Subconjunctival Herniated Orbital Fat Mimicking Adipocytic Neoplasm.

PURPOSE: To describe and discuss rare and benign conditions of subconjunctival orbital fat herniation that may mimic adipocytic neoplasm. METHODS: Sixteen eyes of 13 patients with subconjunctival orbital fat herniation were included. They all underwent transconjunctival excision owing to cosmesis, discomfort, or suspicion of malignancy. Histopathologic examination, postoperative complications, and recurrent conditions were analyzed. RESULTS: Eleven male and two female patients were included. The lesion was unilateral in 10 and bilateral in 3 cases. Excision was performed via conjunctival wound and removing the prolapsed orbital fat. The conjunctiva was then closed with two to three interrupted sutures. All the histopathologic specimens revealed Lochkern cells, floret cells, and mature adipocytes separated by fibrovascular septae without hyperchromatic cells, consistent with subconjunctival herniated orbital fat. All the patients were treated successfully with transconjunctival excision without recurrence at an average follow-up of 10.6 months (range, 6 to 16 months). CONCLUSIONS: Prolapse of subconjunctival orbital fat is an uncommon entity of intraorbital masses and may mimic adipocytic neoplasm. It is usually associated with a dehiscence in the Tenon capsule. Surgical excision is indicated and pathologic evaluation is necessary if any malignancy is suspected.

Globo-H ceramide shed from cancer cells triggers translin-associated factor X-dependent angiogenesis.

Tumor angiogenesis is a critical element of cancer progression, and strategies for its selective blockade are still sought. Here, we examine the angiogenic effects of Globo-H ceramide (GHCer), the most prevalent glycolipid in a majority of epithelial cancers and one that acts as an immune checkpoint. Here, we report that GHCer becomes incorporated into endothelial cells through the absorption of microvesicles shed from tumor cells. In endothelial cells, GHCer addition induces migration, tube formation, and intracellular Ca(2+) mobilization in vitro and angiogenesis in vivo. Breast cancer cells expressing high levels of GHCer displayed relatively greater tumorigenicity and angiogenesis compared with cells expressing low levels of Globo-H. Clincally, GHCer(+) breast cancer specimens contained higher vessel density than GHCer(-) breast cancer specimens. Mechanistic investigations linked the angiogenic effects of GHCer to its endocytosis and binding to TRAX, with consequent release of PLCß1 from TRAX to trigger Ca(2+) mobilization. Together, our findings highlight the importance of GHC as a target for cancer therapy by providing new information on its key role in tumor angiogenesis.

Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population.

BACKGROUND: Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) as well as clinical presentations of each molecualr subtype in Han Chinese population. METHODS: In all, 169 breast cancer samples (44 from Taiwan and 125 from China) of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50) were retrieved for molecular subtype prediction. RESULTS: For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD) remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. CONCLUSIONS: We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective study with longer survival data is needed.

Promoter methylation status of HIN-1 associated with outcomes of ovarian clear cell adenocarcinoma.

BACKGROUND: This study is to analyze promoter methylation of various tumor suppressor genes in different types of ovarian carcinoma and to identify potential therapeutic targets of ovarian clear cell adenocarcinoma (OCCA). MATERIALS AND METHODS: The promoter methylation statuses of 40 genes in primary ovarian carcinomas including 47 clear- and 63 non-clear-cell type tissues, 6 OCCA cell lines, 29 benign ovarian endometriotic cysts, and 31 normal controls were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The MS-MLPA results were correlated with clinicopathological features and outcomes of 47 OCCA patients. Functions of the target genes were further explored by Western Blot Analysis, apoptosis assay, and caspase-3/7 activity analysis. RESULTS: Frequencies of methylated RASSF1A, CDH13, CACNA1A, HIN-1, and sFRP5 genes in OCCA tissues were significantly higher than those in non-OCCA cancerous tissues and benign endometriotic cysts. The expected OS for patients with methylated promoters of HIN-1 was significantly worse than those for patients without methylated HIN-1 (30% vs. 62%, p = 0.002). The HIN-1 gene was over-expressed in ES2 cells, a significant reduction in cell growth and induction of apoptosis, and increasing paclitaxel sensitivity by reducing phosphorylation of Akt were observed. CONCLUSIONS: Methylation of HIN-1 promoter is a novel epigenetic biomarker associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity which is partly through Akt pathway.

Reliability and effectiveness of GEWF solution in the identification of lymph nodes in specimens of colorectal carcinoma.

Lymph node status is pivotal in the staging process of cancer. With regards to colorectal cancer, lymph node retrieval is always laborious. Sometimes, it is also a challenge to recover a minimum of 12 lymph nodes from the pericolorectal tissue. Among many proposed adjunctive solutions, GEWF solution (glacial acetic acid, ethanol, distilled water, and formaldehyde) has been introduced recently and suggested to be superior. To further evaluate its efficiency, the pericolorectal tissue, which has been reexamined extensively in the conventional condition, was refixed into GEWF solution in this study. More lymph nodes were found in 75% (n = 6) of the 8 experimental cases, and 50% (n = 4) of them had 12 or more yielded lymph nodes eventually. In addition, no adverse influences on the expressions of immunohistochemical and special stains were seen. These data support the reliability and effectiveness of GEWF solution in improvement of lymph node yield.

Podocalyxin EBP50 ezrin molecular complex enhances the metastatic potential of renal cell carcinoma through recruiting Rac1 guanine nucleotide exchange factor ARHGEF7.

