No abstract

A standardized, reproducible Ivy bleeding time technic has been described which permits one to obtain accurate bleeding time data in man. The technic was used to standardize an aspirin tolerance test in which 60 normal males had a control bleeding time; were given, on a double blind basis, either placebo or 1 Gm. of aspirin, and had a second bleeding time 2 hours later. The control values were: mean, 5 min.; mean ± 2 st. dev., 2 min., 30 sec. to 10 min. The values after placebo were: mean, 5 min., 30 sec.; mean ± 2 st. dev., 2 min., 30 sec. to 11 min. The values after aspirin were: mean, 9 min., 30 sec.; mean ± 2 st. dev., 4 min. to 21 min. The difference between the mean bleeding time after placebo and after aspirin was highly significant (p < 0.001). The distribution of the bleeding times after aspirin suggested that normal subjects do not respond to aspirin as a single population. The degree of prolongation of the bleeding time and the large size of the drops of blood observed in some subjects suggested to us that small amounts of aspirin may exert a significant effect upon hemostasis in normal individuals.

disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE To develop recommendations for the care of adults with EMPD.EVIDENCE REVIEW A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGSThe key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. ( 5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.CONCLUSIONS AND RELEVANCE Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Background: Current staging systems for cutaneous squamous cell carcinoma (cSCC) have limited positive predictive value for identifying patients who will experience metastasis.Objective: To develop and validate a gene expression profile (GEP) test for predicting risk for metastasis in localized, high-risk cSCC with the goal of improving risk-directed patient management.Methods: Archival formalin-fixed paraffin-embedded primary cSCC tissue and clinicopathologic data (n = 586) were collected from 23 independent centers in a prospectively designed study. A GEP signature