Prevalence, molecular markers, and outcome of bronchial squamous carcinoma in situ in high-risk subjects.

Bronchial squamous carcinoma in situ (CIS) is a preinvasive lesion that is thought to precede invasive carcinoma. We conducted prospective autofluorescence and white light bronchoscopy trials between 1992 and 2016 to assess the prevalence, molecular markers, and outcome of individuals with CIS and other preneoplastic bronchial lesions. Biopsies were evaluated at multiple levels and selected biopsies were tested for aneuploidy and DNA sequenced for TP53 mutation. Thirty-one individuals with CIS were identified. Twenty-two cases of CIS occurred in association with concurrent invasive carcinomas. Seven of the invasive tumors were radiographically occult. In two cases, CIS spread from the focus of invasive carcinoma into contralateral lung lobes, forming secondary invasive tumors. In nine cases, CIS occurred as isolated lesions and one progressed to invasive squamous carcinoma at the same site 40 months after discovery. In a second case, CIS was a precursor of carcinoma at a separate site in a different lobe. In seven cases CIS regressed to a lower grade or disappeared. High level chromosomal aneusomy was often associated with TP53 mutation and with invasive carcinoma. CIS most often occurs in association with invasive squamous carcinoma and may extend along the airways into distant lobes. In rare cases, CIS may be observed to directly transform into invasive carcinoma. CIS may be indicative of invasive tumor at a separate distant site. Isolated CIS may regress. Molecular changes parallel histological changes in CIS and may be used to map clonal expansion in the airways.

The role of lipoprotein(a) in clotting reactions during lipoprotein apheresis--A case report.

In individuals with familial hypercholesterolemia (FH) who are unable to reach a target low-density lipoprotein level on a drug regimen, lipoprotein apheresis (LA) may be the treatment of choice. Severe reactions involving clotting during LA are not well described in the literature. We report a case of a 63-year-old woman with FH and markedly elevated lipoprotein(a) (Lp[a]) levels who experienced such a reaction while undergoing LA with a dextran-sulfate cellulose column on the Kaneka MA-01 Liposorber system. Owing to the clotting as well as a blood pressure drop to <100 mm Hg systolic, the procedure was stopped early. Before her second procedure, she was given an increased loading dose of unfractionated heparin. She did not develop clotting during this second procedure. A growing body of literature on the role of Lp(a) in atherothrombotic complications and hemostasis supports a possible mechanism by which clotting in the instrument could occur during apheresis. Our patient's initial pretreatment Lp(a) was 3.5 times greater than the mean Lp(a) levels in patients with FH. This theory is consistent with our case in that the patient's Lp(a) levels progressively declined with each procedure, and she had no subsequent clotting.