Recurrent Loss Research Articles

Abstract 92: Integrated analysis of copy number, sequence variant and gene expression data in kidney chromophobe cohort

Abstract The Cancer Genome Atlas (TCGA) contains various types of genomic data from a wide variety of cancers, including several rare tumor types. Here we analyze copy number, sequence variant and RNA-Seq data from TCGA for kidney chromophobe (KICH). Level 1 (raw) data, rather than Level 3 (segmented) data, from TCGA was used for an integrated analysis of copy number and gene expression profiles of the two cancers. Using the copy number and SNP probes, re-processed tumor profiles were more consistent with a control set in terms of median number of copy number events, sample ploidy, and breakpoint genes than with the published level 3 TCGA data. Probe-level data were analyzed using Nexus Copy Number SNP-FASST2 algorithm (a multi-state HMM algorithm), with systematic correction applied to correct for GC biases. Additionally we performed manual baseline adjustment to correct for sample ploidy based on whole-genome B-allele frequency data for each sample. Overall, the median number of copy number events in the KICH TCGA data set was reduced from 408 (in the level 3 set) to 85. After manual inspection, more than 87% of the TCGA KICH samples available at level 3 were found to have incorrect baseline ploidy assignments. Given KICH samples are known to have low ploidy overall, this step was critical for downstream analysis. RNA-Seq results for the entire cohort were evaluated to obtain normalized relative RNA expression. Somatic sequence variation results from whole exome sequencing and relative RNA expression were integrated with the individual copy number profiles to yield integrated per-sample results across all three data modalities. Aggregate analysis indicates highly recurrent losses (50-85% of samples) on chromosomes 1, 2, 6, 10, 13, 17 and 21. Lower level recurrent losses (∼15-20% of samples) were identified on chromosomes 3, 5, 8, 9, 11 and 18. Concordance analysis revealed statistically significant subsets of samples with co-occurring lower level recurrent losses. Aggregate sequence mutation analysis of chromosomes among 3, 5, 8, 9, 11 and 18 did not identify any mutational hotspots. Integration with RNA-Seq expression data from each tumor type revealed statistically significant correlations (p<0.05) with these copy number alterations, identifying potential driver genes of interest. Closer evaluation of copy number alteration and RNA-Seq expression at the individual sample level confirmed co-occurrence of significantly downregulated RNA expression within these regions of loss but no expression changes in samples without loss. This correlated with an overall difference in survival but was not statistically significant, given the overall small size of the data set. While still limiting in sample size, the TCGA KICH data series offers unique insight into a rare tumor type. Cross data integration for individual samples offers additional strength and validity to findings initially uncovered through traditional aggregate analysis. Citation Format: Andrea J. O’Hara, Zhiwei Che, Soheil Shams. Integrated analysis of copy number, sequence variant and gene expression data in kidney chromophobe cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 92.

たこつぼ型心筋症とrefeeding syndromeを併発し，2度の心停止を来した神経性食思不振症の1例(A case of two episodes of cardiopulmonary arrest caused by anorexia nervosa complicated with Takotsubo cardiomyopathy and refeeding syndrome)