Podocalyxin was initially identified in glomerular podocytes to critically maintain the structural and functional integrity of the glomerular ultrafiltrative apparatus. Lately, it has emerged as a malignant marker in tumors arising from a variety of tissue origins. By immunohistochemistry, we identified that 9.6% of renal cell carcinoma patients overexpress this protein. This subset of patients had significantly shorter disease-specific and overall survivals, and, importantly, we established podocalyxin overexpression as an independent prognostic factor for latent distant metastasis with multivariate analysis. Podocalyxin down-regulation by small interfering RNA led to defective migration in model renal tubular cells, which was corrected by re-expression of podocalyxin. The activity of the small GTPase Rac1, a well-characterized modulator of cell migration, was diminished by podocalyxin knock-down. Conversely, podocalyxin overexpression in human embryonic kidney cells up-regulated Rac1 activity, which depended on a complex formed by podocalyxin, ERM-binding phosphoprotein 50, ezrin, and ARHGEF7, a Rac1 activator. Therefore, podocalyxin can serve as a biomarker to identify renal cell carcinoma patients with higher metastatic potential for more aggressive intervention at earlier clinical stages.

Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age. METHODS: The quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues. RESULTS: The analysis of 45 younger CRC patients (age

Subclinical histologic chorioamnionitis and related clinical and laboratory parameters in preterm deliveries.

BACKGROUND: Histologic chorioamnionitis (HCA) is associated with preterm delivery and with neonatal morbidity and mortality. Because HCA is usually subclinical, histologic examination of the placenta is essential for confirmatory diagnosis. In the present study, the correlations between subclinical HCA and relevant clinical and laboratory parameters were analyzed. METHODS: This was a retrospective study. We reviewed the placental histopathologic findings and the charts of patients who were admitted to our neonatal intensive care unit after delivery and their mothers between January 2007 and March 2008. A total of 77 preterm infants [gastational age (GA): 32.2 3.4 weeks, birth weight (BW): 1718 +/- 554 g] were categorized as group A with histologic evidence of placental inflammation (n=27) or group B without histologic evidence of placental inflammation (n=50). Placental histology was studied to identify the presence of inflammatory states such as chorioamnionitis, funisitis and deciduitis. Laboratory parameters including complete blood count, differential count, and C-reactive protein (CRP) level of mothers and initial arterial blood gas, glucose Level and mean blood pressure of the infants were documented. Gestational age, Apgar score, history of prolonged premature rupture of membrane (prolonged PROM), gestational diabetes mellitus, meconium-stained amniotic fluid, pregnancy-induced hypertension and signs of pre-eclampsia were also collected as clinical parameters. All data were analyzed using independent t tests and Fisher's exact test, as appropriate. RESULTS: Group A newborns had a significantly lower gestational age (30.8 +/- 4.1 weeks vs. 33.0 +/- 2.6 weeks, p < 0.05) and higher CRP level (0.56 +/- 0.92 mg/dL vs. 0.12 +/- 0.14 mg/dL, p < 0.05), together with higher maternal WBC count (13,002 +/- 4344/microL vs. 10,850 +/- 3722/microL, p < 0.05) and higher rate of prolonged PROM [14/27 (51.85%) vs. 8/37 (21.62%), p < 0.05] compared with group B newborns. CONCLUSION: We found that HCA was significantly correlated with lower gestational age, higher CRP level of preterm infants, higher maternal WBC count, and a higher rate of prolonged PROM. Our results demonstrate a significant association between HCA with an elevated CRP level in preterm infants. These findings further confirmed the association between maternal inflammation and preterm deliveries.

Multiple tumors of the follicular infundibulum.

BACKGROUND: Tumor of the follicular infundibulum is an uncommon benign neoplasm manifested histopathologically by a superficial epithelial plate-like growth pattern with multiple thin epidermal connections comprised of monomorphic cells with abundant cytoplasm. Cases of multiple tumors of the follicular infundibulum are rare and are described as hypopigmented scar-like macules or flat papules on the face, neck, and upper chest. OBJECTIVE: The objective was to describe a case of multiple tumors of the follicular infundibulum with numerous pigmented macules or papules and extensive involvement including the face, neck, anterior and posterior trunk, upper extremities, and intertriginous areas. METHODS: A case report and literature review are presented. CONCLUSION: Tumor of the follicular infundibulum with its characteristic histopathologic manifestations is a well-recognized entity nowadays. Our case further expands the constellation of the clinical presentation of the multiple variant. Although the possibility of malignant basocellular degeneration seems remote, the multiplicity of the lesions, the possibility of clinical overlook, and the impracticality of complete treatment makes regular follow-up rational.

Endoscopic potassium-titanyl-phosphate laser treatment for the reduction of hypertrophic inferior nasal turbinate.

OBJECTIVE: This study investigated the efficacy of using the KTP/532 laser in endoscopic inferior turbinate reduction surgery. BACKGROUND DATA: Potasium-titanyl-phosphate (KTP/532) laser is a useful tool in endoscopic intranasal operations, due to its outstanding capabilities in hemostasis, tissue penetration, and the maneuverability of its flexible transmission optic fiber. MATERIALS AND METHODS: A total of 124 patients (male/female 73:51, mean age 38.7 +/- 12.3 years) with chronic hypertrophic rhinitis who received endoscopic KTP/532 laser inferior turbinate reduction surgery (7 Watts, continuous mode, 0.6-1-mm spots) were available for follow-up (mean follow-up period, 25.1 +/- 7.3 months). Medical records were retrospectively reviewed, and patients were interviewed with a questionnaire. RESULTS: The KTP/532 laser was excellent in relieving nose obstruction caused by inferior turbinate hypertrophy; 87% of patients reported improvement. The outcomes were less promising in reducing post-nasal drip; 12.9% reported only some improvement. Under intranasal endoscopy, the risk of postoperative bleeding and complication was low. CONCLUSION: The findings proved that, with the use of an endoscope, the KTP/532 laser appears to be an excellent alternative for treating hypertrophic inferior turbinate.