Current trends in medical management of infantile hemangioma.

PURPOSE OF REVIEW: Infantile hemangiomas are the most common benign, soft-tissue tumors of infancy, affecting between 5 and 10% of newborns, and up to 30% of premature infants. Morbidity may include disfigurement and scarring, difficulty in feeding, ulceration, vision loss, airway compromise, congestive heart failure, and death. Advances in understanding the pathogenesis of infantile hemangiomas have given rise to a number of promising treatments. This article reviews the current options for medical management of infantile hemangiomas. RECENT FINDINGS: In the proliferative phase of infantile hemangiomas, vascular endothelial growth factor and basic fibroblast growth factor have shown increased expression, and vascular endothelial growth factor expression has been up-regulated by adrenergic stimulation. Moreover, the role of the renin-angiotensin system in the pathogenesis of infantile hemangiomas has been demonstrated. Numerous medical options have been under investigation. Since 2008, propanolol has become the first-line therapy, whereas other medical treatments are used less frequently or when propanolol is unsuccessful. SUMMARY: Propranolol has been recently adopted as the first-line medical treatment for complicated infantile hemangiomas. Although emerging treatment options and modalities have shown promising results, there need to be high-quality multicenter randomized trials to support these preliminary data.

Clinical characteristics of pediatric granular myringitis.

OBJECTIVE: To determine the clinical characteristics of children with granular myringitis. STUDY DESIGN: Case series with chart review of children with granular myringitis. SETTING: Tertiary care children's hospitals in Delaware and Florida. SUBJECTS AND METHODS: From July 1, 2006, to June 30, 2011, 15 patients were identified with granular myringitis based on International Classification of Diseases, Ninth Revision code 384.1 (10 male, 5 female; 10 left-sided, 5 right-sided). RESULTS: Average age at onset was 10 years (range, 4-18 years). Average length of symptoms was 21 months (range, 3-48 months). Thirteen of the 15 patients (87%) had myringotomy tube placement prior to diagnosis of myringitis, and 11 had a previous perforation (73%). Eleven myringoplasties were performed on 8 (53%) patients prior to the onset of granular myringitis (5 fascia, 2 fat, 2 cartilage, 1 paper patch, and 1 at an outside hospital that was unknown). A total of 27 otolaryngologic surgical procedures were done on 14 of 15 patients. Ten patients (67%) had audiometry performed, and 6 (40%) had ear cultures. Medical treatment included ciprofloxacin and dexamethasone otic drops in all patients, oral antibiotics in 4 patients, and additional topical agents in 8 patients. Two patients had laser resurfacing, and 1 patient had surgical curettage. Five patients had long-term remission, 8 had intermittent remission, and 2 had no remission of their symptoms. CONCLUSION: Granular myringitis is a chronic, recalcitrant disease typically preceded by myringotomy and tube placement or myringoplasty/tympanoplasty. Medical and surgical intervention is varied and often does not lead to permanent resolution of the disease.

Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.

Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67-/TOMM20-/COX-/MCT1-); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67-/TOMM20-/COX-/MCT1-). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67-/MCT4+) within the tumor can actually determine clinical outcome, likely by providing high-energy mitochondrial "fuels" for proliferative cancer cells to burn. Finally, we also show that in normal mucosal tissue, the basal epithelial "stem cell" layer is hyper-proliferative (Ki-67+), mitochondrial-rich (TOMM20+/COX+) and is metabolically programmed to use mitochondrial fuels (MCT1+), such as ketone bodies and L-lactate. Thus, oxidative mitochondrial metabolism (OXPHOS) is a common feature of both (1) normal stem cells and (2) proliferating cancer cells. As such, we should consider metabolically treating cancer patients with mitochondrial inhibitors (such as Metformin), and/or with a combination of MCT1 and MCT4 inhibitors, to target "metabolic symbiosis."

Atypical presentation of geniculate ganglion venous malformation in a child: conductive hearing loss without facial weakness.

We describe an unusual presentation of geniculate ganglion venous malformation, a rare facial nerve lesion, emphasizing the importance of the differential diagnosis, imaging characteristics, and controversies in management. A child presented with moderate right-sided conductive hearing loss and a House-Brackmann grade I facial nerve function bilaterally. Computed tomography and magnetic resonance imaging showed a mass demonstrating features consistent with a geniculate ganglion venous malformation. To our knowledge, this is the first pediatric case of geniculate ganglion venous malformation presenting solely with conductive hearing loss. Proper management requires differentiating this condition from other geniculate and temporal bone lesions.

Outcomes after the use of gastrostomy tubes in patients whose head and neck cancer was managed with radiation therapy.

BACKGROUND: The purpose of this study was to examine the effect of continued oral intake and duration of gastrostomy tube placement on posttreatment nutritional outcomes in patients being irradiated for head and neck cancer. METHODS: Factors associated with continued oral intake and its association with posttreatment outcomes were analyzed. RESULTS: Patients with no oral intake (39.6% of 91) were more likely to have laryngeal tumors, advanced disease, and pretreatment gastrostomy tube placement. Of the 55 patients whose gastrostomy tubes had been removed, those with continued oral intake and shorter gastrostomy tube placement were more likely to maintain their weight and report eating scores in the higher-functioning category, but have more restricted diets. Observed survival was significantly better for the continued-oral-intake group (p = .001). CONCLUSION: The beneficial effects of continued oral intake and shorter gastrostomy tube placement on posttreatment outcomes shown in this study suggest that clinicians involved in these patients' care should emphasize oral intake during treatment.