Technique for histological control of surgical margins in lip cancer.

To preserve oral function and achieve acceptable cosmetic results, intraoperative control of surgical margins with frozen section evaluation may help to determine surgical technique in lip cancer. However, frozen section analysis is usually limited to suspicious areas and has not been systematically performed among surgeons. The accuracy of such analysis for detecting histological surgical margins is highly dependent on the methods used to obtain and analyze the margins. Improving the pathodiagnostic reliability of conventional intraoperative frozen section evaluation is the most important goal of surgical management in our method. We describe the successful use of the "double-blade method" in lip cancer treatment. The technique we describe has the advantage of histologically confirming clear margins in lip cancer. This method appears to be time-saving and easy to apply with existing surgical systems. In addition, this method may be used as an alternative to complete evaluation of lateral surgical margins that is important in planning a suitable surgical reconstruction procedure in lip cancer at many institutions where Mohs micrographic surgery is difficult to perform.

Establishment of a novel experimental model of human angiosarcoma and a VEGF-targeting therapeutic experiment.

BACKGROUND: Angiosarcoma is one of the most life-threatening neoplasms with strong resistance to conventional chemotherapy/radiotherapy; consequently, alternative therapeutic agents are urgently required. One factor in delaying the therapy development is the limitation of experimental models. OBJECTIVE: We established a novel experimental angiosarcoma model. METHODS: From surgically resected tissue, human AS cell line was established. Using xenograft of AS cell line, we performed therapeutic experiments with the anti-human VEGF Ab or the receptor tyrosine kinase inhibitor. RESULTS: First we generated an angiosarcoma cell line, HAMON (human angiosarcoma, monoclonal), which expresses CD31 and produces tumors in immunodeficient mice. HAMON expresses VEGFR2 and that exogenous VEGF leads to HAMON proliferation in vitro. Anti-human VEGF Ab bevacizumab treatment failed to suppress HAMON proliferation in vitro and in vivo. Furthermore, the receptor tyrosine kinase inhibitor sunitinib did not suppress HAMON proliferation in vitro. Similarly, in in vivo therapeutic experiments, even high doses of sunitinib failed to inhibit tumor growth. Finally, we checked whether compensatory activation of VEGF signaling occurred after sunitinib addition. VEGF protein secretion, VEGF mRNA synthesis and VEGFR2 phosphorylation all were unaffected in HAMON after sunitinib treatment. CONCLUSION: A novel in vitro and in vivo experimental model of human angiosarcoma has been successfully established. With this model, we were able to perform therapeutic experiments. In addition, our angiosarcoma cell line, HAMON, is quite useful for identifying key molecules in angiosarcoma.

c-MYC-induced sebaceous gland differentiation is controlled by an androgen receptor/p53 axis.

Although the sebaceous gland (SG) plays an important role in skin function, the mechanisms regulating SG differentiation and carcinoma formation are poorly understood. We previously reported that c-MYC overexpression stimulates SG differentiation. We now demonstrate roles for the androgen receptor (AR) and p53. MYC-induced SG differentiation was reduced in mice lacking a functional AR. High levels of MYC triggered a p53-dependent DNA damage response, leading to accumulation of proliferative SG progenitors and inhibition of AR signaling. Conversely, testosterone treatment or p53 deletion activated AR signaling and restored MYC-induced differentiation. Poorly differentiated human sebaceous carcinomas exhibited high p53 and low AR expression. Thus, the consequences of overactivating MYC in the SG depend on whether AR or p53 is activated, as they form a regulatory axis controlling proliferation and differentiation.

Linear congenital molluscum contagiosum on the coccygeal region.

Congenital molluscum contagiosum is rare but has been reported previously. We present a unique case of linear congenital molluscum on the coccygeal region. To make a correct diagnosis, avoid unnecessary examination, and start appropriate treatment as soon as possible, it is beneficial for dermatologists to be aware that molluscum contagiosum can present at birth and can be linear.

