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

TABLE 60-2. Clinical Success with Cryopreserved Parathyroid Autotransplants

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

Some patients may be included repeatedly in reports by Rothmund and Wagner.20 Grafts by Tolloczko41 were performed as cell suspensions. PTH = parathyroid hormone.

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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