Indications for Transplantation with Cryopreserved Tissue
The indications for autotransplantation with cryopreserved tissue are straightforward: persistent, "permanent" hypocalcemia in patients for whom cryopreserved tissue is available. There is no fully agreed-on definition of permanent hypocalcemia; however, dependence on oral calcium and vitamin D
Study |
No. of Patients |
No. (%) of Functioning Grafts |
Proof of Success |
Caccitolo et al37 |
13 (15 grafts) |
6 (6 grafts) (40) |
Calcium and PTH |
Carty and Norton38 |
17 |
12 (71) | |
Higgins et al39 |
3 |
2 (67) |
PTH |
Mozes et al40 |
1 |
1 (100) |
Calcium and PTH |
Rothmund and Wagner20 |
7 |
5(71) |
Calcium and PTH |
Saxe et al21 |
12 |
7(58) |
Calcium and PTH |
Tolloczko et al41 |
23 |
18 (78) |
PTH |
Wagner et als |
25 |
16 (64) |
Calcium |
Walgenbach et al42 |
2 |
2 (100) |
PTH |
Wells et al43 |
1 |
1 (100) |
PTH |
Wells et al44 |
6 |
5(83) |
Calcium and PTH |
TABLE 60-3. Functional Comparison of Cryopreserved versus Fresh Parathyroid Tissue | ||
Study |
Model |
Function |
Brennan et al33 |
Cell suspension (human) |
Similar calcium-mediated PTH suppression in four of six évaluable |
patients | ||
Brennan et al19 |
Cell suspension (human) |
Preservation of calcium-mediated PTH suppression |
Herrera et al" |
Cell suspension (human) |
Preservation of calcium-mediated PTH suppression |
Hetrakul et al!7 |
Mitochondria (human) |
Loss of mitochondrial sestamibi uptake in cryopreserved versus |
fresh parathyroid tissue | ||
McHenry et al15 |
Ceti suspension (bovine) |
Preservation of calcium-mediated PTH suppression |
Preservation of calcium-mediated steady-state cytosoltc calcium | ||
concentration | ||
Rothmund and Wagner20 |
Cell suspension (human) |
Similar calcium-mediated suppression in 12 patients |
Saxe13 |
Cell suspension (human) |
Preservation of calcium-mediated PTH suppression |
Saxe and Gibson16 |
Cell suspension (human) |
Preservation of lithium-stimulated tritiated thymidine incorporation |
Wagner et al12 |
Cell suspension (human) |
Preservation of calcium-mediated PTH suppression |
Similar release of PTH per cell | ||
PTH = parathyroid hormone |
for 6 months seems reasonable. Patients with disabling symptoms may undergo transplantation sooner.21 Measurement of parathyroid hormone to distinguish postoperative parathyroid hormone deficiency from "bone hunger" is warranted before the physician embarks on autotransplantation. Although routine cryopreservation is difficult to justify because of the low incidence of postoperative hypocalcemia, surgeons managing patients at higher risk for hypocalcemia should be knowledgeable about techniques of cryopreservation and parathyroid transplantation, and their institutions should have appropriate facilities. An informal survey of several clinical investigators reported rather similar impressions: resected parathyroid tissue is cryopreserved, if ever, only from patients at high risk for postoperative hypoparathyroidism, and only a handful of patients have undergone autotransplantation with cryopreserved tissue. As discussed in Chapter 59, patients well recognized as being at higher risk for postoperative hypoparathyroidism are those undergoing
IN VITRO PTH RELEASE BY HUMAN PARATHYROID CELLS
IN VITRO PTH RELEASE BY HUMAN PARATHYROID CELLS

FIGURE 60-1. Comparison of suppression of parathyroid hormone (PTH) release in vitro in both fresh tissue (O) and after 20 to 220 days of cryopreservation of tissue (A); mean of five patients at each point. (From Brennan MF, Brown EM. Prediction of in vivo function of human parathyroid tissue autografts by in vitro testing. World J Surg 1980;4:748.)
