A prospective evaluation of the effect of sample collection site on intraoperative parathormone monitoring during parathyroidectomy.

BACKGROUND: Sample collection site may affect the dynamics of intraoperative parathyroid hormone monitoring (IPM) and influence surgical decisions. METHODS: We prospectively studied 45 patients undergoing parathyroidectomy for primary hyperparathyroidism. The IPM cure criterion was a decrease in peripheral vein (PV) parathyroid hormone (PTH) of >50% at 10 minutes after gland excision. PTH samples were collected simultaneously from PV and central vein (CV) and compared for PTH decay, the incidence of >50% PTH decay, and the incidence of normal PTH values after gland excision. RESULTS: Mean PTH levels were significantly higher from the CV before and after gland excision. Mean PTH decay 10 minutes after gland excision was 89% PV versus 88% CV, resulting in mean PTH levels of 27 +/- 23 and 39 +/- 35 pg/mL, respectively (P < .0001). At 5 minutes, >50% decay in PTH was present in 98% PV versus 88% CV samples. By 10 minutes, the incidence of >50% PTH decay was equivalent (98%). This yielded normal range PTH levels from the PV versus CV in 90% versus 76% of patients at 5 minutes, 96% versus 89% at 10 minutes, and 95% versus 81% at 20 minutes. Of 45 patients, 44 (98%) are normocalcemic at a mean follow-up of 6.3 months. IPM predicted the single operative failure. CONCLUSIONS: CV sampling produces significantly higher PTH levels. Surgeons sampling from a PV may observe a >50% decrease in PTH and normal range PTH values starting 5 minutes after gland excision. Surgeons who sample from the CV and require normalization of PTH levels may have to wait longer and/or continue potentially unnecessary neck exploration.

Induction of transplantation tolerance by allogeneic donor-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells.

Several studies have shown that recipient-derived CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are involved in transplantation tolerance. However, it is not clear whether allogeneic donor-derived Tregs are able to regulate T cell alloreactivity after solid organ allograft transplantation. Related studies in experimental bone marrow transplantation have shown that allogeneic donor-derived Tregs are capable of promoting early and long-term allogeneic hematopoietic engraftment, accompanied by tolerance to donor and recipient antigens. However, in these models, donor-derived Tregs are syngeneic with respect to the T responder cells. The role of Tregs in solid organ transplantation models where recipient-derived T responder and donor-derived Tregs are allogeneic has been scarcely studied. In order to determine whether allogeneic Tregs were able to regulate T cell alloreactivity, CD4(+)CD25(-) and CD8(+) T responder cells were cultured with stimulator dendritic cells in several responder-stimulator strain combinations (C57BL/6-->BALB/c, BALB/c-->C57BL/6 and C3H-->BALB/c) in the presence of responder-derived, stimulator-derived or 3rd-party-derived Tregs. Then, the frequency of IFN-gamma+ alloreactive T cells was determined by means of ELISPOT assay. The results of this study demonstrate that, regardless of the responder-stimulator strain combination, both responder-derived and stimulator-derived Tregs, but not 3rd-party-derived Tregs, significantly inhibited CD4(+) and CD8(+) T cell alloreactivity. The effect of allogeneic stimulator-derived Tregs was dependent on IL-10 and TGF-beta and reversed by exogenous IL-2. In vivo experiments in nu/nu recipients reconstituted with CD4(+)CD25(-) T responder and Tregs showed that recipient and donor-derived, but not 3rd-party-derived Tregs, significantly enhanced skin allograft survival. Importantly, T cells from both recipient-derived and donor-derived Treg-reconstituted nu/nu recipients exhibited donor-specific unresponsiveness in vitro. These results show that allogeneic donor-derived Tregs significantly inhibit T cell alloreactivity and suggest their potential use in the induction of transplantation tolerance.

Intraoperative PTH monitoring in parathyroid hyperplasia requires stricter criteria for success.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) monitoring in parathyroidectomy for multigland disease is less clear than for single-gland disease. This study assesses the role of IOPTH for hyperplasia. METHODS: A prospective database revealed 45 patients with hyperplasia undergoing parathyroidectomy utilizing IOPTH from February 1999 to August 2003. RESULTS: Twenty-six females and 19 males had a mean age of 55 years. Twenty-two patients underwent total parathyroidectomy. Twenty-three patients underwent subtotal parathyroidectomy. Twenty-seven patients (60%) had a drop of IOPTH greater than 50% at 10 minutes after removal of all presumably abnormal parathyroid tissue. Nine additional patients (20%) had an IOPTH drop greater than 50%, but continued exploration revealed more abnormal tissue. Nine patients failed to decrease greater than 50%, and exploration was continued. A final IOPTH less than 35 pg/mL or a greater than 90% decrease from baseline was predictive of a successful operation in 40 patients. The 5 patients who did not meet this criteria remained hyperparathyroid. CONCLUSIONS: IOPTH identifies sporadic hyperplasia and guides completeness of resection for patients with known hyperplasia. However, more rigid criteria are required than for adenomas. Failure to achieve appropriate decreases in IOPTH should prompt further neck exploration or a search for a mediastinal gland.

Intraoperative total serum calcium levels, unlike intraoperative intact PTH levels, do not correlate with cure of hyperparathyroidism.

BACKGROUND: Intraoperative intact parathyroid hormone (iPTH) monitoring is useful in the operative management of hyperparathyroidism. Recent studies suggest that measurement of intraoperative total serum calcium (TSC) levels may be a more cost effective and readily available method of intraoperative guidance during neck dissection than iPTH levels, the gold standard. We compared the accuracy of intraoperative TSC to iPTH in predicting surgical cure during parathyroidectomy. PATIENTS AND METHODS: From September 1, 2001 to October 31, 2002, 88 parathyroidectomies were performed. iPTH and TSC were measured at the start of the operation, and at 5 and 10 min after gland removal. Data were compared, and trends were analyzed with respect to removal of abnormal parathyroid tissue as confirmed by pathology. One-way analysis of variance was used to determine if decreases in TSC were significant. RESULTS: The mean baseline iPTH level (418 +/- 610 pg/ml) dropped by 70% 5 min after removal of the abnormal glands (86 +/- 102 pg/ml) and by 85% at 10 min (39 +/- 39 pg/ml). The mean baseline TSC level (10.0 +/- 0.8 mg/dl) dropped by 4% at 5 min after removal of the abnormal glands (9.6 +/- 0.9 mg/dl) and remained at 4% at 10 min (9.6 +/- 0.8 mg/dl). iPTH dropped by > or =50% in 73 patients (83%) at 5 min and in 87 patients (99%) at 10 min after gland resection. TSC decreased below baseline at 5 min and remained below baseline at 10 min in only 47 patients (54%). In the remaining patients, intraoperative TSC changes were less predictable and did not respond consistently to resection of abnormal glands. CONCLUSIONS: The decreases in TSC during parathyroidectomy, if present, are minimal. Unlike iPTH levels, TSC levels do not consistently decrease at 5 and 10 min after gland resection. While attractive in terms of cost and availability, intraoperative TSC levels are not clinically reliable in confirming removal of abnormal parathyroid tissue.