Sequential local injection of low-dose interferon-beta for maintenance therapy in stage II and III melanoma: a single-institution matched case-control study.

OBJECTIVE: To determine the beneficial effect of maintenance therapy in stage II and III melanoma by sequential local injection of low-dose interferon-ß. METHODS: We reviewed 46 patients with stage II and III primary melanoma at our institution from 2004 through 2009. Twenty-one patients were treated with interferon-ß maintenance therapy consisting of subcutaneous injection of natural interferon-ß at a dose of 3 × 10(6) IU/day for 10 consecutive days, and 25 patients underwent observation alone. RESULTS: Compared with all patients, overall survival and relapse-free survival were significantly worse in the observation group than in the interferon-ß group (p = 0.024 and 0.029, respectively). In stage II, a significant difference in overall survival, but not in relapse-free survival, was seen between the two groups (p = 0.041). When the interferon-ß group was stratified by subgroup, there was a statistical difference only between dosage and duration (p = 0.027 and p < 0.001, respectively). CONCLUSIONS: This study demonstrates that maintenance therapy by interferon-ß is beneficial in the outcome of the disease without substantial toxic effects, especially in patients with stage II melanoma. Extension of the duration of treatment beyond 2 years could further improve the therapeutic efficacy of interferon-ß.

Spontaneous remission of solitary-type infantile myofibromatosis.

Infantile myofibromatosis is a rare fibrous tumor of infancy. The cutaneous solitary type has typically an excellent prognosis. However, histologically, it is important to rule out leiomyosarcoma, which has a poor prognosis. The low frequency of mitosis was definitive for a diagnosis of infantile myofibromatosis. We present a cutaneous solitary-type case of infantile myofibromatosis. Following incisional biopsy, the tumor remitted spontaneously.

Response of intractable skin ulcers in recessive dystrophic epidermolysis bullosa patients to an allogeneic cultured dermal substitute.

Recessive dystrophic epidermolysis bullosa (RDEB) is an inherited skin disorder caused by mutations in the COL7A1 gene, which encodes collagen VII (COL7). Skin ulcers in RDEB patients are sometimes slow to heal. We describe here the therapeutic response of intractable skin ulcers in two patients with generalized RDEB to treatment with an allogeneic cultured dermal substitute (CDS). Skin ulcers in both patients epithelialized by 3-4 weeks after this treatment. Immunohistochemical studies demonstrated that the COL7 expression level remained reduced with respect to the control skin and that it did not differ significantly between graft-treated and untreated areas. Electron microscopy showed aberrant anchoring fibrils beneath the lamina densa of both specimens. In conclusion, CDS is a promising modality for treatment of intractable skin ulcers in patients with RDEB, even though it does not appear to increase COL7 expression.

Controlling the histological margin for non-melanoma skin cancer conveniently using a double-bladed scalpel.

BACKGROUND: In some countries, intraoperative histological evaluation to control the surgical margin for non-melanoma skin cancer is widely used instead of Mohs micrographic surgery. Nevertheless, this evaluation by frozen section analysis is usually limited to suspicious areas. OBJECTIVES: To evaluate the efficacy of double-bladed scalpel for intraoperative histological margin control for non-melanoma skin cancers. METHODS: Between 2005 and 2009, 10 basal cell carcinomas and 5 squamous cell carcinomas were underwent complete histological margin control in which a double-bladed scalpel was used during the surgery at the Hokkaido University Hospital in Japan. RESULTS: The mean number of re-excisions required for complete tumor resection was 1.4 times. Nine (60%) of the 15 patients obtained histological clearance of all surgical margins at the first re-excision. The mean size of total surgical margin was 6.1 mm (range: 2-12 mm). The median time from the first tumor excision to reconstruction was 124 min. No local recurrences have been reported. CONCLUSIONS: This method may be used as an alternative for complete histological margin control at many hospitals where it is difficult to perform Mohs micrographic surgery.