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Robust, quick, and convenient intraoperative method to differentiate parathyroid tissue

Kikumori, Toyone Inaishi, Takahiro Miyajima, Noriyuki Shibata, Masahiro Takeuchi, Dai 名古屋大学

2020.02

概要

Background: Identification of parathyroid tissue during surgery is necessary for its preservation in situ or for autotransplantation to avoid postoperative hypoparathyroidism. Frozen sections are the gold standard for distinguishing parathyroid tissue from other tissues during thyroidectomy. Although frozen sections are very accurate, they are costly and require pathologists and technical staff. Parathyroid tissue is rich in mitochondria, which harbor Krebs-cycle enzymes such as aspartate aminotransferase. In contrast, lactate dehydrogenase is expressed ubiquitously. These 2 enzymes are measured routinely as “leaked” enzymes. We hypothesized that the aspartate aminotransferase–to–lactate dehydrogenase ratio in suspended tissue could distinguish parathyroid tissue from other tissues. Methods: We analyzed 94 specimens (43 parathyroid, 19 thyroid cancers, 13 normal lymph nodes, 10 adipose, 6 thyroid, and 3 miscellaneous tissues) from 55 patients who underwent thyroid or parathyroid surgery between March 2018 and June 2019 in our institution. Trace amounts of remnant parathyroid tissue from autotransplantation specimens were suspended in 1 mL of normal saline and measured for aspartate aminotransferase and lactate dehydrogenase. Approximately 1 mm3 of apparently distinct tissue minced by scissors (eg, thyroid gland, metastatic lymph node, etc) or washouts of needles used for preoperative aspiration biopsy were also measured for comparison. Results: The aspartate aminotransferase–to–lactate dehydrogenase ratios in suspended parathyroid tissue specimens were consistently greater than those of other tissues (P < .001, Mann-Whitney test); 0.27 was the optimal cutoff value with 100% sensitivity and specificity. Conclusion: This method distinguished parathyroid tissue quickly and conveniently from other tissues intraoperatively with minimum cost and without dedicated pathologic staff. This methodology may serve useful in decreasing the incidence of postoperative hypoparathyroidism, especially in settings with limited access to pathologists.

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参考文献

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Figure legend

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Scatterplot shows AST/LDH ratios in suspensions of various tissues, logarithmically

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plotted on the graph. The median and standard deviation (SD) for each of the tissue

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types are indicated at the bottom of the figure. Thyroid cancer: local recurrences,

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metastatic lymph nodes and primary tumor; miscellaneous tissues: median cervical cyst,

181

connective tissue and thymus. Bold horizontal line: optimal threshold value to

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distinguish parathyroid from other tissues (0.27). NA: not applicalble

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Acknowledgment

185

We thank Marla Brunker, from Edanz Group (www.edanzediting.com/ac), for editing a

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draft of this manuscript. This study has no funding to declare.

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Table 1

Patient characteristics, surgical indications and specimen information.

Sex (M : F )

Age (mean, (range))

11:44

54y, (13-86)

Pathology of surgical indication

Papillary thyroid cancer

Follicular adenoma or hyperplasia

Follicular thyroid cancer

C-cell hyperplasia

Medullary thyroid cancer

Parathyroid cancer*

Parathyroid adenoma†

Total

Analyzed Specimens

Parathyroid

Papillary thyroid cancer

Primary tumor

Local recurrence

Metastatic lymph node

Follicular thyroid cancer

Local recurrence

Normal lymph node

Normal thyroid

Adipose tissue

Miscellaneous

Median cervical cyst

Connective tissue

Thymus

Total

Thyroid was measured.

Adipose tissue was measured.

Table 2.