FIGURE 60-1. Comparison of suppression of parathyroid hormone (PTH) release in vitro in both fresh tissue (O) and after 20 to 220 days of cryopreservation of tissue (A); mean of five patients at each point. (From Brennan MF, Brown EM. Prediction of in vivo function of human parathyroid tissue autografts by in vitro testing. World J Surg 1980;4:748.)
reoperative thyroid surgery, those who have multiple hyperplastic parathyroid glands resected, and those undergoing reoperation for persistent or recurrent hyperparathyroidism.
Thyroid Disease
Transplantation with cryopreserved tissue does not play a role in either primary or secondary operations for thyroid disease. Recognition that parathyroid tissue has become devascular-ized warrants immediate transplantation of the tenuous parathyroid to the sternocleidomastoid muscle. Frozen section analysis of a small piece of the tissue to be transplanted is mandatory. As pointed out by Lahey,24 it can be difficult to distinguish a lymph node with metastatic thyroid cancer from a parathyroid gland.
Multiple-Gland Disease: Initial Surgery
Multiple-gland disease can be anticipated in patients with multiple endocrine neoplasias, familial disease, and secondary hyperparathyroidism. Two surgical strategies are widely used: (1) subtotal (3.5-gland excision) parathyroidectomy leaving tissue attached to its native blood supply and (2) total parathyroidectomy and autotransplantation to forearm muscles or subcutaneously. Regardless of the strategy selected, cryopreservation of resected parathyroid tissue as a backup is warranted. Autotransplantation with fresh tissue is not uniformly successful, as reflected by an incidence of postoperative hypoparathyroidism of approximately 10% in patients undergoing total parathyroidectomy with immediate autotransplantation.5 Autotransplantation with biopsy-proven cryopreserved tissue offers the patient a second chance to be free from calcium supplements.
Reoperative Parathyroid Surgery
An important part of planning reoperative parathyroid surgery is the review of operative and pathology notes by the surgeon and the review of resected tissue by a pathologist. Should it be determined that the patient's only functioning parathyroid tissue is a single remaining adenoma, resection with immediate transplantation of a portion of the adenoma and
TABLE 60-4. Use of Cryopreserved Parathyroid Tissue for Research
Study
Model
Result
Hetrakul et al17
Kobayashi et al30 Martin et al38 Saxe13
Saxe and Gibson16 Brennan et al33 Saxe et ai27 Saxe et al29 Saxe et al31
Minced tissue "Mitochondrial activity is the major component of sestamibi uptake by human parathyroid tissue in patients with hyperparathyroidism" Cell suspension Used to generate microcapsules of parathyroid tissue Cell suspension No effect of cryopreservation upon antigenicity
Cell suspension Phorbol ester suppresses low-calcium-mediated and augments high-calcium-mediated PTH release
Cell suspension Lithium increases tritiated thymidine incorporation in abnormal human tissue
Cell suspension Preservation of calcium-mediated PTH release
Cell suspension No change in immunogenicity
Cell suspension No in vitro effect of Cimetidine
Cell suspension Minimal or no expression of estrogen receptors
PTH = parathyroid hormone.
cryopreservation of the remaining tissue are preferred over angiographic ablation.
Another situation that may be anticipated by a review of operative documents and histologic slides is that of reoperation for multiple-gland disease. Saxe and Brennan25 reported a 54% incidence of spontaneous normocalcemia and a 12% incidence of persistent hypercalcemia in 26 such patients who underwent attempted total parathyroidectomy without immediate autotransplantation. Of particular interest were 13 patients who had histologically documented four-gland resections. Fully 69% of those patients remained normocal-cemic (seven patients) or hypercalcemic (two patients) without calcium supplementation or autotransplantation. This indicates that in this setting even patients undergoing intentional removal of all parathyroid tissue may (unpredictably) have residual tissue. The seven normocalcemic patients might well have become hypercalcemic had they received immediate autotransplants. The authors concluded that for patients undergoing intentional "total parathyroidectomy" at reoperation for multiple-gland disease, a prediction of inevitable hypocalcemia is unwarranted and immediate autotransplantation with fresh tissue is unwise. They recommended restricting autotransplantation (with cryopreserved tissue) to patients with documented hypoparathyroidism.

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