Osteosarcoma of the Head and Neck: Meta-analysis of Nonrandomized Studies

To assess the role of adjuvant therapy in the treatment of osteogenic sarcoma of the head and neck, treatment and survival information from 173 patients with osteosarcoma of the head and neck was entered into a database. A meta-analysis of the data was attempted with primary emphasis on the effect of adjuvant therapy on disease outcome. The overall 5-year survival was 37%. Patients with mandibular and maxillary tumors had similar survival rates; both groups fared significantly better than patients with extragnathic tumors (P<0.001). Treatment with surgery alone was associated with significantly longer survival rates (P<0.03) than surgery with adjuvant therapy. In the majority of patients reported, information about surgical margins was not available. For this reason, the differences may not adequately represent the effect of adjuvant therapy. While there have been encouraging results with adjuvant treatment protocols for long bone osteosarcoma, the ultimate role of radiation and chemotherapy in the management of osteosarcoma of the head and neck remains unproven. Nevertheless, we recommend that adjuvant therapy be considered due to the poor prognosis in osteosarcoma of the head and neck.     

Mosaicism for Dominant Collagen 6 Mutations as a Cause for Intrafamilial Phenotypic Variability

Collagen 6‐related dystrophies and myopathies (COL6‐RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter‐ and intrafamilial variable expressivity are commonly observed. We present clinical, immunohistochemical, and genetic data on four COL6‐RD families with marked intergenerational phenotypic heterogeneity. This variable expression seemingly masquerades as anticipation is due to parental mosaicism for a dominant mutation, with subsequent full inheritance and penetrance of the mutation in the heterozygous offspring. We also present an additional fifth simplex patient identified as a mosaic carrier. Parental mosaicism was confirmed in the four families through quantitative analysis of the ratio of mutant versus wild‐type allele (COL6A1, COL6A2, and COL6A3) in genomic DNA from various tissues, including blood, dermal fibroblasts, and saliva. Consistent with somatic mosaicism, parental samples had lower ratios of mutant versus wild‐type allele compared with the fully heterozygote offspring. However, there was notable variability of the mutant allele levels between tissues tested, ranging from 16% (saliva) to 43% (fibroblasts) in one mosaic father. This is the first report demonstrating mosaicism as a cause of intrafamilial/intergenerational variability of COL6‐RD, and suggests that sporadic and parental mosaicism may be more common than previously suspected.     

Position of Glycine Substitutions in the Triple Helix of COL6A1, COL6A2, and COL6A3 is Correlated with Severity and Mode of Inheritance in Collagen VI Myopathies

Glycine substitutions in the conserved Gly‐X‐Y motif in the triple helical (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate (INT) phenotypes. We describe clinical and genetic characteristics of 97 individuals with glycine substitutions in the TH domain of COL6A1, COL6A2, or COL6A3 and add a review of 97 published cases, for a total of 194 cases. Clinical findings include severe, INT, and mild phenotypes even from patients with identical mutations. INT phenotypes were most common, accounting for almost half of patients, emphasizing the importance of INT phenotypes to the overall phenotypic spectrum. Glycine substitutions in the TH domain are heavily clustered in a short segment N‐terminal to the 17th Gly‐X‐Y triplet, where they are acting as dominants. The most severe cases are clustered in an even smaller region including Gly‐X‐Y triplets 10–15, accounting for only 5% of the TH domain. Our findings suggest that clustering of glycine substitutions in the N‐terminal region of collagen VI is not based on features of the primary sequence. We hypothesize that this region may represent a functional domain within the triple helix.     

Angiosarcoma of the of scalp with calvarium involvement in a 50-year-old African-American man

BACKGROUND: Angiosarcoma of the scalp is a rare, aggressive, and deadly cancer that affects mainly elderly Caucasian men. OBJECTIVES: The insidious and masquerading presentation of angiosarcoma poses enormous diagnostic challenges for primary care providers. PATIENTS/METHODS: We present a case of a 50-year-old black man referred for evaluation of a 3.7-cm-x-5.4-cm ulcerated, fluctuant scalp lesion that had failed to respond to different antibiotics and proper wound care. RESULTS: Surgical excision and subsequent histopathology revealed angiosarcoma. CONCLUSIONS: This case report highlights the importance of high index of suspicion for early diagnosis of cancerous lesions in wounds and stresses the need to include angiosarcoma in the differential diagnosis for all face and scalp lesions, as early detection may save lives. A comprehensive literature review is also presented.     

Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes

Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration. In bradycardic (atrioventricular-blocked) hearts, eight simultaneously recorded epi- and endocardial MAPs demonstrated increased dispersion of repolarization in the presence of all three antibiotics. Erythromycin and clarithromycin led to early afterdepolarizations (EADs) and torsade de pointes (TdP) after lowering of potassium concentration. In the presence of azithromycin, no EAD or TdP occurred. Erythromycin and clarithromycin changed the MAP configuration to a triangular pattern, whereas azithromycin caused a rectangular pattern of MAP prolongation. In 13 additional hearts, 150 microM azithromycin was administered after previous treatment with 300 microM erythromycin and suppressed TdP provoked by erythromycin. In conclusion, macrolide antibiotics lead to similar prolongation of repolarization but show a different proarrhythmic potential (erythromycin > clarithromycin > azithromycin). In the presence of azithromycin, neither EAD nor TdP occur. This effect may be related to a rectangular pattern of action potential prolongation, whereas erythromycin and clarithromycin cause triangular action potential prolongation and induce TdP.     

Serum Circ‐FAF1/Circ‐ELP3: A novel potential biomarker for breast cancer diagnosis

BackgroundRecently, measurement of serum circular RNAs (circRNAs) as a non‐invasive tumor marker has been considered more. We designed the present study to investigate the diagnostic efficiency of serum Circ‐ELP3 and Circ‐FAF1, separately and simultaneously, for diagnosis of patients with breast cancer.MethodsSeventy‐eight female patients diagnosed as primary breast cancer participated in this study. We measured the level of circRNAs in serum specimens of the studied subjects. A receiver operating characteristic (ROC) curve was plotted and the diagnostic efficiency for both circRNAs was determined.ResultsCompared to non‐cancerous controls, Circ‐ELP3 was upregulated in breast cancer patients (p‐value = 0.004). On the other hand, serum Circ‐FAF1 was seen to be decreased in breast cancer patients than controls (p‐value = 0.001). According to ROC curve results, the area under the curve (AUC) for Circ‐ELP3 and Circ‐FAF1 was 0.733 and 0.787, respectively. Furthermore, the calculated sensitivity and specificity for Circ‐ELP3 and Circ‐FAF1 were 65, 64% and 77, 74%, respectively. Merging both circRNAs increased the diagnostic efficiency, with a better AUC, sensitivity and specificity values of 0.891, 96 and 62%, respectively.ConclusionBriefly, our results revealed the high diagnostic value for combined circRNAs panel, including Circ‐ELP3 and Circ‐FAF1 as a non‐invasive marker, in detection of breast carcinomas.     

Comparison of the safety and efficacy of emboli prevention devices versus platelet glycoprotein IIb/IIIa inhibition during carotid stenting

Distal embolization is the main potential risk of carotid stenting, and techniques to minimize this risk are evolving. Between July 1998 and March 2002, 305 consecutive patients who underwent elective or urgent percutaneous carotid intervention at The Cleveland Clinic were prospectively followed. During this period, the clinical practice of carotid stenting evolved from the routine use of glycoprotein IIb/IIIa inhibitors (GPIs) to routine emboli-prevention device (EPD) placement. A total of 199 patients received adjunctive GPIs (91% abciximab), and 106 patients underwent the procedure with an EPD (85% filter design, 15% occlusive balloon). At 30 days, the composite end point of neurologic death, nonfatal stroke, and major bleeding, including intracranial hemorrhage, was significantly lower among patients treated with EPDs compared with those treated with GPIs (0% vs 5.1%, p = 0.02). EPDs may provide an overall safer and more effective means of neuroprotection during carotid stenting than GPIs.     

Management of malar folds in blepharoplasty

Objectives/Hypothesis: To define the anatomy and location of malar folds as distinguished from lower eyelid skin and orbital fat and to teach a new surgical technique for the management of the aging eye. Study Design: Retrospective report of a surgical procedure designed to address the malar folds. Methods: Analysis of preoperative and postoperative photographic documentation for surgical planning and long-term result. Results: Patient satisfaction and lack of recurrence, without the requirement of direct excision, were noted in all patients studied. Conclusion: This presentation describes a new simple technique for the management of the folds and cutaneous and subcutaneous prominences that occur inferior to the lower eyelid skin. The operation addresses the correction by a combination of skin/muscle flap lower eyelid blepharoplasty with immediately subcutaneous (skin flap) elevations over the carefully delineated malar prominences; the removal of the deep fat that may or may not be associated with dehiscence of fat through the thin inferior fibers of the orbicularis muscle; and finally suspension of the remaining subcutaneous tissue and the muscle to the periosteum of the inferior orbital rim as well as suspension of the orbicularis muscle margin to the lateral orbital periosteum or the lateral canthal ligament area. The technique is designed to manage the more commonly found malar prominences but can be applied in the management of more pronounced festoons involving skin, muscle, and fat. Laryngoscope, 108:1659–1663, 1998     

Fibrous dysplasia of a third toe

Fibrous dysplasia is a benign disorder of bone, consisting of one or more foci of fibro osseous tissue within the matrix of the affected bone. Fibrous dysplasia usually effects the femur, tibia, ribs, and facial bones and is rarely seen in feet. An unusual case of fibrous dysplasia involving the third toe is presented.