Change in Eyelid Carcinoma T Category With Use of the 8th Versus 7th Edition of the American Joint Committee on Cancer: Cancer Staging Manual.

PURPOSE: To evaluate the frequency and nature of changes in T category when eyelid carcinomas are staged using the criteria in the 8th edition instead of the 7th edition of the American Joint Committee on Cancer staging manual. METHODS: Following Institutional Review Board approval, a retrospective review was conducted for all consecutive patients with the diagnosis of eyelid carcinoma treated by the senior author from January 2012 through December 2016. After a review of the clinical and pathologic data, each patient's disease was staged using both the 7th-edition and 8th-edition American Joint Committee on Cancer criteria for eyelid carcinomas. Changes in T categories between the 2 staging systems were examined. RESULTS: The review initially identified 167 patients with the diagnosis of eyelid carcinoma. Four patients were excluded because of incomplete or unclear data. The remaining 163 patients included 78 men and 85 women aged 21 to 97 years (median, 68 years). Eighty-two patients had basal cell carcinoma; 35, squamous cell carcinoma; 32, sebaceous carcinoma; 6, mucinous eccrine carcinoma; 3, Merkel cell carcinoma; 3, adenocarcinomas; and 2, adnexal carcinoma. The most common T category according to the 7th-edition criteria was T2a; the most common T category according to the 8th-edition criteria was T1b. Of the 163 patients, 64 (39%) had a lower T category with the 8th-edition than with the 7th-edition criteria, 59 (36%) had a higher T category, and 40 (25%) had the same T category. CONCLUSIONS: Application of the 8th-edition American Joint Committee on Cancer criteria for eyelid carcinoma changed the T category in 75% of patients. In general, the new 8th-edition American Joint Committee on Cancer tumor, node, metastasis (TNM) designations allow for a more objective and consistent designation of the T category.

Impact of Food and Drug Administration Approval of Vismodegib on Prevalence of Orbital Exenteration as a Necessary Surgical Treatment for Locally Advanced Periocular Basal Cell Carcinoma.

PURPOSE: To test the hypothesis that the US Food and Drug Administration approval of vismodegib in early 2012 has reduced the prevalence of orbital exenteration for locally advanced periocular basal cell carcinoma (BCC). METHODS: Following institutional review board approval, the authors reviewed clinical and pathological data of patients with locally advanced periocular BCC (T4 per the eyelid carcinoma classification in the 8th edition of the AJCC Cancer Staging Manual) treated by the senior author during 2006-2018. Patients were grouped into those who were treated before February 2012 ("before vismodegib approval") and those who presented later ("after vismodegib approval"). RESULTS: Forty-two patients with locally advanced periocular BCC were treated during the study period, of whom 31 were men. The median age at presentation was 66 years (range, 43-90). Twenty-two patients had T4a and 20 had T4b tumors. Thirteen patients were treated before and 29 were treated after vismodegib approval. The 2 groups did not differ in age distribution (p = 0.164), sex distribution (p = 0.270), prevalence of recurrent tumor at presentation (p = 0.317), or duration of treatment with vismodegib (p = 0.605). Orbital exenteration was significantly more prevalent in patients treated before vismodegib approval than after (46% vs. 10%, p = 0.016), and vismodegib treatment was significantly more prevalent in patients treated after vismodegib approval than before (when vismodegib was given in clinical trials; 69% vs. 23%, p = 0.008). There was a trend toward more patients retaining their eyes at last follow-up in patients treated after vismodegib approval (83% vs. 54%, p = 0.066). CONCLUSIONS: The prevalence of orbital exenteration as a necessary surgical procedure in patients with a locally advanced periocular BCC has fallen since the Food and Drug Administration approval of vismodegib. Although vismodegib is not specifically approved for organ-sparing, it has changed the authors' practice and enabled eye preservation in patients with locally advanced periocular BCC, who would otherwise require an orbital exenteration.

Visual perception as retrospective Bayesian decoding from high- to low-level features.

When a stimulus is presented, its encoding is known to progress from low- to high-level features. How these features are decoded to produce perception is less clear, and most models assume that decoding follows the same low- to high-level hierarchy of encoding. There are also theories arguing for global precedence, reversed hierarchy, or bidirectional processing, but they are descriptive without quantitative comparison with human perception. Moreover, observers often inspect different parts of a scene sequentially to form overall perception, suggesting that perceptual decoding requires working memory, yet few models consider how working-memory properties may affect decoding hierarchy. We probed decoding hierarchy by comparing absolute judgments of single orientations and relative/ordinal judgments between two sequentially presented orientations. We found that lower-level, absolute judgments failed to account for higher-level, relative/ordinal judgments. However, when ordinal judgment was used to retrospectively decode memory representations of absolute orientations, striking aspects of absolute judgments, including the correlation and forward/backward aftereffects between two reported orientations in a trial, were explained. We propose that the brain prioritizes decoding of higher-level features because they are more behaviorally relevant, and more invariant and categorical, and thus easier to specify and maintain in noisy working memory, and that more reliable higher-level decoding constrains less reliable lower-level decoding.

Consistent sex-dependent effects of PKMζ gene ablation and pharmacological inhibition on the maintenance of referred pain.

BACKGROUND: Persistently active PKMζ has been implicated in maintaining spinal nociceptive sensitization that underlies pain hypersensitivity. However, evidence for PKMζ in the maintenance of pain hypersensitivity comes exclusively from short-term studies in males using pharmacological agents of questionable selectivity. The present study examines the contribution of PKMζ to long-lasting allodynia associated with neuropathic, inflammatory, or referred visceral and muscle pain in males and females using pharmacological inhibition or genetic ablation. RESULTS: Pharmacological inhibition or genetic ablation of PKMζ reduced mild formalin pain and slowly developing contralateral allodynia in nerve-injured rats, but not moderate formalin pain or ipsilateral allodynia in models of neuropathic and inflammatory pain. Pharmacological inhibition or genetic ablation of PKMζ also effectively reduced referred visceral and muscle pain in male, but not in female mice and rats. CONCLUSION: We show pharmacological inhibition and genetic ablation of PKMζ consistently attenuate long-lasting pain hypersensitivity. However, differential effects in models of referred versus inflammatory and neuropathic pain, and in males versus females, highlight the roles of afferent input-dependent masking and sex differences in the maintenance of pain hypersensitivity.