Antonio P. Cruz

The nuclear factor kappa B (NF-κB): A potential therapeutic target for estrogen receptor negative breast cancers

The effect of a kinase inhibitor Go6796 on growth of epidermal growth factor (EGF)-stimulated estrogen receptor negative (ER−) breast cancer cells in vivo and role of nuclear factor kappa B (NF-κB) on tumorogenesis have been investigated. This was studied in an animal model by implanting ER− mouse mammary epithelial tumor cells (CSMLO) in syngeneic A-J mice. (i) Local administration of Go6976 an inhibitor of protein kinases C alpha and beta inhibited growth of tumors and caused extensive necrotic degeneration and regression of the tumors without causing any microscopically detectable damage to the vital organs liver and lung. (ii) Stable expression of dominant-negative mutants of the beta subunit (dnIkkβ) of the inhibitory kappa B (IκB) kinase (dnIkk) that selectively blocked activation of NF-κB caused loss of tumorigenic potential of CSMLO cells. Stable expression of dnIkkβ also blocked phorbol 12-myristate 13-acetate (PMA)-induced activation of NF-κB and overexpression of cyclin D1, concomitantly with the loss or reduced tumorigenic potential of these cells. Thus, results from in vivo and in vitro experiments strongly suggest the involvement of NF-κB in ER− mammary epithelial cell-mediated tumorigenesis. We propose that blocking NF-κB activation not only inhibits cell proliferation, but also antagonizes the antiapoptotic role of this transcription factor in ER− breast cancer cells. Thus, NF-κB is a potential target for therapy of EGFR family receptor-overexpressing ER− breast cancers.

Treatment of squamous cell carcinoma in situ: a review.

BACKGROUND Squamous cell carcinoma in situ (SCCIS) is thought to be a precursor to squamous cell carcinoma. It should be treated before invasive cancer develops, especially in transplant recipients, who may develop more aggressive skin cancers. Treatment can involve surgical and nonsurgical methods. OBJECTIVE To review the evidence available in the English medical literature for different treatment options of SCCIS on nongenital skin and evaluate the efficacy of each option. METHODS AND MATERIALS A Pubmed search of articles describing the treatment of SCCIS was conducted. Keywords were “treatment,” “Bowens disease,” and “squamous cell carcinoma in situ.” Articles describing the use of surgical excision, curettage and electrodesiccation, cryotherapy, 5‐fluorouracil, imiquimod, radiation, photodynamic therapy, lasers, and rarer methods were reviewed. RESULTS No single treatment can be said to be superior for any one situation. Most studies are small, limiting the power of each. Further studies are needed to clarify optimal treatment protocols for nonsurgical methods such as cryotherapy, photodynamic therapy, and topical chemotherapy. CONCLUSION There are many methods available to treat SCCIS. Physicians should consider each patients situation while keeping in mind that treatment protocols have not been fully defined for most options. The authors have indicated no significant interest with commercial supporters.

Gender differences in tumor and patient characteristics in those undergoing Mohs surgery.

BACKGROUND Nonmelanoma skin cancer is the most common cancer in the United States, and when indicated, Mohs micrographic surgery (MMS) is an effective method for tumor removal. Few studies have focused on gender-specific characteristics among those undergoing MMS. OBJECTIVE To elucidate patient- and tumor-specific characteristics in female MMS patients. MATERIALS AND METHODS We performed a retrospective chart review of 12,344 consecutive patients undergoing MMS from 2005 to 2012. RESULTS There was a 1.5:1 male predominance in the presentation of basal cell carcinoma (BCC) for MMS. However, BCC comprised 72% of tumors in women compared with 63% in men. Presenting tumor sizes of BCCs were smaller in women (0.9 vs 1.2 cm2, p < .01). Superficial BCCs were more common in women (p < .001). Women had fewer squamous cell carcinoma (p < .01) and squamous cell carcinoma in situ (p < .01). They were more likely to present with tumors on their legs and central facial areas, whereas men had more tumors on their scalps and ears. Plastic surgery referral was over twice as common in the female population (p < .01). CONCLUSION In our data set, significant gender-specific differences were found in women compared with men undergoing MMS. These findings may be the result of discrepancies in sun exposure, protective behavior, and cosmetic concern.

Dermabrasion for Actinic Cheilitis

Actinic cheilitis (AC) is a common premalignant condition of the lips resulting from chronic or excessive ultraviolet exposure. Many different treatment modalities have been reviewed in the literature. Current methods include topical 5-fluorouracil, imiquimod, photodynamic therapy, chemical peels, cryosurgery, electrodesiccation and curettage, carbon dioxide laser, and vermilionectomy with or without mucosal advancement.

Paclitaxel-induced neutrophilic adverse reaction and acral erythema.

