Variables Affecting Basal Cell Carcinoma and Melanoma In Situ Excision Clearance: A Multi-institutional Retrospective Study.

BACKGROUND: The primary endpoint for surgical excision of skin cancer is the positive margin status. Tumor characteristics may explain much of this risk, but other important factors can include physician specialty. OBJECTIVE: To determine the variables affecting the success of a basal cell carcinoma (BCC) or melanoma in situ (MIS) excision. METHODS/MATERIALS: An 8-year, multicenter, retrospective study of 5,800 BCC or MIS excisions performed at 13 different Kaiser Permanente medical centers. The margin status was determined by searching final pathology diagnosis texts for phrases associated with positive margins. RESULTS: An incomplete excision rate was found in 23% of all specimens (BCC-22%, MIS-25%). Per specialty, the proportion of specimens with positive tumor margins was 24% for dermatology, 26% for plastic surgery, 28% for otolaryngology, and 12% for general surgery. General surgeons most often excised large tumors and tumors from truncal regions, 2 variables conferring lower odds of an incomplete excision. For non-Mohs procedures, dermatologists were no different than otolaryngologists or plastic surgeons in performing an incomplete BCC or MIS excision in all multivariate models (all p > .05). CONCLUSION: Intrinsic tumor characteristics may influence the success of achieving tumor-free resection margins more than the specialty of the provider.

Apremilast for the treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatoryarthropathy that affects joints and entheses andis associated with psoriasis (PsO). There are fiveclinical patterns of PsA: symmetrical polyarthritis,distal interphalangeal arthropathy, asymmetricaloligoarthritis, arthritis mutilans, and spondylitis, withor without sacroiliitis. Concerning PsA, the goals oftherapy are to control inflammation, prevent articulardamage, and reduce discomfort in the affected joints.Although there are many therapeutic options forthe treatment of PsAs, physicians most often beginwith nonsteroidal anti-inflammatory drugs (NSAIDs)for mild disease. Disease-modifying anti-rheumaticdrugs (DMARDS) are reserved for moderate to severedisease. Apremilast may be a useful option for somepatients.

Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence.

The small GTPase Rab7 promotes fusion events between late endosomes and lysosomes. Rab7 activity is regulated by extrinsic signals, most likely via effects on its guanine nucleotide exchange factor (GEF) or GTPase-activating protein (GAP). Based on their homology to the yeast proteins that regulate the Ypt7 GTP binding state, TBC1D15, and mammalian Vps39 (mVps39) have been suggested to function as the Rab7 GAP and GEF, respectively. We developed an effector pull-down assay to test this model. TBC1D15 functioned as a Rab7 GAP in cells, reducing Rab7 binding to its effector protein RILP, fragmenting the lysosome, and conferring resistance to growth factor withdrawal-induced cell death. In a cellular context, TBC1D15 GAP activity was selective for Rab7. TBC1D15 overexpression did not inhibit transferrin internalization or recycling, Rab7-independent processes that require Rab4, Rab5, and Rab11 activation. TBC1D15 was thus renamed Rab7-GAP. Contrary to expectations for a Rab7 GEF, mVps39 induced lysosomal clustering without increasing Rab7 GTP binding. Moreover, a dominant-negative mVps39 mutant fragmented the lysosome and promoted growth factor independence without decreasing Rab7-GTP levels. These findings suggest that a protein other than mVps39 serves as the Rab7 GEF. In summary, although only TBC1D15/Rab7-GAP altered Rab7-GTP levels, both Rab7-GAP and mVps39 regulate lysosomal morphology and play a role in maintaining growth factor dependence.