm for HAG + hoSVF. In contrast, injection of HAG + hoADSCs increased the exophthalmometric value by 2.43 mm at 4 weeks after injection, and this difference was maintained at 2.56 mm at 12 weeks. Histopathologic examination revealed specific inflammation around the injection materials at 4 weeks after injection, and inflammation subsided 8 weeks after injection in all three groups. CONCLUSIONS: Thus, transplantation of hoADSCs with HAG is a safe and effective technique for orbital fat volume expansion. This is a new and promising method for orbital reconstruction and aesthetic orbital volume augmentation.

Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population.

Although inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab, the mechanisms mediating this resistance remain elusive. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrate that development of trastuzumab resistance in these cells is mediated by activation of an IL6 inflammatory feedback loop leading to expansion of the cancer stem cell (CSC) population. Long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL6 than parental cells. An IL6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies demonstrate that trastuzumab resistance may be mediated by an IL6 inflammatory loop and suggest that blocking this loop may provide alternative strategy to overcome trastuzumab resistance.

Expression of hMLH1, hMSH2 and hMSH6 in small intestinal carcinomas.

BACKGROUND/AIMS: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. METHODOLOGY: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). RESULTS: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. CONCLUSIONS: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).

A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the major primary liver cancers in adults. The phenotypic overlap between HCC and CC has been shown to comprise a continuous liver cancer spectrum. As a proof of this concept, a recent study demonstrated a genomic subtype of HCC that expressed CC-like gene expression traits, such as CC-like HCC, which revealed the common genomic trait of stem-cell-like properties and aggressive clinical outcomes. Scirrhous HCC (S-HCC), a rare variant of HCC, is characterized by abundant fibrous stroma and has been known to express several liver stem/progenitor cell markers. This suggests that S-HCC may harbor common intermediate traits between HCC and CC, including stem-cell traits, which are similar to those of CC-like HCC. However, the molecular and pathological characteristics of S-HCC have not been fully evaluated. By performing gene-expression profiling and immunohistochemical evaluation, we compared the morphological and molecular features of S-HCC with those of CC and HCC. S-HCC expresses both CC-like and stem-cell-like genomic traits. In addition, we observed the expression of core epithelial-mesenchymal transition (EMT)-related genes, which may contribute to the aggressive behavior of S-HCC. Overexpression of transforming growth factor beta (TGF-ß) signaling was also found, implying its regulatory role in the pathobiology of S-HCC. CONCLUSION: We suggest that the fibrous stromal component in HCC may contribute to the acquisition of CC-like gene-expression traits in HCC. The expression of stem-cell-like traits and TGF-ß/EMT molecules may play a pivotal role in the aggressive phenotyping of S-HCC. (HEPATOLOGY 2012;55:1776-1786).

A case of successful management of HHV-8⁺, EBV⁺ germinotropic lymphoproliferative disorder (GLD).

Human herpesvirus 8-positive (HHV-8⁺) and Epstein-Barr virus-positive (EBV⁺) germinotropic lymphoproliferative disorder (GLD) is extremely rare and occurs most commonly in immunocompetent persons who are human immunodeficiency virus (HIV)-seronegative. It is also recognized as a favorable response to conventional chemotherapy. Here, we report a case of a 75-year-old man with an incidentally found mass in the neck, compatible with GLD, which was detected by positron emission tomography (PET). Computed tomography (CT) scan, PET, and bone marrow studies showed only the left neck mass and no evidence of metastasis. Excisional biopsy of the mass was performed. The patient received four courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. After these treatments, he remained disease-free for 19 months. To the best of our knowledge, only five cases of HHV-8⁺, EBV⁺ GLD have been documented. This is the first such case report in Asia.