要旨症例は22歳の女性。18歳頃から過食，嘔吐，極端なカロリー制限を繰り返していた。2か月前より1日300kcal以下にカロリーを制限し，意識障害を来して近医を救急受診した。低血糖を指摘され，ブドウ糖を投与された。翌日再度意識障害を来して同院を受診し，受診後心室細動に至ったが，心拍再開後当院に転院となった。来院時BMI 13.2kg/m2と著しく低下しており，心エコー検査上びまん性の壁運動低下を認めた。心電図上QTcは0.51秒と延長しており，その原因は心停止の影響もしくは神経性食思不振症（anorexia nervosa: AN）に伴うものと考えられた。来院同日，ICU入室後の心エコー検査では心基部の過収縮および心尖部の無収縮を認めた。第2病日再度心停止（pulseless electrical activity: PEA）となり，心肺蘇生法により心拍再開したが，血糖値は13mg/dLと低値であった。心血管造影上冠動脈に有意な狭窄はなかったが，左室造影にて心基部の過収縮と心尖部の無収縮を認め，たこつぼ型心筋症と診断した。その後，低血糖を防ぐために徐々に投与カロリーを増量したが，第4病日より低リン血症，汎血球減少を認め，refeeding syndrome（RS）と考えられる病態となったものの治療経過は良好で，第44病日当院精神科に転科した。ANにたこつぼ型心筋症が併発する要因として，低血糖が指摘されており，本症例も低血糖が誘因であったと思われる。また低血糖を来したことにより，投与カロリーを増量せざるを得ず，リンの投与が遅れたことがRSを生じた原因として考えられた。本症例の2回の心停止の原因は経過や検査所見より，QT延長やたこつぼ型心筋症などが関連した可能性が考えられた。ANに低血糖が生じた際には，たこつぼ型心筋症による循環不全および糖負荷によるRSの発症に十分に留意する必要がある。

Identification of recurrent focal copy number variations and their putative targeted driver genes in ovarian cancer.

BackgroundGenomic regions with recurrent DNA copy number variations (CNVs) are generally believed to encode oncogenes and tumor suppressor genes (TSGs) that drive cancer growth. However, it remains a challenge to delineate the key cancer driver genes from the regions encoding a large number of genes.ResultsIn this study, we developed a new approach to CNV analysis based on spectral decomposition of CNV profiles into focal CNVs and broad CNVs. We performed an analysis of CNV data of 587 serous ovarian cancer samples on multiple platforms. We identified a number of novel focal regions, such as focal gain of ESR1, focal loss of LSAMP, prognostic site at 3q26.2 and losses of sub-telomere regions in multiple chromosomes. Furthermore, we performed network modularity analysis to examine the relationships among genes encoded in the focal CNV regions. Our results also showed that the recurrent focal gains were significantly associated with the known oncogenes and recurrent losses associated with TSGs and the CNVs had a greater effect on the mRNA expression of the driver genes than that of the non-driver genes.ConclusionsOur results demonstrate that spectral decomposition of CNV profiles offers a new way of understanding the role of CNVs in cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1085-7) contains supplementary material, which is available to authorized users.

Value of videonystagmography and electrocochleography in prognosis prediction of patients with acute low-tone sensorineural hearing loss

Objective:To predict the prognosis of acute lowtone sensorineural hearing loss（ALHL）by using the videonystagmography(VNG) and electrocochleography(ECochG).Method:A retrospective study was done in 70 patients with ALHL after long-term follow-up. The recurrence rate and rate of progression to definite Meniere 's disease were determined according to the results of VNG and ECochG tests at the onset of the first episode of hearing loss.Result:Twentynine patients（41.4%）experienced recurrent hearing loss and 5 patients（7.1%）developed to Meniere's disease. In patients with an elevated SP/AP ratio and spontaneous nystagmus, the recurrence rate was 81.8%. However, in those with a normal SP/AP ratio and without spontaneous nystagmus, the recurrence rate was 23.3%.There was a statistically significant difference in the progression rate of Meniere's disease between the groups with(15.2%) and without spontaneous nystagmus.Conclusion:It has a certain reference value to predict prognosiswhen spontaneous nystagmus and an elevated SP/AP ratio are detected on initial examination in patients with ALHL.

Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia.

Neurophysiological basis of rapid eye movement sleep behavior disorder: informing future drug development.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism.

