Jose Ruiz

MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma

Peptide sequence homology between the gene product of human MUC4 and rat sialomucin complex (SMC) has recently been reported. Each contains a mucin subunit with antiadhesive activity linked to the plasma membrane by means of a transmembrane subunit with two epidermal growth factor (EGF)–like domains that act as ligand for ErbB2. This study investigates MUC4 and ErbB2 receptor expression in major and minor salivary gland mucoepidermoid carcinoma and correlates patterns of expression with clinical outcomes.

Host innate recognition of an intestinal bacterial pathogen induces TRIF-dependent protective immunity

TRIF signaling triggers the amplification of macrophage bactericidal activity sufficient to eliminate invading intestinal pathogens through the sequential induction of IFN-β and IFN-γ from macrophages and NK cells, respectively.

Endoscopic embolization with onyx prior to resection of JNA: a new approach.

OBJECTIVE To report a novel pioneering approach of endoscopic embolization (EE) and resection of juvenile nasopharyngeal angiofibroma (JNA) and describe all outcomes and results. METHODS Four patients presented to the University of Miami with repeated episodes of unilateral epistaxis diagnosed by fiberoptic and radiographic examination as nasal JNA. Subsequently, in conjunction with neurosurgery, endoscopic visualization was provided to perform intratumor needle insertion, through which the liquid embolic agent Onyx was infused to embolize the JNAs under fluoroscopic and endoscopic guidance. The day after EE, endoscopic resection was performed. Operating room time, estimated blood loss (EBL), and other intraoperative and post-operative results are reported and compared to published literature. RESULTS A total of 4 patients (all males), had EE of JNA and subsequent endoscopic resection between September 2008 and January 2009. Average EBL during surgery was 412.5 ml (range 150-800) with an average operating room time of 228 min (range 95-485). We experienced no bleeding from the tumor or its attachments, only from the approach. Two patients experienced mild numbness in the V2 distribution, which began to resolve one week post-operatively. No other complications were encountered. CONCLUSIONS This is the first published report of direct endoscopic embolization of JNA with Onyx. Although further studies are needed, it seems to provide a safe, less invasive alternative to traditional embolization and endoscopic resection, but must be done in cooperation with interventional neurosurgery to maximize its safety profile.

Endoscopic Management of Sinonasal Hemangiopericytoma

Objective. Sinonasal hemangiopericytomas (SNHPCs) are rare perivascular tumors with low-grade malignant potential. Traditionally, these tumors have been treated with open approaches such as lateral rhinotomy, Caldwell-Luc, or transfacial approaches. Increased experience with endoscopic management of benign and malignant sinonasal tumors has led to a shift in management of SNHPC. The authors present their experience in the largest series of patients with SNHPC managed endoscopically. Study Design and Setting. Case series at a tertiary care medical center. Subjects and Method. A retrospective chart review of all patients undergoing endoscopic management of SNHPC at the University of Miami between 1999 and 2008 was conducted. All endoscopic resections were performed with curative intent. Results. Twelve patients with the diagnosis of SNHPC were treated endoscopically. Mean age was 62.5 years (range, 51-83 years). There were 6 men and 6 women. The mean follow-up was 41 months (range, 15-91 months). Seven (58.3%) presented with nasal obstruction, whereas 4 (41.6%) had epistaxis as their initial presenting symptom. Preoperative angiography or embolization was not performed in any case. Mean estimated blood loss was 630 mL (range, 100-1500 mL). Six patients underwent endonasal endoscopic anterior skull base resection; 4 had complete endoscopic resection all with negative margins. None underwent postoperative adjuvant treatment. No recurrence or metastatic disease was observed in this patient population. Conclusion. Endoscopic management of SNHPC is a feasible approach and did not compromise outcomes in this experience. In this series, familiarity with advance endoscopic sinus surgery was necessary to manage these patients. Postoperative adjuvant therapy was not necessary in this cohort.

Human intestinal epithelial cells express interleukin-10 through Toll-like receptor 4-mediated epithelial-macrophage crosstalk

In the intestine, interaction between epithelial cells and macrophages (MΦs) create a unique immunoregulatory microenvironment necessary to maintain local immune and tissue homeostasis. Human intestinal epithelial cells (IECs) have been shown to express interleukin (IL)-10, which keeps epithelial integrity. We have demonstrated that bacterial signaling through Toll-like receptor (TLR) 4 induces 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) synthesis in intestinal MΦs by cyclooxygenase (Cox)-2 expression. Here, we show that TLR4 signaling generates crosstalk between IECs and MΦs that enhances IL-10 expression in IECs. Direct stimulation of TLR4 leads to the expression of IL-10 in IECs, while the presence of MΦs in a Transwell system induces another peak in IL-10 expression in IECs at a later time point. The second peak of the IL-10 expression is two times greater than the first peak. This late induction of IL-10 depends on the nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ that is accumulated in IECs by TLR4-mediated inhibition of the ubiquitin-proteasomal pathway. TLR4 signaling in MΦs in turn synthesizes 15d-PGJ2 through p38 and ERK activation and Cox-2 induction, which activates PPARγ in IECs. These results suggest that TLR4 signaling maintains IL-10 production in IECs by generating epithelial-MΦs crosstalk, which is an important mechanism in the maintenance of intestinal homeostasis mediated through host-bacterial interactions.

Effect of coblation polypectomy on estimated blood loss in endoscopic sinus surgery.

