Roy C. Grekin

Temporal Dissection of Tumorigenesis in Primary Cancers

Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.

Antibiotic prophylaxis in dermatologic surgery

Antibiotic prophylaxis is generally administered either to prevent wound infection or to hinder the development of endocarditis. Although the use of antibiotics in certain circumstances to prevent wound infection can be straightforward, there are other circumstances in which the decision to use antibiotics is much less clear. Endocarditis prophylaxis has traditionally been based on the American Heart Associations guidelines, which do not cover dermatologic surgery. This article discusses the rationale and controversies surrounding the use of antibiotic prophylaxis for prevention of both wound infection and endocarditis, reviews the few studies that pertain to dermatology, and provides recommendations for antibiotic prophylaxis on a case-by-case basis for those who perform dermatologic surgery.

Local anesthesia in dermatologic surgery.

With the growth of dermatologic surgery the appropriate use of local anesthesia is becoming an important issue. Thoughtful use of local anesthesia can improve the patients experience and facilitate the surgical procedure. In this review we discuss historical and pharmacologic aspects of local anesthetic agents. Emphasis is placed on clinical considerations, including contraindications, toxic reactions, and detailed descriptions of anesthetic use.

Retinoid therapy is associated with excess granulation tissue responses

In our clinical trials of isotretinoin therapy for cystic acne and etretinate treatment of psoriasis, eight patients had growth of excessive granulation tissue. The granulation tissue was found in resolving acne lesions in one patient taking isotretinoin. Among the psoriatic patients taking etretinate, the granulation tissue usually was seen adjacent to nail plates. In two patients, the side effect caused them to stop retinoid therapy. The tissue response did not appear to be related to the daily or cumulative retinoid dose.

Hyperthermic injury to adipocyte cells by selective heating of subcutaneous fat with a novel radiofrequency device: feasibility studies.

The main objective of the present study is to demonstrate the feasibility of utilizing a novel non‐invasive radiofrequency (RF) device to induce lethal thermal damage to subcutaneous adipose tissue only by establishing a controlled electric field that heats up fat preferentially.

Genital tumors: Their management by micrographic surgery

Genital tumors represent a special group requiring effective and curative treatment while functional and cosmetic demands require tissue sparing techniques. For these reasons, micrographic surgery is indicated. Over the past 5 years we have treated 24 such patients utilizing standard techniques for micrographic surgery. The patient population included twenty male and four female patients with ages ranging from 27 to 80 years. Histologically confirmed diagnoses included squamous cell carcinoma, Bowens disease, verrucous carcinoma, basal cell carcinoma, Pagets disease, and leiomyosarcoma. These were located on the penis, scrotum, perineum, and buttocks. Seven of these patients were considered to have recurrent tumors. Preexisting conditions existed in 6 patients, including balantis xerotica obliterans, trauma, decubitus ulcer, and hidradenitis suppurativa. All surgery was performed under local anesthesia in the cutaneous surgery unit. Average pretreatment tumor size was 2.0 X 1.9 cm. Average postoperative defect size was 4.5 X 3.7 cm. Tumors were excised with an average of three stages and 18 sections. Most defects (65%) were allowed to heal by secondary intention, five (21%) were closed primarily, and three were referred for closure. After surgery five patients developed metastases in their regional lymphatic system. No patients developed local recurrence. Micrographic surgery is a most useful treatment modality in patients with genital tumors for control of local disease. However, patients with squamous cell carcinoma should be considered for elective regional lymph node biopsy and/or dissection in conjunction with micrographically controlled excision of the primary tumor.

Treatment of adenoma sebaceum with the copper vapor laser

BACKGROUND Angiofibromas of the central part of the face (adenoma sebaceum) occur pathognomonically in tuberous sclerosis, causing significant cosmetic and hygienic morbidity. Treatment has included excision, dermabrasion, cryosurgery, carbon dioxide laser, and argon laser. Copper vapor lasers emit light at 511 nm (green) ad 578 nm (yellow), useful for treating pigmented and vascular lesions, respectively. OBJECTIVE Because of the vascular nature and progressive pigmentation of adenoma sebaceum, we examined the utility of the copper vapor laser in treating this disorder. METHODS Nine patients with adenoma sebaceum were treated with the copper vapor laser. Individual lesions were treated with the yellow light (578 nm) at 0.4 to 0.6 mW. Pigmented lesions or lesions resistant to treatment were treated with the green light (511 nm) at 0.4 to 0.9 mW. Intervals between treatments were at least 6 weeks. RESULTS Good to excellent cosmetic results were seen in all treated patients. Scarring or hyperpigmentation occurred in none of the patients. Most patients required additional treatments with the copper vapor laser as new lesions developed. CONCLUSION The copper vapor laser is safe and effective for the treatment of adenoma sebaceum in tuberous slerosis.

Synthetic membranes and cultured keratinocyte grafts

Significant progress has been made in skin replacement options in the past several decades. Although initially various materials have been used mainly for burn coverage, their application to dermatologic practice has increased significantly. We review the research, progress, and other aspects of wound coverage with synthetic membranes and cultured epithelial sheets in both burn and nonburn wound management.

Bleeding complications in dermatologic surgery.

Although the overall incidence is low, bleeding complications in dermatologic surgery can occur and be the source of significant patient morbidity. In this article, we summarize the key aspects of preoperative assessment of patients at risk for bleeding. A review of current issues and literature regarding safe continuation of anticoagulant and antiplatelet medications in dermatologic surgery patients is also presented. In addition, principles for management of bleeding events, should they occur, are also highlighted.

Etretinate therapy stimulates deposition of mucus-like material in epidermis of patients with psoriasis

During therapy for psoriasis with the oral aromatic retinoid etretinate, a finely granular material was detected by electron microscopic examination of the epidermis of ten patients. Since this amorphous substance has some of the ultrastructural characteristics of mucin, it is called mucus-like material (MLM). MLM occurs occasionally in untreated psoriatic lesions; however, its deposition is enhanced by etretinate therapy. While MLM has not been fully characterized, evidence exists for the possibilities that it represents either cell products (such as mucin, or carbohydrates associated with the cell surface) or an exudate infiltrating the epidermis.