Community resilience to flood hazards in Khyber Pukhthunkhwa province of Pakistan

In Pakistan, floods are recurrent phenomenon and cause heavy loss to human life, standing crops and property. Community resilience is widely used in disasters and natural hazards. This paper aims to measure community resilience of a flood prone area in Khyber Pukhthunkhwa province of Pakistan. The flood resilience indicators were first determined through extensive literature review. The primary data regarding flood resilience indicators and community resilience were then collected through questionnaires. The indicators selected in this study were given proper weights using a subjective assessment method that ultimately resulted in community resilience indices. A total of 280 households from three sample sites of Charsadda, Nowshera and Peshawar were selected through the simple random sampling technique for questionnaire survey. The results showed that the overall composite community resilience indices as well as the component community resilience indices were very low for all the three sites. This study, therefore, recommends improvement in social, economic, institutional and physical indicators of the communities through preparedness, awareness, structural and non-structural measures. The proposed measures will enhance resilience of the communities and they would be able to cope with the future flood hazards.

GEOELECTRIC PARAMETERS AND ELEMENTAL COMPOSITIONS OF THE TOP SOIL OF CAMP AREA, ABEOKUTA, SOUTH WESTERN NIGERIA

Vertical Electrical Sounding (VES) and elemental composition surveys were carried out at twenty-two (22) sites atª¤? Camp Area, Alabata Road, Abeokuta, Southwestern Nigeria. This was with a view to determining depth to water«¤??bearing zones and extent of soil contamination thereby saving residents not just the pain of recurrent losses incurred for investing in dry wells, but also not to invest in contaminated waters. The study area is underlain by associated rock suites which includes pegmatite and quartz veins. Field data obtained was modeled and interpreted to obtain the geophysical parameters of the area and delineate the groundwater potential zones. Soil samples were also collected at the 22 VES points, at depths of 10 cm and 100 cm; the Global Positioning Satellite (GPS) equipment was used to obtain the geographical position of each sample point. Determination of the elemental composition of soil samples collected at the 10 cm and 100 cm depths was made using Atomic Absorption Spectrophotometer. Two heavy metals (Pb, and Cr), five major elements (K, Ca, N, P and Mg) and five trace elements (Zn, Mn, Cu, Al and Fe) were detected. It was observed that the values, representing the amount of the heavy metals, the major elements, and the trace elements were far less, mostly insignificant, at the 100 cm depth representing about the interface between the first and second layers in majority of the VES stations sampled, than at the 10 cm depth, representing the topsoil of the first layer. The implication of this is that the elements are not strictly domiciled within the area studied but may be due to runoffs as the area slopes down. Moreover, going by the values at the 100 cm depth, the elements may not be capable of percolating into the underground water zones in the area of study, and thus might not have contaminated the underground water. Thus, at the current level, the underground water can be adjudged safe for human consumption.ª¤?

Abstract P2-06-02: BIN3 is an 8p21 tumor suppressor regulating the epithelial attachment checkpoint

Abstract An important characteristic of multicellular organisms is the control that tissue architecture exerts on the growth and differentiation of individual cells. Epithelial cells sense their location through interactions with the extracellular matrix (ECM) as well as neighboring cells. These interactions generate input signals, including survival, that are critical to maintain tissue and cellular homeostasis. When attachment is compromised, epithelial cells undergo an intrinsically programmed cell death (apoptosis) that is termed anoikis (from the Greek "loss of home"). Importantly, failure to execute the anoikis program could result in adherent epithelial cells surviving in suspension or being able to proliiferate at sites different from their original environment. Thus, anoikis is a line of defense that must be circumvented by cancerous epithelial cells for them to leave their home niche, thrive in inappropriate ECM environments, and establish long distance metastases. Thus, elucidating how epithelial cancer cells escape anoikis is critical to understanding cancer progression. In order to uncover genes that modulate the anoikis response and are altered in human cancers, we performed a functional genomics study. We couple genome wide RNAi to identify gene functions that, when silenced, induce resistance to anoikis with a novel computational method, ISAR-DEL, specifically aimed at pinpointing candidate tumor suppressor genes based on recurrent loss of copy number. Our studies identified Bridging Integrator 3 (BIN3) as a novel tumor suppressor located on the chromosomal region 8p21.3, one of the most frequently lost regions in epithelial cancers. Mechanistically, we link BIN3 tumor suppression function to its ability to sense changes in the curvature of the cell membrane and relocate to the cell membrane after cell detachment to induce a proapoptotic cascade. Once BIN3 has translocated to the cell membrane it modulates the relocation and function of CDC42. In these conditions, CDC42 transmits the signal that leads to the activation of the stress protein P38-α and programmed cell death mediated by accumulation of the apoptotic facilitator BimEL. Overall, our results explain how changes in cell geometry are integrated in the cellular signaling network and present, for the first time, BIN3 as a novel breast cancer tumors suppressor. Citation Format: Silva J, Marshall N, Sanchez-Garcia F, Parsons R, Pe'er D. BIN3 is an 8p21 tumor suppressor regulating the epithelial attachment checkpoint. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-02.