Background We conducted a pilot study comparing estimated blood loss (EBL) using coblation-assisted endoscopic sinus surgery (CAESS) where coblation is used to debulk nasal polyps before microdebridement with a traditional microdebrider technique in chronic rhinosinusitis (CRS) patients with sinonasal polyps undergoing endoscopic sinus surgery (ESS). Methods A retrospective analysis was performed at a tertiary care center on patients with nasal polyposis undergoing ESS between January 2008 and July 2008. The University of Miami CT staging system was used preoperatively to evaluate the extent of sinonasal disease. The duration of surgery, blood loss per minute, total EBL, and demographic data were collected. Results Twenty-one patients underwent nasal polypectomy/ESS using CAESS and 16 patients underwent nasal polypectomy/ESS using microdebridement. The two groups had comparable University of Miami CT staging scores (p > 0.05). The average EBL was 307.1 ± 169.8 mL using coblation compared with 627.8 ± 424.2 mL using microdebridement (p < 0.05). The average duration of surgery using coblation was 116.2 ± 41.7 minutes, compared with 125.3 ± 48.4 minutes using microdebridement (p > 0.05). The average blood loss per minute was 2.8 ±1.7 mL in the coblation group compared with 4.8 ± 2.1 mL in the microdebridement group (p < 0.05). Subgroup analyses showed a significant decrease in average EBL and EBL/minute to be only significant for revision cases (p < 0.05) and not for primary cases (p > 0.05). Conclusion Coblation-assisted nasal polypectomy/ESS is associated with a statistically significant lower EBL and blood loss per minute when compared with traditional microdebridement technique. Coblation represents a new device that can reduce blood loss in patients with nasal polyposis undergoing traditional revision ESS. Further prospective randomized trials are needed to validate these findings.

Coblation assisted endoscopic juvenile nasopharyngeal angiofibroma resection

To provide additional support for the use of coblation in the surgical treatment of juvenile nasopharyngeal angiofibroma (JNA) tumors. Coblation radiofrequency has been recently described in endoscopic sinus surgery for polyp and tumor resection from the sinuses to the skull base. This is a case series from our institution in which we safely and successfully treated three adolescent boys with JNA using the coblation assisted technique. The first case was the smallest of the cases (Radkowski stage IB) and was embolized pre-operatively. The second and third cases, both larger in size (Radkowski stage IIC and IIB) did not undergo pre-operative embolization. The total surgical times were 105, 160, and 150 min and the estimated blood losses were 150, 400, and 130 mL, respectively. This yielded a blood loss per minute rate of only 1.4, 2.5, and 0.9 mL/min for the respective cases. None of the three patients required post-operative blood transfusion, nasal packing, or hospitalization of greater than one day. Follow-up showed no complications and no recurrence in these patients. Coblation assisted transnasal endoscopic resection of JNA is a feasible technique that can dissect through and debulk JNA tumor, despite its extreme vascularity. The surgery can be performed with minimal morbidity and low intraoperative blood loss, even with non-embolized tumors up to Radkowski IIC. These finding further support complete resection of JNA tumors using minimally invasive coblation assisted techniques.

Triamcinolone acetonide protects auditory hair cells from 4-hydroxy-2,3-nonenal (HNE) ototoxicity in vitro.

Abstract Conclusion. Triamcinolone acetonide crystalline suspension (e.g. Volon A®) was not ototoxic to the auditory hair cells present within organ of Corti explants and protected them from an ototoxic molecule, i.e. 4-hydroxy-2,3-nonenal (HNE), that is produced within the organ of Corti as a result of oxidative stress-induced damage. Objectives. To test the corticosteroid, triamcinolone acetonide, for ototoxicity and otoprotective capacity in organ of Corti explants. Materials and methods. Organ of Corti explants excised from 4-day-old rats were the test system, HNE was the ototoxin challenge. Hair cell integrity counts were performed with fluorescent microscopy on fixed explants stained with FITC-labeled phalloidin. Statistical significance was set atp <0.05. Results. Triamcinolone acetonide did not affect hair cell integrity in the organ of Corti explants and it provided a high level of protection of hair cells against the ototoxic effects of a damaging level of HNE as determined by hair cell density counts.

Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells

OBJECTIVE: Test the ability of glutathione monoethy1 ester (GSHe) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE). STUDY DESIGN AND SETTING: Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSHe for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSHe otoprotection. RESULTS: HNE was toxic to hair cells at physiologically relevant levels, eg, 400 μm, and GSHe provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM. CONCLUSION: GSHe protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress). SIGNIFICANCE: Treatment with GSHe may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.

MiR-181a negatively regulates NF-κB signaling and affects activated B-cell-like diffuse large B-cell lymphoma pathogenesis

Distinct subgroups of diffuse large B-cell lymphoma (DLBCL) genetically resemble specific mature B-cell populations that are blocked at different stages of the immune response in germinal centers (GCs). The activated B-cell (ABC)-like subgroup resembles post-GC plasmablasts undergoing constitutive survival signaling, yet knowledge of the mechanisms that negatively regulate this oncogenic signaling remains incomplete. In this study, we report that microRNA (miR)-181a is a negative regulator of nuclear factor κ-light-chain enhancer of activated B-cells (NF-κB) signaling. miR-181a overexpression significantly decreases the expression and activity of key NF-κB signaling components. Moreover, miR-181a decreases DLBCL tumor cell proliferation and survival, and anti-miR-181a abrogates these effects. Remarkably, these effects are augmented in the NF-κB dependent ABC-like subgroup compared with the GC B-cell (GCB)-like DLBCL subgroup. Concordantly, in vivo analyses of miR-181a induction in xenografts results in slower tumor growth rate and prolonged survival in the ABC-like DLBCL xenografts compared with the GCB-like DLBCL. We link these outcomes to relatively lower endogenous miR-181a expression and to NF-κB signaling dependency in the ABC-like DLBCL subgroup. Our findings indicate that miR-181a inhibits NF-κB activity, and that manipulation of miR-181a expression in the ABC-like DLBCL genetic background may result in a significant change in the proliferation and survival phenotype of this malignancy.