Patients’ age, sex, tissue types, AST and LDH values (IU/L) and AST/LDH ratios in the tissue suspension

parathyroid

age sex

62 F

34 F

40 F

13 M

42 F

67 F

33 F

47 F

31 F

24 M

56 F

14 F

34 M 25 F

Surgical Indication

FTC

PTC

CCH

PTC

FTC

AST (IU/L)

LDH (IU/L)

< 5†

129

157

< 5†

0.67

3.20

0.30

0.52

0.40

0.36

0.28

0.60

0.90

0.35

0.28

0.60

0.43

0.61

0.32

0.74

age sex

67 F

60 M

78 F

70 F

75 F

43 F

78 M

37 F

53 M

66 F

72 F

83 F 50 M

Surgical Indication

PTC

AST (IU/L)

LDH (IU/L)

133

159

134

142

< 5†

0.74

0.44

0.45

0.43

0.45

0.37

0.38

0.33

0.46

0.40

0.37

0.35

0.33

0.27

6.40

0.32

age sex

38 F

14 M

65 F

77 F

47 F

56 F

Surgical Indication

PTC

MTC

PTC

AST (IU/L)

LDH (IU/L)

216

153

0.59

1.09

0.36

0.47

0.27

0.51

0.46

0.37

0.47

0.32

0.36

AST/LDH

parathyroid

AST/LDH

parathyroid

AST/LDH

thyroid cancer

age sex

58 F

74 M* 74 F*

42 F

74 F

source

L (FTC)

AST (IU/L)

LDH (IU/L)

AST/LDH

254

293

0.12

0.05

0.04

0.14

thyroid cancer

age sex

56 F*

source

M (FTC)

AST (IU/L)

LDH (IU/L)

142

0.11

0.08

0.02

AST/LDH

86 F* 60 M*

67 F* 77 F*

74 M

56 F

67 F

85 F* 60 F*

75 F

68 F* 38 F* 38 F*

< 1‡

774

174

268

1806

209

1593

583

204

234

378

0.07

0.10

0.05

0.13

0.05

0.07

0.02

0.15

0.11

0.04

0.03

normal lymph node

age sex

42 F

14 F*

14 F

70 F

75 F

43 F

73 F*

14 M

77 F

47 F

Surgical Indication

PTC

MTC

PTC

AST (IU/L)

111

LDH (IU/L)

239

266

1836

218

103

135

236

126

274

AST/LDH

0.06

0.17

0.08

0.06

0.13

0.07

0.06

0.07

0.04

0.09

0.07

age sex

74 F

48 F

63 F

74 M

56 F

67F

78 F

53 F

50 M

38 F

Surgical Indication

PTC

ParaA# PTC

PTC

AST (IU/L)

LDH (IU/L)

140

231

101

AST/LDH

0.04

0.13

0.08

0.05

0.12

0.21

0.07

0.14

0.07

0.17

adipose tissue

normal thyroid

age sex

miscellaneous

40 F

Surgical Indication ParaC**

50 F*§ 50 Mǁ 14 M¶

42 F

56 F

47 F

78 F

47 F

PTC

MTC

AST (IU/L)

LDH (IU/L)

321

125

261

211

359

178

242

546

AST/LDH

0.10

0.13

0.12

0.11

0.23

0.13

0.04

0.06

0.07

All specimens of thyroid cancer were obtained from papillary thyroid cancers except for those indicated as follicular thyroid cancer

(FTC).

CCH: C-cell hyperplasia; FA: follicular adenoma or hyperplasia; L: local recurrence; M: metastatic lymph node; MTC: medullary thyroid

cancer; P: primary tumor; ParaA: parathyroid adenoma; ParaC: parathyroid cancer; PTC: papillary thyroid cancer.

* Specimen was obtained by preoperative fine needle aspiration biopsy.

† As concentration was below measurement limit (< 5 IU/L), 5 was used to calculate AST/LDH ratio.

‡ As concentration was below measurement limit (< 1 IU/L), 1 was used to calculate AST/LDH ratio.

§ Median cervical cyst

ǁ Connective tissue

¶ Thymus

# The AST/LDH ratio of this parathyroid adenoma was 0.63.

** The AST/LDH ratio of this parathyroid carcinoma was 0.21.

...

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Robust, quick, and convenient intraoperative method to differentiate parathyroid tissue

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Robust, quick, and convenient intraoperative method to differentiate parathyroid tissue

概要

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関連論文

Measurement of the AST to LD Ratio in Parathyroid Tissue Suspension Can Precisely Differentiate a Hyperfunctioning Parathyroid

Is cell block technique useful to predict histological type in patients with ovarian mass and/or body cavity fluids?

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