Transdermal drug targeting and functional imaging of tumor blood vessels in the mouse auricle.

Subcutaneously growing tumors are widely utilized to study tumor angiogenesis and the efficacy of antiangiogenic therapies in mice. To additionally assess functional and morphologic alterations of the vasculature in the periphery of a growing tumor, we exploited the easily accessible and hierarchically organized vasculature of the mouse auricle. By site-specific subcutaneous implantation of a defined preformed mouse B16/F0 melanoma aggregate, a solid tumor nodule developed within 14 d. Growth of the tumor nodule was accompanied by a 4-fold increase in its perfusion as well as a 2- to 4-fold elevated diameter and perfusion of peripheral blood vessels that had connected to the tumor capillary microvasculature. By transdermal application of the anticancer drug bortezomib, tumor growth was significantly diminished by about 50% without provoking side effects. Moreover, perfusion and tumor microvessel diameter as well as growth and perfusion of arterial or venous blood vessels supplying or draining the tumor microvasculature were decreased under these conditions by up to 80%. Collectively, we observed that the progressive tumor growth is accompanied by the enlargement of supplying and draining extratumoral blood vessels. This process was effectively suppressed by bortezomib, thereby restricting the perfusion capacity of both extra and intratumoral blood vessels.

Induction Hedgehog pathway inhibition followed by combined-modality radiotherapy for basal cell carcinoma.

Basal cell carcinoma (BCC), the most common cancer in the U.S.A., is treated primarily with local excision. In some cases, lesion size, location or extent prevent complete resection. Locally advanced BCC responds to systemic therapy with the Hedgehog pathway inhibitor vismodegib, but withdrawal of treatment may result in disease relapse. Here we present a case of locally advanced auricular BCC treated with induction vismodegib and radiation, resulting in durable local control and an acceptable level of acute toxicity.

External auditory canal and middle ear relapse of acute promyelocytic leukemia treated with arsenic trioxide: case report and review of the literature.

Extramedullary involvement occurs infrequently in acute promyelocytic leukemia and is said to be more common after treatment with all-trans retinoic acid. We describe a 9-year-old girl who had an isolated external auditory canal and middle ear relapse after treatment with all-trans retinoic acid and chemotherapy. A patient with cytogenetically and molecularly confirmed acute promyelocytic leukemia developed isolated extramedullary relapse in the auditory canal and middle ear 4 years and 9 months after initial diagnosis, while in hematologic and molecular remission, successfully treated with arsenic trioxide alone.

Electroporation therapy of skin cancer in the head and neck area.

BACKGROUND: Electroporation therapy is a new cancer treatment modality in which a locally applied electrical field enhances cell membrane permeability, allowing greater intracellular accumulation of a chemotherapeutic agent. OBJECTIVE: To evaluate the efficacy of electroporation therapy in treating basal cell and squamous cell carcinomas of the skin. MATERIALS AND METHODS: Six patients with skin cancer of the head and neck were treated using electroporation therapy with intratumorally injected bleomycin. Orbital growth, facial nerve proximity, or proximity to cartilage of the external meatus complicated four of these tumors. The intention was curative. The follow-up period was 24 months and included biopsies after 8 weeks. RESULTS: In four of the six patients, one treatment was enough to eradicate the tumor. In one patient, the tumor persisted even after a second treatment with electroporation therapy. A septal cartilage perforation was the only major complication. The cosmetic results were very satisfactory. One additional recurrence was recorded 6 months after the follow-up period CONCLUSION: Electroporation therapy is a promising new cancer treatment that should be further evaluated as an alternative to surgery, especially in complicated skin cancer.

Clinical response to pazopanib in a patient with endolymphatic sac tumor not associated with von Hippel-Lindau syndrome.

Endolymphatic sac tumors (ELSTs) are rare, locally invasive, vascular tumors of the temporal bone. These lesions are associated with von Hippel-Lindau syndrome but may arise sporadically. Early surgical intervention is recommended to prevent permanent neurologic deficits; however, many ELSTs are unresectable or are subtotally resected due to neurovascular compromise. Chemotherapeutic salvage therapy in trials of neoplasms of associated syndromes has targeted angiogenesis with variable response. We present the case of a sporadic ELST, previously minimally responsive to bevacizumab, treated with pazopanib, a multi-kinase inhibitor and antiangiogenic, with good response. Cases such as our patient may demonstrate the utility of novel antiangiogenics in the treatment of these rare neoplasms, particularly when the tumor is unresectable or necessitates subtotal resection.

Complete response with talimogene laherparepvec in recurrent melanoma of the ear: A case report.