Robust Recurrent Kernel Online Learning.

We propose a robust recurrent kernel online learning (RRKOL) algorithm based on the celebrated real-time recurrent learning approach that exploits the kernel trick in a recurrent online training manner. The novel RRKOL algorithm guarantees weight convergence with regularized risk management through the use of adaptive recurrent hyperparameters for superior generalization performance. Based on a new concept of the structure update error with a variable parameter length, we are the first one to propose the detailed structure update error, such that the weight convergence and robust stability proof can be integrated with a kernel sparsification scheme based on a solid theoretical ground. The RRKOL algorithm automatically weighs the regularized term in the recurrent loss function, such that we not only minimize the estimation error but also improve the generalization performance through sparsification with simulation support.

A paneukaryotic genomic analysis of the small GTPase RABL2 underscores the significance of recurrent gene loss in eukaryote evolution.

BackgroundThe cilium (flagellum) is a complex cellular structure inherited from the last eukaryotic common ancestor (LECA). A large number of ciliary proteins have been characterized in a few model organisms, but their evolutionary history often remains unexplored. One such protein is the small GTPase RABL2, recently implicated in the assembly of the sperm tail in mammals.ResultsUsing the wealth of currently available genome and transcriptome sequences, including data from our on-going sequencing projects, we systematically analyzed the phylogenetic distribution and evolutionary history of RABL2 orthologs. Our dense taxonomic sampling revealed the presence of RABL2 genes in nearly all major eukaryotic lineages, including small “obscure” taxa such as breviates, ancyromonads, malawimonads, jakobids, picozoans, or palpitomonads. The phyletic pattern of RABL2 genes indicates that it was present already in the LECA. However, some organisms lack RABL2 as a result of secondary loss and our present sampling predicts well over 30 such independent events during the eukaryote evolution. The distribution of RABL2 genes correlates with the presence/absence of cilia: not a single well-established cilium-lacking species has retained a RABL2 ortholog. However, several ciliated taxa, most notably nematodes, some arthropods and platyhelminths, diplomonads, and ciliated subgroups of apicomplexans and embryophytes, lack RABL2 as well, suggesting some simplification in their cilium-associated functions. On the other hand, several algae currently unknown to form cilia, e.g., the “prasinophytes” of the genus Prasinoderma or the ochrophytes Pelagococcus subviridis and Pinguiococcus pyrenoidosus, turned out to encode not only RABL2, but also homologs of some hallmark ciliary proteins, suggesting the existence of a cryptic flagellated stage in their life cycles. We additionally obtained insights into the evolution of the RABL2 gene architecture, which seems to have ancestrally consisted of eight exons subsequently modified not only by lineage-specific intron loss and gain, but also by recurrent loss of the terminal exon encoding a poorly conserved C-terminal extension.ConclusionsOur comparative analysis supports the notion that RABL2 is an ancestral component of the eukaryotic cilium and underscores the still underappreciated magnitude of recurrent gene loss, or reductive evolution in general, in the history of eukaryotic genomes and cells.ReviewersThis article was reviewed by Berend Snel and James O. McInerney.Electronic supplementary materialThe online version of this article (doi:10.1186/s13062-016-0107-8) contains supplementary material, which is available to authorized users.

NOTCH1, TP53, and MAP2K1 Mutations in Splenic Diffuse Red Pulp Small B-cell Lymphoma Are Associated With Progressive Disease.

