COX-2 Overexpression in Schneiderian Papillomas.

BACKGROUND: Schneiderian papillomas (SP) are aggressive sinonasal tumors that occasionally extend into areas that are surgically unresectable. OBJECTIVE: evaluate the signifcance of cyclo-oxygenase-2 (COX-2) expression in SP. METHODS: Immunohistochemistry for COX-2 was performed on SP samples and middle turbinates from chronic rhinosinusitis without nasal polyps controls obtained during surgical resection between 2009-2017. A positive stain was defined as having 10% or more cells exhibiting diffuse immunoreactivity. Comparisons were performed using Fisher Exact tests, t-tests, and ANOVA. RESULTS: The study included 67 tumor samples and 9 controls from two academic institutions. The mean age of the SP group was 55.4 years and 53.2 years in the control group (p = 0.71). Thirty-nine (58.2%) SP patients had previous surgery compared to 1 (11.1%) in the control group (p = 0.01). The most common tumor attachment sites were the maxillary (47.8%) and ethmoid (25.4%) sinuses. Fifteen (22.4%) SP samples stained strongly positive for COX-2 and 24 (35.8%) stained weakly positive compared to no positive stains in the control group (p < 0.01). When stratified by COX-2 intensity, there were no statistically significant differences in gender, smoking history, history of previous sinus surgery, site of attachment, papilloma subtype, or future recurrence between SP samples. CONCLUSION: COX-2 was overexpressed in 58.2% of SP cases, and strongly positive in 22.4% of cases, compared to no positive staining among controls. No significant differences in COX-2 expression were observed between SP subtypes or recurrent tumors. Further studies are warranted to evaluate COX-2 as a possible therapeutic target in tumors that overexpress the enzyme.

A budding case of infectious endocarditis: Candida lusitaniae.

This is a case of recurrent Candida lusitaniae prosthetic valve endocarditis with budding yeast and pseudohyphae on the histopathology. This case illustrates the importance of keeping vigilant in recognizing some of the emerging drug resistant Candida species in our practice.

Churg-Strauss Syndrome Presenting as Acute Necrotizing Eosinophilic Myocarditis: Concise Review of the Literature.

BACKGROUND: Acute eosinophilic myocarditis (EM) is a rare form of heart failure that is characterized by myocardial eosinophilic infiltration usually in association with peripheral eosinophilia. The underlying cause is variable and can include allergic reactions, parasitic infection, idiopathic hypereosinophilic syndrome, malignancy, Loeffler's syndrome, Churg-Strauss syndrome (CSS), early giant cell myocarditis and malignancy. The course is potentially fatal, and early diagnosis and treatment with steroids is essential. CONCLUSION: Here, we present an illustrative case of eosinophilic myocarditis secondary to CSS followed by a brief review of epidemiology, pathogenesis, diagnosis and treatment of both disease entities.

Botulinum toxin to improve vessel graft patency in cerebral revascularization surgery: report of 3 cases.

Surgical revascularization continues to play an important role in the management of complex intracranial aneurysms and ischemic cerebrovascular disease. Graft spasm is a common complication of bypass procedures and can result in ischemia or graft thrombosis. The authors here report on the first clinical use of botulinum toxin to prevent graft spasm following extracranial-intracranial (EC-IC) bypass. This technique was used in 3 EC-IC bypass surgeries, 2 for symptomatic carotid artery occlusions and 1 for a ruptured basilar tip aneurysm. In all 3 cases, the harvested graft was treated ex vivo with botulinum toxin before the anastomosis was performed. Post-bypass vascular imaging demonstrated patency and the absence of spasm in all grafts. Histopathological analyses of treated vessels did not show any immediate endothelial or vessel wall damage. Postoperative angiograms were without graft spasm in all cases. Botulinum toxin may be a reasonable option for preventing graft spasm and maintaining patency in cerebral revascularization procedures.

Four 45 Gbps PAM4 VCSEL based transmission through 300 m wideband OM4 fiber over SWDM4 wavelength grid.