The current standard of care for cutaneous melanoma of the ear is surgical excision. This approach may result in unfavorable functional and cosmetic outcomes. We report here a case of recurrent melanoma of the ear that achieved complete response with talimogene laherparepvec treatment after the patient declined surgical resection.

Superselective, intra-arterial, rapid infusion chemotherapy for external auditory canal carcinoma.

Previously, the treatment of carcinoma of the external auditory canal has mainly involved surgical resection. In order to enable organ preservation and to obtain cancer-free surgical margins, we introduced the use of superselective, intra-arterial, rapid infusion chemotherapy combined with radiotherapy to treat this condition.We reviewed our patients' tumour stages, feeding arteries and clinical outcomes. Tumours were staged according to the Pittsburgh staging system. Chemotherapy was administered intra-arterially in the angiography suite via transfemoral catheterisation of the feeding arteries. Four patients underwent superselective, intra-arterial, rapid infusion chemo-radiotherapy. A complete response was obtained in all four patients. The overall toxic side effects were modest.Superselective, intra-arterial, rapid infusion chemotherapy can be an effective, organ-preserving treatment for external auditory canal carcinoma, with a high cure rate.

Unusual presentation for small lymphocytic lymphoma: Case report of a man with bilateral ear involvement and review of the literature.

INTRODUCTION: Ear involvement by non-Hodgkin lymphoma is quite rare and can be mistaken for other common lesions encountered in otolaryngology. The literature on this subject is also limited. CASE SUMMARY: A 45-year-old man with bilateral ear nodules that progressed over two years. Biopsy of the right ear revealed a B-cell small lymphocytic lymphoma (SLL). The patient responded to radiotherapy well. He received an additional dose two months after the initial treatment because of a remaining nodularity on the right earlobe. After several months, he presented a new lesion on his nasal tip, for which a biopsy confirmed a lymphoma relapse. The patient was managed with oral prednisone and low-dose radiation with a favourable response. DISCUSSION: This case highlights the importance of including lymphoma in the differential diagnosis of ear lesions from an otolaryngology perspective. A biopsy of any lesion or nodule with an atypical course should be considered for appropriate diagnosis and management.

CD20-negative primary middle ear diffuse large B-cell lymphoma coexpressing MYC and BCL-2 secondary to acute lymphoblastic leukemia: A case report.

RATIONALE: Second diffuse large B-cell lymphoma (DLBCL) after treatment of acute lymphoblastic leukemia (ALL) is uncommon. To our knowledge, primary middle ear DLBCL which presents CD20-negative and coexpression of MYC and BCL-2 has not been reported yet. PATIENT CONCERNS: A 20-year-old Chinese man complained fever and weakness for 2 months. Subsequently bone marrow morphology and flow cytometry immunophenotype suggested ALL. Administrated with 9 cycles of multiagent combined chemotherapy, he felt right ear progressive hearing loss, otalgia, aural fullness. Otoendoscopic examination revealed a pitchy mass obstructing the right external auditory canal. Then the mass resection was performed for biopsy and immunohistochemistry examination. DIAGNOSIS: The mass was diagnosed as DLBCL which was negative for CD20 and double expression of MYC and BCL-2. INTERVENTIONS: Chemotherapy. OUTCOMES: The patient eventually gave up and died of severe infection. LESSONS: Although intensive chemotherapy has markedly improved the survival of ALL, more and more secondary cancers have been reported. In addition, primary middle ear lymphoma is much rare; hence, it is easy to be misdiagnosed. Furthermore, DLBCL with negative CD20 and double expression of MYC and BCL-2 is aggressive, which is characterized by chemotherapy resistance and inferior survival rates. We discuss this case aiming at raising awareness of tumors secondary to ALL and exploring the appropriate treatment options for the rare DLBCL.

Audiologic and radiographic response of NF2-related vestibular schwannoma to erlotinib therapy.

BACKGROUND: A 48-year-old man presented to a neurologist with complaints of bilateral hearing loss and tinnitus. The patient was a member of a large family affected by neurofibromatosis type 2 and first noted hearing loss 10 years before presentation. INVESTIGATIONS: Medical and neurological examination, MRI scan of the brain and spinal cord, pure-tone audiometry, NU-6 monosyllabic word test with phoneme scoring, City University of New York topic-related sentences test, noise/voice test of minimal auditory capability battery. DIAGNOSIS: Progressive neurofibromatosis-type-2-related vestibular schwannomas. MANAGEMENT: Annual cranial MRI and audiology, surgical resection of right vestibular schwannoma, high-power behind-the-ear hearing aid, erlotinib therapy for progressive left vestibular schwannoma.

Regression of Kaposi's sarcoma lesions following highly active antiretroviral therapy in an HIV-infected patient.