Splenic diffuse red pulp small B-cell lymphoma (SDRPL) is considered an indolent neoplasm and its pathogenesis is not well known. We investigated the molecular characteristics of 19 SDRPL patients, 5 of them with progressive disease. IGHV genes were mutated in 9/13 (69%). Cytogenetic and molecular studies identified complex karyotypes in 2 cases, and IGH rearrangements in 3, with PAX5 and potentially TCL1 as partners in each one of them. Copy number arrays showed aberrations in 69% of the tumors, including recurrent losses of 10q23, 14q31-q32, and 17p13 in 3, and 9p21 in 2 cases. Deletion of 7q31.3-q32.3 was present in only 1 case and no trisomies 3 or 18 were detected. NOTCH1 and MAP2K1 were mutated in 2 cases each, whereas BRAF, TP53, and SF3B1 were mutated each in single cases. No mutations were found in NOTCH2 or MYD88. Four of the 5 patients with aggressive disease had mutations in NOTCH1 (2 cases), TP53 (1 case), and MAP2K1 (1 case). The progression-free survival of patients with mutated genes was significantly shorter than in the unmutated (P=0.011). These findings show that SDRPL share some mutated genes but not chromosomal alterations, with other splenic lymphomas, that may confer a more aggressive behavior.

Illumina next generation sequencing data and expression microarrays data from retinoblastoma and medulloblastoma tissues.

Retinoblastoma (Rb) is a pediatric intraocular malignancy and probably the most robust clinical model on which genetic predisposition to develop cancer has been demonstrated. Since deletions in chromosome 13 have been described in this tumor, we performed next generation sequencing to test whether recurrent losses could be detected in low coverage data. We used Illumina platform for 13 tumor tissue samples: two pools of 4 retinoblastoma cases each and one pool of 5 medulloblastoma cases (raw data can be found at http://www.ebi.ac.uk/ena/data/view/PRJEB6630).We first created an in silico reference profile generated from a human sequenced genome (GRCh37p5). From this data we calculated an integrity score to get an overview of gains and losses in all chromosomes; we next analyzed each chromosome in windows of 40 kb length, calculating for each window the log2 ratio between reads from tumor pool and in silico reference. Finally we generated panoramic maps with all the windows whether lost or gained along each chromosome associated to its cytogenetic bands to facilitate interpretation. Expression microarrays was done for the same samples and a list of over and under expressed genes is presented here. For this detection a significance analysis was done and a log2 fold change was chosen as significant (raw data can be found at http://www.ncbi.nlm.nih.gov/geo/accession number GSE11488). The complete research article can be found at Cancer Genetics journal (Garcia-Chequer et al., in press) [1]. In summary here we provide an overview with visual graphics of gains and losses chromosome by chromosome in retinoblastoma and medulloblastoma, also the integrity score analysis and a list of genes with relevant expression associated. This material can be useful to researchers that may want to explore gains and losses in other malignant tumors with this approach or compare their data with retinoblastoma.

Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis.

BackgroundThe genetic mechanisms underlying hemangioblastoma development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays and droplet digital PCR analysis to detect copy number variations (CNVs) in total of 45 hemangioblastoma tumors.ResultsWe identified 94 CNVs with a median of 18 CNVs per sample. The most frequently gained regions were on chromosomes 1 (p36.32) and 7 (p11.2). These regions contain the EGFR and PRDM16 genes. Recurrent losses were located at chromosome 12 (q24.13), which includes the gene PTPN11.ConclusionsOur findings provide the first high-resolution genome-wide view of chromosomal changes in hemangioblastoma and identify 23 candidate genes: EGFR, PRDM16, PTPN11, HOXD11, HOXD13, FLT3, PTCH, FGFR1, FOXP1, GPC3, HOXC13, HOXC11, MKL1, CHEK2, IRF4, GPHN, IKZF1, RB1, HOXA9, and micro RNA, such as hsa-mir-196a-2 for hemangioblastoma pathogenesis. Furthermore, our data implicate that cell proliferation and angiogenesis promoting pathways may be involved in the molecular pathogenesis of hemangioblastoma.

