No abstract

The overall clinical and biochemical features of PHPT in Chinese patients are still classic, but the disease is now evolving into a more asymptomatic type. The incidental parathyroid lesion captured by routine neck ultrasonography was the leading cause for such a dramatic change. The high incidence of parathyroid carcinoma is now decreasing.

LIM domain Only 2 (Lmo2) is frequently deregulated in sporadic and gene therapy-induced acute T-cell lymphoblastic leukemia (T-ALL) where its overexpression is an important initiating mutational event. In transgenic and retroviral mouse models, Lmo2 expression can be enforced in multiple hematopoietic lineages but leukemia only arises from T cells. These data suggest that Lmo2 confers clonal growth advantage in T-cell progenitors. We analyzed proliferation, differentiation, and cell death in CD2-Lmo2 transgenic thymic progenitor cells to understand the cellular effects of enforced Lmo2 expression. Most impressively, Lmo2 transgenic T-cell progenitor cells were blocked in differentiation, quiescent, and immortalized in vitro on OP9-DL1 stromal cells. These cellular effects were concordant with a transcriptional signature in Lmo2 transgenic T-cell progenitor cells that is also present in hematopoietic stem cells and Early T-cell Precursor ALL. These results are significant in light of the crucial role of Lmo2 in the maintenance of the hematopoietic stem cell. The cellular effects and transcriptional effects have implications for LMO2-dependent leukemogenesis and the treatment of LMO2-induced T-ALL.

Key Points AE induces hematopoietic self-renewal through a COX/prostaglandin E2/β-catenin signaling pathway. Clinically available COX inhibitors may target AML stem cells and suppress AML of various karyotypes.

Summary Objective Parathyroid carcinoma (PC) is a rare disease which is difficult to diagnose preoperatively and predict prognosis. The goal of this study was to analyse the preoperative predictive factors and prognostic factors in PC patients and to evaluate the possibility of diagnosing PC preoperatively. Design, Setting and Patients This is a retrospective study from Jan 2000 to Aug 2015 conducted in Shanghai Ruijin Hospital. Measurements Comparisons were made between 40 parathyroid carcinoma patients and 282 patients with benign parathyroid lesions during the same period. All patients underwent parathyroid surgery, and the results were certified by paraffin pathology. Prognostic factors were analysed in the 40 PC patients. Results Patients with higher levels of intact parathyroid hormone (P < 0·001, OR = 1·001, CI: 1·000–1·002), calcium (P = 0·008, OR = 3·395, CI: 1·382–8·341) and a larger parathyroid volume (P = 0·001, OR = 2·023, CI: 1·333–3·071) were more likely to have PC. Local excision (P = 0·008, OR = 4·992, CI: 1·533–16·252), stage III in the Schulte staging system (P = 0·039, OR = 9·600, CI: 1·12–82·322), high risk in the Schulte Risk Classification (P = 0·012, OR = 5·466, CI: 1·448–20·628) and first surgery by other medical teams (P = 0·008, OR = 4·992, CI: 1·496–15·037) were associated with PC recurrence. Calcium (P = 0·01, OR = 7·270, CI: 1·611–32·812), intact parathyroid hormone (P = 0·037, OR = 1·001, CI: 1·000–1·001), local excision (P = 0·009, OR = 6·875, CI: 1·633–28·936) and recurrence (P = 0·014, OR = 7·762, CI: 1·504–40·055) were associated with death. Conclusions A preoperative diagnostic system may provide a new method to distinguish PC from benign parathyroid lesions before surgery. For PC patients who did not undergo en‐bloc resection at first operation, timely further surgery may offer a second chance of cure. Early diagnosis and surgery are pivotal to reduce mortality in PC patients.