Paclitaxel, a microtubule-stabilizing anti-neoplastic agent that belongs to the family of taxanes, is used in the treatment of advanced and/or refractory lung, breast, head, neck and other epithelial cancers. Site-specific reactions, such as inflammation at injection sites or cellulitis after extravasation (1), have been reported. Adverse cutaneous reactions associated with paclitaxel treatment include bullous fixed drug eruption (2), erythema multiforme (3), pustular eruption (4), scleroderma-like cutaneous lesions (5), onycholysis (6), and acral erythema (one case) (7). Of note, acral erythema (erythrodysesthesia) has been reported with multi-drug chemotherapy protocols that included paclitaxel (8, 9). We report here the first case of paclitaxel-induced neutrophilic adverse reaction with concomitant acral erythema, and highlight the mechanisms that may be involved.

The Operative Management of Melanoma: Where Does Mohs Surgery Fit In?

BACKGROUND Melanoma is a life‐threatening malignancy. Surgery is the primary management for melanoma, and management guidelines have evolved gradually over a century from radical surgery with lymph node dissection to conservative margin surgery. There are specific rationales and problems with Mohs micrographic (MMS) surgery for managing melanoma. OBJECTIVE To review the literature for the surgical management of melanoma and to understand where MMS fits in this spectrum of management options. CONCLUSIONS MMS should be considered as an option for melanoma surgery, especially when the tumor is found in photodamaged skin. Further randomized prospective clinical trials are needed to select the best therapeutic approach for the treatment of melanoma. Until then, careful margin control is the key for successful tumor removal whether it is standard excision, staged excision, or MMS. The authors have indicated no significant interest with commercial supporters.

Characteristics of basal cell carcinoma of the lip treated using Mohs micrographic surgery.

BACKGROUND There is a lack of U.S‐based studies on basal cell carcinoma (BCC) of the upper lip treated using Mohs micrographic surgery (MMS). OBJECTIVE To explore characteristics of BCC of the upper lip treated using MMS. METHODS We performed a chart review of BCC cases from 2005 to 2011. RESULTS Two hundred eighty‐one cases were identified. There was a slight female predominance (55%). Men had a larger initial (p < .01) and final (p = .03) defect size. Infiltrative tumors had larger initial (p < .01) and final areas (p < .01). Ten percent of tumors were designated recurrent after previous treatment. Recurrent lesions (p < .001) and older age (p = .03) were associated with larger initial size. Complex reconstruction was required: 44% by local flap or graft and 13% by plastic surgery. CONCLUSION There was a 1.2:1 female to male ratio, in contrast to the previously reported female predominance of 3.5:1. This cohort showed a higher recurrence rate than reported in the literature. Men and elderly patients were also found to have significantly larger initial lesion size. Thirteen percent of patients required repair by plastic surgery, reflecting heightened levels of cosmetic concern. These findings suggest that MMS is important in delineating subclinical tumor spread and providing complex repairs.

Characteristics of Squamous Cell Carcinoma In Situ of the Ear Treated Using Mohs Micrographic Surgery

BACKGROUND Mohs micrographic surgery (MMS) is used to treat squamous cell carcinoma in situ (SCCIS) for tissue conservation. OBJECTIVE To examine characteristics of patients with SCCIS of the external ear treated using MMS. METHODS A retrospective review from 2005 to 2011. RESULTS We identified 173 cases of SCCIS of the ear. The population was 94% male (p < .01), with a mean age of 71. Eight percent (n = 13) of tumors were recurrent after prior treatment. Recurrent tumors occurred exclusively in men and were associated with larger initial size (p = .05), more layers for clearance p = .059), and larger final defect size (p = .01). Tumors with larger initial area were independently associated with older age (p < .01). Complexity of repair was independently associated with more layers (p < .01), larger initial area (p = .01), and larger final area (p = .02). Sex did not affect repair type. CONCLUSION SCCIS of the ear predominantly affects men in our referral base of 85% to 90% private patients and 10% to 15% veterans. Recurrent tumors were associated with larger initial size and subclinical spread of tumor. Primary tumors on average required 1.6 layers, validating the utility of MMS in this population in delineating the subclinical spread of SCCIS of the ear.

An Alternative Approach to Reconstruction of the Lateral Nose

A 78-year-old man presented with a nodular basal cell carcinoma on the right alar crease. His medical history was unremarkable. After one stage of Mohs surgery, the site was cleared of tumor. On physical examination, the final defect measured 1.1 by 1.0 cm, extending from the anterior aspect of the alar crease to the start of the nasal supratip. The alar rim was preserved. The resulting full-thickness defect did not involve nasal perichondrium or cartilage. Given the small size of the lesion and location, how would you manage the defect (Figure 1)?

The Percutaneous Suspension Suture

The suspension suture is used frequently in facial cosmetic surgery and has been more recently used in reconstruction after Mohs micrographic surgery. A study by Robinson of 136 surgical defects repaired using this technique found the suspension suture beneficial to obtain linear closure, prevent the distortion of free margins, prevent tenting across concave surfaces, and fix the closure line at the junction of cosmetic units. The redistribution of tension to the surrounding edge also offers better feasibility of elliptic and flap closures with cosmesis intact.