Inherited thrombophilia and reproductive disorders.

Apart from its established role in the pathogenesis of venous thromboembolism (VTE), inherited thrombophilia has been proposed as a possible cause of pregnancy loss and vascular gestational complications. There is a lot of controversy in the literature on the relationship between inherited prothrombotic defects and these obstetric complications. This is a review of the literature on inherited thrombophilia and reproductive disorders. Factor V Leiden, prothrombin G20210A mutation, and protein S deficiency seem to be associated with late and recurrent early pregnancy loss, while their impact on other pregnancy complications is conflicting. No definite association has been established between protein C and antithrombin deficiency and adverse pregnancy outcome, primarily due to their low prevalence. Screening is suggested only for women with early recurrent loss or late pregnancy loss. Anticoagulant treatment during pregnancy should be considered for women with complications who were tested positive for thrombophilia.

Amplification and overexpression of CTTN and CCND1 at chromosome 11q13 in Esophagus squamous cell carcinoma (ESCC) of North Eastern Chinese Population.

Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and is a major cause of cancer-related mortality. The combination of genetics, diet, behavior, and environment plays an important role in the carcinogenesis of ESCC. To characterize the genomic aberrations of this disease, we investigated the genomic imbalances in 19 primary ESCC cases using high-resolution array comparative genomic hybridization (CGH). All cases showed either loss or gain of whole chromosomes or segments of chromosome(s) with variable genomic sizes. The copy number alterations per case affected the median 34% (~ 1,034Mb/3,000Mb) of the whole genome. Recurrent gains were 1q21.3-qter, 3q13.11-qter, 5pter-p11, 7pter-p15.3, 7p12.1-p11.2, 7q11-q11.2, 8p12-qter, 11q13.2-q13.3, 12pter-p13.31, 17q24.2, 20q11.21-qter, and 22q11.21-q11.22 whereas the recurrent losses were 3pter-p11.1, 4pter-p12, 4q28.3-q31.22, 4q31.3-q32.1, 9pter-p12, 11q22.3-qter and 13q12.11-q22.1. Amplification of 11q13 resulting in overexpression of CTTN/CCND1 was the most prominent finding, which was observed in 13 of 19 ESCC cases. These unique profiles of copy number alteration should be validated by further studies and need to be taken into consideration when developing biomarkers for early detection of ESCC.

Three-Dimensional High-Definition Laparoscopic Treatment of Dunbar Syndrome (Celiac Axis Compression by Median Arcuate Ligament Hypertrophy) With Intra-Operative Laparoscopic Duplex Ultrasound Evaluation: Report of Two Cases

Introduction: Dunbar syndrome consists in a rare vascular disorder characterized by extrinsic compression of the celiac artery. This mechanic compression results in symptoms related to intermittent mesenteric ischemia. The goal of treatment is to release celiac artery compression and to restore vessel patency. Here we report two cases treated in our Surgical Department over the last four years. Case Report: A young female of 28 years-old, L.P., and 57-year-old men, E.G., both affected by recurrent post-prandial diffuse abdominal pain, diarrhea and weight loss came to our observation. A complete abdominal evaluation associated to radiologic exams made the diagnosis of CAC syndrome. Both patients were referred to a 3D laparoscopic surgical treatment of CACS with release of the median arcuate ligament. Vessels patency was checked intra-operatively using ecolaparoscopy. Conclusion: Median arcuate ligament section is the treatment of choice in Dunbar Syndrome, a rare vascular syndrome caused by extrinsic compression of the celiac trunk by a lower-inserted muscular bridge that connects the two crura of the diaphragm and crosses over the abdominal aorta. Minimally invasive 3D laparoscopic approach is ideal to treat Dunbar syndrome for the high definition and magnification of the 3D visualization. We perform an intraoperative laparoscopic duplex ultrasound investigation in the initial phase of the operation and at the conclusion of the procedure to assess the effectiveness of the treatment.

