Conventional immunosuppressive drugs have been used effectively to prevent immunologic rejection in organ transplantation. Individuals taking these drugs are at risk, however, for the development and recurrence of cancer. In the present study we show that the new immunosuppressive drug rapamycin (RAPA) may reduce the risk of cancer development while simultaneously providing effective immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses of RAPA effectively controlled the growth of established tumors. In contrast, the most widely recognized immunosuppressive drug, cyclosporine, promoted tumor growth. From a mechanistic perspective, RAPA showed antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients.
Background
Despite improved preoperative diagnostics, incidental postoperative detection of differentiated thyroid cancer in the final histology is still common. In most of these cases, completion thyroidectomy is recommended by national and international guidelines, although secondary surgery is associated with an increased operative risk. The optimal timing of completion thyroidectomy is still controversial.
Methods
Between January 1993 and December 2009, a total of 128 patients underwent completion thyroidectomy for differentiated thyroid carcinoma: papillary (n = 87) and follicular (n = 41). These patients were divided into five groups according to the time of the completion thyroidectomy after primary surgery (groups A, 1–3 days; B, 4–7 days; C, 1–7 weeks; D, 7–12 weeks; E, >3 months). Clinical complications and oncologic outcomes were analyzed. The mean follow‐up was 82.5 ± 17 months.
Results
The overall rates of transient and persistent postoperative hypocalcemia were 7.0 and 3.1%, respectively. The rates of persistent hypocalcemia were significantly increased in groups B, C, and D in comparison to those in groups A and E (p < 0.003). The hypocalcemia rates were 7.1, 4.5, and 3.8% versus 0%, respectively. Transient or persistent vocal cord paresis was observed in eight (6.2%) and four patients (3.1%), respectively. The incidence of persistent vocal cord paresis (VCP) was significantly higher in groups B, C, and D than in groups A and E (p < 0.003). The VCP rates were 7.1, 4.5, and 3.8% versus 0%, respectively. There was no significant difference regarding survival or recurrence among the five groups.
Conclusions
Considering perioperative morbidity and oncologic outcomes, completion thyroidectomy should be performed either within 3 days or beyond 3 months after primary surgery.
+ NKT cells induced cell death of colon-infiltrating lymphocytes isolated from diseased mice. This effect was inhibited in the presence of either anti-CD1d or anti-programmed death ligand-1 (PD-L1) blocking antibodies. The specific potency of DX5 + NKT cells in regulating chronic colitis in two mouse models is demonstrated. In vitro testing suggests that DX5 + NKT cells activated by CD1d induce cell death of colitis-inducing lymphocytes, which is mediated through PD-L1. Therefore, DX5+ NKT cells could be important in the regulation of immune responses associated with chronic colitis.
CEUS represents a highly reliable, noninvasive and nonradioactive diagnostic tool for localization of pathological parathyroid glands in patients with pHPT. Even in the presence of CG, previous neck surgery, or double adenomas, CEUS has a high sensitivity.
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