We demonstrate successful transmission of four 45 Gbps PAM4 single-channels through OM4 multimode fibers (MMFs) and wideband MMF using a PAM4 PHY chip and four vertical cavity surface emitting lasers (VCSELs) with wavelengths ranging over short wavelength division multiplexing (SWDM) grid. Real-time bit error ratios (BERs) < 2 × 10-4 were achieved for all four 45 Gbps PAM4 SWDM grid channels over 100 m, 200 m, and 300 m of wideband OM4 MMFs. All four channel received PAM4 optical eyes are shown after propagating through 100 m, 200 m, and 300 m of wideband OM4 as well as 100 m and 200 m conventional OM4 MMFs. The measured BERs as a function of the inner eye optical modulation amplitudes (OMAs) are shown for all four SWDM grid channels. Inner eye OMAs ranged from -16.2 dBm to -13.5 dBm for different channels over different OM4 MMF types at the KP4 BER threshold of 2 × 10-4.

10 Spatial mode transmission using low differential mode delay 6-LP fiber using all-fiber photonic lanterns.

To unlock the cost benefits of space division multiplexing transmission systems, higher spatial multiplicity is required. Here, we investigate a potential route to increasing the number of spatial mode channels within a single core few-mode fiber. Key for longer transmission distances and low computational complexity is the fabrication of fibers with low differential mode group delays. As such in this work, we combine wavelength and mode-division multiplexed transmission over a 4.45 km low-DMGD 6-LP-mode fiber by employing low-loss all-fiber 10-port photonic lanterns to couple light in and out of the fiber. Hence, a minimum DMGD of 0.2 ns (maximum 0.357 ns) is measured after 4.45 km. Instrumental to the multi-mode transmission system is the employed time-domain-SDM receiver, allowing 10 spatial mode channels (over both polarizations) to be captured using only 3 coherent receivers and real-time oscilloscopes in comparison with 10 for conventional methods. The spatial channels were unraveled using 20 × 20 multiple-input multiple-output digital signal processing. By employing a novel round-robin encoding technique, stable performance over a long measurement period demonstrates the feasibility of 10x increase in single-core multi-mode transmission.

Immunohistochemical panel to differentiate endometrial stromal sarcoma, uterine leiomyosarcoma and leiomyoma: something old and something new.

AIMS: To evaluate an immunohistochemical panel differentiating endometrial stromal sarcoma (ESS) from uterine leiomyosarcoma (ULMS) and leiomyoma (LM). METHODS: 94 cases (28 ESS, 41 ULMS, 25 LM) were retrieved and arrayed. 10 immunomarkers (estrogen receptor (ER), progesterone receptor (PR), CD10, smooth muscle actin, desmin, h-caldesmon, transgelin, GEM, ASC1, stathmin1) were used. A predictive model was constructed and examined by receiver operating characteristics curve analysis to determine area under the curve (AUC). RESULTS: The combination of ER(+)/PR(+)/CD10(+)/GEM(-)/h-caldesmon(-)/transgelin(-) can predict ESS versus ULMS with AUC predictive value of 0.872 (95% CI 0.784 to 0.961, p<0.0001). The combination of ER(+)/PR(+)/CD10(+)/h-caldesmon(-)/transgelin(-) can predict low grade (LG) ESS from 'LG' ULMS with AUC predictive value of 0.914 (95% CI 0.832 to 0.995, p<0.0001). Finally, ULMS and ESS, including the LGs, were more likely to be stathmin1(+) than LM. CONCLUSIONS: Due to the different clinical course and management, adding novel antibodies (GEM, transgelin) to the well established immunohistochemistry panel seemed to be useful in distinguishing ESS from ULMS and LG ESS from 'LG' ULMS. Finally, stathmin1 expression could be of value in differentiating LM from uterine sarcomas.

BRAF V600E in papillary thyroid carcinoma is associated with increased programmed death ligand 1 expression and suppressive immune cell infiltration.

BACKGROUND: There remain a small number of patients with papillary thyroid cancer (PTC) who suffer recurrence, metastases, or death. While mutation of the BRAF gene, corresponding to the constitutively active BRAF(V600E) protein, has been associated with worse clinical outcomes in thyroid cancer, the reasons underlying this observation are presently unknown. Disruption of endogenous host immune surveillance and promotion of tumor immune escape is one mechanism by which BRAF(V600E) tumors may achieve more aggressive behavior. This study evaluated the relationship between BRAF(V600E) status and known strategies of tumor-mediated immune suppression. METHODS: Tissue sections of PTC tumors from 33 patients were evaluated by immunohistochemistry for tumor-expressed suppressive ligands and enzymes and effector and suppressor populations of tumor-infiltrating immune cells. Presence of BRAF(V600E) was evaluated by direct DNA sequencing of PTC specimens and the results correlated with tumor-expressed molecules and tumor-infiltrating immune cell populations, as well as patient characteristics and pathologic findings. RESULTS: BRAF(V600E) tumors more often express high levels of immunosuppressive ligands programmed death ligand 1 (53% vs. 12.5%) and human leukocyte antigen G (41% vs. 12.5%) compared to BRAF wild-type tumors. There was no association between indoleamine 2,3-dioxygenase 1 expression and BRAF(V600E) status. Furthermore, BRAF(V600E) tumors demonstrate both lower CD8(+) effector to FoxP3(+) regulatory T cell, and CD68(+) pan-macrophage to CD163(+) M2 macrophage ratios, indicating relative increases in suppressive T cell and macrophage components, respectively. CONCLUSIONS: Overall, BRAF(V600E) PTC tumors display a broadly immunosuppressive profile and evidence of disturbed host tumor immune surveillance that may contribute to the poorer outcomes observed in this subset of patients with thyroid cancer.