Case report of a Nigerian with ileocecal tuberculosis which mimicked Crohn's disease at colonoscopy

Both tuberculosis (TB) and Crohn's disease can affect any part of the gastrointestinal tract, but the terminal ileum and ileocecal region are mostly affected. Colonoscopic features of erythema, mucosal nodules, ulcers, strictures, and a deformed ileocecal valve occur in TB are nonspecific and can also occur in Crohn's disease. This is a case of a Nigerian with ileocecal TB, which mimicked Crohn's disease at colonoscopy. The patient is a 23-year-old man who presented to the clinic on account of recurrent abdominal pain and weight loss of 7 months duration. There was history of nonmucoid, nonbloody, and nonfoul smelling bowel motions. He had progressive weight loss was progressive with history of nausea, bloating, and anorexia but no vomiting. Colonoscopy revealed polypoid lesions in the cecum, deformed and polypoid ileocecal valve, and cobblestone appearance in the ileum. The histology of the ileal and colonic biopsies showed diffuse transmural infiltration by lymphocytic cells. Because of the extent of cecal and ileal involvement together with severe abdominal pain the patient was experiencing, he was taken for surgery where a right hemicolectomy with ileotransverse anastomosis was performed. The histology of the resected bowel then revealed features consistent with TB.

The Effects of Surgical Punctual Occlusion on Patients with Aqueous Deficient Dry Eye

Purpose: To analyze the improvement of symptoms and signs of dry eye after surgical punctual occlusion and to evaluate the effects of secondary systemic disease in dry eye patients. Methods: From March 2011 to July 2014, 15 eyes of 8 dry eye patients with a history of punctal plug insertion underwent surgical punctal occlusion. Schirmer test was measured based on mean 2.9 mm. The patients consisted of 4 dry eye patients with Sjogren’s disease, 1 with rheumatoid arthritis, 1 with graft-versus-host disease (GVHD), and 2 with no secondary systemic disease. Preoperative and postoperative ophthalmic examinations of log MAR visual acuity, subjective symptoms, corneal staining (National Eye Institute [NEI] score), and tear break-up time (BUT) were performed and the effects of secondary systemic disease in dry eye patients were evaluated. The results of surgical punctual occlusion were analyzed. Results: All patients showed a statistically significant improvement of log MAR visual acuity, subjective symptoms, corneal staining (NEI score), and tear BUT. The patients with rheumatoid-related diseases showed improved symptoms after surgery, but the patient with GVHD showed no significant improvement after surgery. Among the study patients, 80.0% showed completely closed punctum and 20.0% showed partial recanalization. Conclusions: Surgical punctal occlusion is an effective alternative in patients with severe aqueous deficient dry eye who show recurrent punctal plug loss or complications associated with punctal plugs. J Korean Ophthalmol Soc 2016;57(2):195-199

Speech-Language Disorders in Children with Hearing Loss Connected with Otitis Media with Effusion

Introduction: Otitis media with effusion is accompanied with conductive hearing loss. The aim of the study is to find out effect of long term or recurrent conductive hearing loss on speech descrimination. Method: Tonal audiometry timpanometry, speech audiometry (free sound field, head phone for left and right ear respectively) performed in 18 girls (mean age 8 years) and 27 boys (mean age 7 year). All of the children undergo speech/language screening tests. Results: Results of speech recognition showed no ear side effect in girls and right ear advantage in boys. Girls showed earlier in age central auditory processing disorder. Boys showed lower scores in words discrimination while hearing throught the head-phones on left ear. Poorer speech recognition at boys is accompanied with motorical immaturty, undeveloped articulation, poor vocabulary, lack of syntax in sentences, substitution of R and L, unable to focus on school tusk. Conclusion: Children with conductive hearing loss associated to otitis media with effusion are pronounced auditory processing disorder and speech/language discrimination disturbance. Associative thinking and solving of abstract problems are more affected in females than males.