This case report documents that highly active antiretroviral therapy (HAART) can lead to the regression of Kaposi's sarcoma (KS) lesions in the auditory canal of an HIV-infected male from Chennai, India. In resource-limited settings where administering anti-KS chemotherapeutic agents may not be feasible, HAART alone can be an option in HIV-infected individuals with KS.

Interleukin-10 is an essential modulator of mucoid metaplasia in a mouse otitis media model.

OBJECTIVES: Inflammatory cytokines are involved in the development of mucous cell metaplasia and hyperplasia (MCM) in otitis media (OM). However, which cytokines play an essential role in the MCM of OM is not clear at the moment. METHODS: In this study, we hypothesized that interleukin-10 (IL-10) played an indispensable role in the MCM of bacterial OM, and we used IL-10 knockout mice to test this hypothesis. RESULTS: In wild-type mice, both Streptococcus pneumoniae and Haemophilus influenzae triggered the development of MCM in the middle ear mucosa. In IL-10 knockout mice, the number of goblet cells and mucin-producing cells in the middle ear was significantly reduced after bacterial middle ear infection compared with that in wild-type mice. CONCLUSIONS: We conclude that IL-10 plays an essential role in the MCM of bacterial OM. Interleukin-10 is a potential target for the treatment of MCM in OM.

Merkel cell carcinoma: treatment with bleomycin.

Merkel cell carcinoma is the second most deadly form of skin cancer after melanoma, with a mortality rate of as high as 35 percent. It usually occurs as a deep red or purple dome-shaped tumor on sun-exposed skin of elderly people. Transplant recipients or AIDS patients have a higher incidence of this tumor than normal individuals. There is an association of a polyoma virus with this tumor that may explain the increased incidence in immunosuppression. Surgery, followed by radiation therapy is the standard of treatment. Sentinel node dissection is recommended because this tumor metastasizes often. Chemotherapy, such as is used for oat cell carcinoma of the lung, is advised for metastatic disease. However, systemic chemotherapy protocols have not been overly successful. We have treated four cases of stage-I Merkel cell carcinoma with surgery followed by intralesional bleomycin and have followed these cases for up to five years with no evidence of recurrence or metastasis. One case had radiation post operatively but the tumor recurred. Intralesional bleomycin caused complete regression of this tumor with minimal scarring and long term cure. Bleomycin, besides being a potent chemotherapy agent, has direct antiviral effects that may explain why this drug is so effective in treating Merkel cell carcinoma.

The Auricular VX2 Carcinoma Is a Suitable Animal Model for Identifying Biomarkers for HNSCC Therapy Response.

BACKGROUND/AIM: The rabbit auricular VX2 carcinoma is an established animal model for human head and neck squamous cell carcinoma (HNSCC). Previously, we observed that intraperitoneal oxidative (O3/O2) stress induced tumor remission. Our aim was to evaluate candidate genes associated with tumor regression. MATERIALS AND METHODS: For identification of tumor remission-related genes, microarray analysis was performed with subsequent validation by polymerase chain reaction (PCR), in situ hybridization, immunohistochemistry and western blot analysis. RESULTS: Microarray analysis indicated a prominent reduction of epidermal growth factor receptor (Egfr, Erbb1) expression levels in regressing tumors. Quantitative PCR confirmed a significant (p<0.005) down-regulation of Erbb1-3 mRNA in regressing VX2 tumors. Histological localization of Erbb1-3 mRNA transcript and protein indicated reduced Erbb gene expression occurring at the level of individual VX2 tumor cells rather than solely being an effect of tumor shrinkage. This study highlights changes in the Erbb gene signature of regressing VX2 carcinomas as a predictor for therapy response. The VX2 carcinoma animal model, therefore, appears suitable for the identification and evaluation of new diagnostic, prognostic and therapeutic biomarkers prior to their application in patients with HNSCC.

Merkel cell tumour of the external ear. Report of a case.

Merkel cells carcinoma (MCC) is an uncommon skin lesion, considered a malignancy of the neuroendocrine system, which is found mainly in elderly people. Its incidence is highly correlated with sun exposure or immunodeficiency syndromes. MCC is often an aggressive tumour with high tendency for local recurrence, lymph node involvement and distant metastasis. To our best knowledge 20 cases originated from the auricle have been described, 2 of them arising from external ear canal. The authors report a case of the ear canal characterized by two others synchronous tumours and the occurrence of a malignant high grade lymphoma, in which contribute of the pathologist was essential for a critical review. MCC diagnosis is not always easy for its pathological and clinical features and it should always be considered in presence of lymphoma. A multidisciplinary approach is basic.