Comparison of tumor staging systems for cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) are at increased risk for poor outcomes as a result of cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: To compare the relative effectiveness of tumor staging systems for CSCC in a well-defined cohort of patients with CLL. METHODS: This retrospective outcomes study included 454 CSCC tumors among 161 patients with underlying CLL who were evaluated at a single academic medical center. Each tumor was staged according to Brigham and Women's Hospital (BWH), Union for International Cancer Control eighth edition (UICC8), and American Joint Committee on Cancer seventh edition (AJCC7) and eighth edition (AJCC8) criteria. We compared the effectiveness of tumor risk stratification according to each system. RESULTS: The BWH tumor staging system demonstrated superior risk stratification relative to the AJCC7 criteria (C-index, 0.725 vs 0.615; P = .036) and trended toward improved stratification relative to the AJCC8 (C-index, 0.796 vs 0.732; P = .214) and UICC8 (C-index, 0.725 vs 0.636; P = .096) staging systems. LIMITATIONS: Our study must be interpreted in the context of its retrospective design and relatively small number of adverse outcomes available for statistical analysis. CONCLUSIONS: The BWH system outperformed the AJCC7 criteria and trended toward superior risk stratification relative to both the AJCC8 and UICC8 criteria.

Early and Late Outcomes of Surgical Treatment in Carcinoid Heart Disease.

BACKGROUND: Symptoms and survival of patients with carcinoid syndrome have improved, but development of carcinoid heart disease (CaHD) continues to decrease survival. OBJECTIVES: This study aimed to analyze patient outcomes after valve surgery for CaHD during a 27-year period at 1 institution to determine early and late outcomes and opportunities for improved patient care. METHODS: We retrospectively studied the short-term and long-term outcomes of all consecutive patients with CaHD who underwent valve replacement at our institution between 1985 and 2012. RESULTS: The records of 195 patients with CaHD were analyzed. Pre-operative New York Heart Association class was III or IV in 125 of 178 patients (70%). All had tricuspid valve replacement (159 bioprostheses, 36 mechanical), and 157 underwent a pulmonary valve operation. Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%). There were 20 perioperative deaths (10%); after 2000, perioperative mortality was 6%. Survival rates (95% confidence intervals) at 1, 5, and 10 years were 69% (63% to 76%), 35% (28% to 43%), and 24% (18% to 32%), respectively. Overall mortality was associated with older age, cytotoxic chemotherapy, and tobacco use; 75% of survivors had symptomatic improvement at follow-up. Presymptomatic valve operation was not associated with late survival benefit. CONCLUSIONS: Operative mortality associated with valve replacement surgery for CaHD has decreased. Symptomatic and survival benefit is noted in most patients when CaHD is managed by an experienced multidisciplinary team.

Protein carbonylation and adipocyte mitochondrial function.

Carbonylation is the covalent, non-reversible modification of the side chains of cysteine, histidine, and lysine residues by lipid peroxidation end products such as 4-hydroxy- and 4-oxononenal. In adipose tissue the effects of such modifications are associated with increased oxidative stress and metabolic dysregulation centered on mitochondrial energy metabolism. To address the role of protein carbonylation in the pathogenesis of mitochondrial dysfunction, quantitative proteomics was employed to identify specific targets of carbonylation in GSTA4-silenced or overexpressing 3T3-L1 adipocytes. GSTA4-silenced adipocytes displayed elevated carbonylation of several key mitochondrial proteins including the phosphate carrier protein, NADH dehydrogenase 1α subcomplexes 2 and 3, translocase of inner mitochondrial membrane 50, and valyl-tRNA synthetase. Elevated protein carbonylation is accompanied by diminished complex I activity, impaired respiration, increased superoxide production, and a reduction in membrane potential without changes in mitochondrial number, area, or density. Silencing of the phosphate carrier or NADH dehydrogenase 1α subcomplexes 2 or 3 in 3T3-L1 cells results in decreased basal and maximal respiration. These results suggest that protein carbonylation plays a major instigating role in cytokine-dependent mitochondrial dysfunction and may be linked to the development of insulin resistance in the adipocyte.