Effects of the change in cutoff values for human epidermal growth factor receptor 2 status by immunohistochemistry and fluorescence in situ hybridization: a study comparing conventional brightfield microscopy, image analysis-assisted microscopy, and interobserver variation.

CONTEXT: New guidelines for HER2 testing have been introduced. OBJECTIVES: To evaluate the difference in HER2 assessment after introduction of new cutoff levels for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and to compare interobserver agreement and time to score between image analysis and conventional microscopy. DESIGN: Samples from 150 patients with breast cancer were scored by 7 pathologists using conventional microscopy, with a cutoff of both 10% and 30% IHC-stained cells, and using automated microscopy with image analysis. The IHC results were compared individually and to HER2 status as determined by FISH, using both the approved cutoff of 2.0 and the recently introduced cutoff of 2.2. RESULTS: High concordance was found in IHC scoring among the 7 pathologists. The 30% cutoff led to slightly fewer positive IHC observations. Introduction of a FISH equivocal zone affected 4% of the FISH scores. If cutoff for FISH is kept at 2.0, no difference in patient selection is found between the 10% and the 30% IHC cutoff. Among the 150 breast cancer samples, the new 30% IHC and 2.2 FISH cutoff levels resulted in one case without a firm diagnosis because both IHC and FISH were equivocal. Automated microscopy and image analysis-assisted IHC led to significantly better interobserver agreement among the 7 pathologists, with an increase in mean scoring time of only about 30 seconds per slide. CONCLUSIONS: The change in cutoff levels led to a higher concordance between IHC and FISH, but fewer samples were classified as HER2 positive.

USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics.

Head and neck squamous cell carcinomas (HNSCC) are common and aggressive tumors that have not seen an improvement in survival rates in decades. These tumors are believed to evade the immune system through a variety of mechanisms and are therefore highly immune modulatory. In order to elucidate their interaction with the immune system and develop new therapies targeting immune escape, new pre-clinical models are needed. A novel human cell line, USC-HN2, was established from a patient biopsy specimen of invasive, recurrent buccal HNSCC and characterized by morphology, heterotransplantation, cytogenetics, phenotype, gene expression, and immune modulation studies and compared to a similar HNSCC cell line; SCCL-MT1. Characterization studies confirmed the HNSCC origin of USC-HN2 and demonstrated a phenotype similar to the original tumor and typical of aggressive oral cavity HNSCC (EGFR(+)CD44v6(+)FABP5(+)Keratin(+) and HPV(-)). Gene and protein expression studies revealed USC-HN2 to have highly immune-modulatory cytokine production (IL-1ß, IL-6, IL-8, GM-CSF, and VEGF) and strong regulatory T and myeloid derived suppressor cell (MDSC) induction capacity in vitro. Of note, both USC-HN2 and SCCL-MT1 were found to have a more robust cytokine profile and MDSC induction capacity when compared to seven previously established HNSCC cell lines. Additionally, microarray gene expression profiling of both cell lines demonstrate up-regulation of antigen presenting genes. Because USC-HN2 is therefore highly immunogenic, it also induces strong immune suppression to evade immunologic destruction. Based upon these results, both cell lines provide an excellent model for the development of new suppressor cell-targeted immunotherapies.

