Jerome Hill

Malignant Melanoma 2003Predisposition, Diagnosis, Prognosis, and Staging

The incidence and mortality of melanoma has seemed to level off for certain groups after a steady increase during the last 50 years. This trend is suspected to be secondary to education efforts aimed at prevention and better detection and removal of thin, biologically benign melanomas. Since no effective systemic therapies exist for metastatic melanoma, early detection and removal of thin melanomas offer the best chance of cure. For thicker melanomas, sentinel lymph node biopsy has improved the accuracy of staging and prognostic evaluation. However, approximately one third of patients diagnosed with metastatic melanomas present without previous regional lymph node metastases. As the genomic understanding of melanomas pathogenesis grows, new methods likely will be developed to more accurately identify the people at risk for melanoma, those who have high-risk melanomas, and those who have disseminated disease. We review current and potential biomarkers useful for the screening for and prevention, diagnosis, staging, and prognosis of melanoma.

Influence of Cholesterol Oxidation Derivatives on Membrane Bound Enzymes in Cultured Aortic Smooth Muscle Cells

Abstract Cholestane-3β,5α,6β-triol and 25-hydroxycholesterol are two of the most cytotoxic and also relatively abundant of the autoxidation derivatives of cholesterol. Cultured aortic smooth muscle cells which were incubated with 10 μg/ml of either sterol for 24 to 48 hr showed a marked decrease of 5′-nucleotidase activity in isolated crude membranes. It was further demonstrated that 5′-nucleotidase activity was also markedly decreased in plasma membrane-enriched fractions when cells were incubated with cholestane-3β,5α,6β-triol. Na+, K+-ATPase activity in crude membranes showed a significant decrease (32%) only in cells incubated with cholestane-3β,5α,6β-triol for 48 hr. There was no effect on Na+, K+-ATPase activity in cells incubated for 24 hr with either sterol.

Effects of cholesterol autoxidation derivatives on hexose transport in cultured aortic smooth muscle cells

Several cholesterol autoxidation derivatives known to be cytotoxic to arterial smooth muscle cells both in vivo and in vitro were shown to inhibit hexose transport in these cells in culture. Cholestane-3 beta, 5 alpha, 6 beta-triol was the most potent inhibitory sterol. The rapid onset of inhibition (15 min) and the reversibility of the effect upon removal of the sterol from the tissue culture medium suggests that the effect may be due to incorporation of the sterol into the plasma membrane. 25-Hydroxycholesterol, a potent inhibitor of sterol biosynthesis in cultured arterial smooth muscle cells, did not affect hexose transport up to 8 hr of incubation. The cytotoxic effect of 25-hydroxycholesterol, therefore, may be a consequence of the reduced sterol biosynthesis caused by this sterol.

Development of metastatic Crohn's disease of the skin while on Anti‐TNF biologics

Metastatic Crohn’s disease (CD) is a rare extraintestinal manifestation of CD. Metastatic CD is a sterile granulomatous skin lesion arising at sites discontinuous from the gastrointestinal tract. Metastatic CD is most commonly observed in the lower extremities and intertriginous areas. Patients with either CD or rheumatoid arthritis, treated with anti-tumor necrosis factor (TNF) biologics, have been described to develop a number of dermatologic disorders, including eczema and psoriasis. The development of metastatic CD in a patient while being treated with anti-TNF biologics has not been previously described. We report a patient with CD who developed ulcerated lower extremity nodules, thought to be pyoderma gangrenosum, while being treated with infliximab and subsequently with adalimumab. Six years later the lower extremity skin lesions were demonstrated to be metastatic CD. Our patient is a 37-year-old female who has had moderate-to-severe, stricturing CD of the terminal ileum for over 20 years. Her CD was initially maintained in remission on an oral mesalamine plus oral, rapidly metabolized, budesonide, as needed for many years. She subsequently had frequent exacerbations of her CD, requiring treatment with steroids and antibiotics. Therefore, she was started on infliximab with excellent symptomatic improvement. After 5 years of infliximab therapy, she developed lower extremity, erythematous, ulcerated nodules that were biopsied and diagnosed as pyoderma gangrenosum. The lower extremity skin lesions were treated with injections of Kenalog and a topical cream without significant improvement. She simultaneously developed mild psoriasis on her back. Due to severe diarrhea and worsening of the ulcerated nodules on her lower extremities, 6-mercaptopurine was added to the infliximab therapy. The lower extremity skin lesions developed recurrent bacterial superinfections requiring episodic courses of antibiotic therapy. Infliximab was discontinued and she was then treated with adalimumab for 2 years. During this time there was no improvement in either the lower extremity skin lesions or the psoriasis. Because of continued symptoms due to refractory CD, she then underwent an ileocolonic resection. Following surgery, despite improvement in her CD symptoms, she continued to have both the severe lower extremity skin lesions (Fig. 1) and also the psoriasis. Therefore, a biopsy was performed, which demonstrated a suppurative and granulomatous dermatitis with associated panniculitis (Fig. 2). Special stains for acidfast bacteria, fungi, and bacteria were negative, which excluded infectious etiologies. She was diagnosed as having metastatic CD involving the lower extremities. Methotrexate 25 mg intramuscularly weekly in combination with the previous ileocolectomy and also prior discontinuation of the antiTNF biologics, finally lead to improvement in both the metastatic CD (Fig. 3) and also the psoriasis. The development of metastatic CD of the skin while on anti-TNF biologics has not previously been reported. Our patient developed metastatic CD involving the lower extremities, while she was being treated with infliximab for 5 years and subsequently with adalimumab for 2 years. She simultaneously developed mild psoriasis on her back. The development of multiple types of skin lesions in patients treated with anti-TNF biologics has been reported for many years. Psoriasis and eczema are the two most commonly observed skin lesions induced by anti-TNF biologics. Additional skin lesions observed in patients treated with anti-TNF biologics have included dermatitis sicca, pityriasis FIGURE 1. Appearance of metastatic CD lesion on the lower legs.