Establishment and characterization of a novel head and neck squamous cell carcinoma cell line USC-HN1.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal malignancy. Publically available cell lines are mostly of lingual origin, or have not been carefully characterized. Detailed characterization of novel HNSCC cell lines is needed in order to provide researchers a concrete keystone on which to build their investigations. METHODS: The USC-HN1 cell line was established from a primary maxillary HNSCC biopsy explant in tissue culture. The immortalized cells were then further characterized by heterotransplantation in Nude mice; immunohistochemical staining for relevant HNSCC biomarkers; flow cytometry for surface markers; cytogenetic karyotypic analysis; human papillomavirus and Epstein-Barr virus screening; qRT-PCR for oncogene and cytokine analysis; investigation of activated, cleaved Notch1 levels; and detailed 35,000 gene microarray analysis. RESULTS: Characterization experiments confirmed the human HNSCC origin of USC-HN1, including a phenotype similar to the original tumor. Viral screening revealed no HPV or EBV infection, while western blotting displayed significant upregulation of activated, cleaved Notch1. CONCLUSIONS: USC-HN1, a novel immortalized cell line has been derived from a maxillary HNSCC. Characterization studies have shown that the cell line is of HNSCC origin and displays many of the same markers previously reported in the literature. USC-HN1 is available for public research and will further the investigation of HNSCC and the development of new therapeutic modalities.

Gallstone-induced inflammatory fibrosis: a relentless clinical course of retained gallstones after laparoscopic cholecystectomy.

Multiple reports in the literature confirm that retained gallstones spilled during laparoscopic cholecystectomy perpetuate chronic inflammation and suppuration long after the initial operation. Two patients who had previously undergone laparoscopic cholecystectomy presented to our institution with complications of retained stones. Patient 1 presented with right upper quadrant pain and a mass involving the right hepatic lobe. Patient 2 presented with a draining right flank abscess. Both underwent exploratory laparotomy at which time multiple abscess cavities were found, many of which contained retained gallstones. Patient 1 required reoperation for recurrent abscesses 7 months after the initial procedure and has been disease free for 6 months. Patient 2 had abscess recurrence that required percutaneous drainage 1 year after the original procedure and has not had recurrence for 4 years.

Microstructured optical fibers as high-pressure microfluidic reactors.

Deposition of semiconductors and metals from chemical precursors onto planar substrates is a well-developed science and technology for microelectronics. Optical fibers are an established platform for both communications technology and fundamental research in photonics. Here, we describe a hybrid technology that integrates key aspects of both engineering disciplines, demonstrating the fabrication of tubes, solid nanowires, coaxial heterojunctions, and longitudinally patterned structures composed of metals, single-crystal semiconductors, and polycrystalline elemental or compound semiconductors within microstructured silica optical fibers. Because the optical fibers are constructed and the functional materials are chemically deposited in distinct and independent steps, the full design flexibilities of both platforms can now be exploited simultaneously for fiber-integrated optoelectronic materials and devices.

Surgical clips: a nidus for foreign body reaction after hepatic resection.

This case report describes a patient who underwent segment IV hepatic resection and 7 months later developed an abdominal wall abscess. This was a foreign body reaction to the surgical clips. The patient required an exploratory laparotomy with debridement and excision of the inflammatory mass in the anterior abdominal wall. Although occurrence is rare, foreign body reactions to surgical clips have been reported, especially as a complication of laparoscopic surgery.

Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a widely expressed adhesion molecule in epithelial cancers. The purpose of this study is to determine the protein expression patterns of EpCAM in renal cell carcinoma (RCC) using tissue arrays linked to a clinicopathological database to evaluate both its predictive power in patient stratification and its suitability as a potential target for immunotherapeutic treatment strategies. EXPERIMENTAL DESIGN: The University of California, Los Angeles kidney cancer tissue microarray contains specimens from 417 patients treated with nephrectomy. EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry. The resultant expression reactivity was correlated with clinicopathological variables. RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium. Clear cell RCCs show minimal and infrequent EpCAM expression, whereas chromophobe and collecting duct RCCs both demonstrate intense and frequent expression. Of 318 clear cell carcinomas used in the analysis, 10% were EpCAM positive in > or = 50% of cells, and 8% of patients would be considered candidates for EpCAM-based therapy, based on high expression [> or = moderate intensity and frequent (> or = 50%) expression] and the need for systemic treatment. EpCAM expression was an independent prognostic factor for improved disease-specific survival, with a multivariate hazard ratio of 0.63 (P = 0.017; 95% confidence interval, 0.43-0.92). CONCLUSIONS: EpCAM is a novel prognostic molecular marker in RCC patients, and its positive expression is an independent predictor associated with improved survival. However, high expression in morphologically normal renal tissues and minimal or absent expression in clear cell carcinomas will likely limit the utility of this epithelial marker in targeted treatments of this most common RCC type.