臺灣博碩士論文加值系統

甲狀腺功能和結構異常是內分泌系統中最常見的疾病。在功能方面，葛雷夫氏症是造成甲狀腺亢進最主要原因之一，它的特徵是甲狀腺腫與機能亢進，病人可能合併有甲狀腺眼病變或脛前黏液水腫。目前並沒有好的工具可以研究記錄脛前黏液水腫或客觀描述眼病變的發炎程度，這對治療方式的選擇和發展是一大限制。在構造異常方面，甲狀腺乳突癌是最常見的甲狀腺癌，目前所有的預後評估工具都需要等到術後根據手術觀察記錄和病理報告才有辦法使用，這對手術本身甲狀腺切除範圍、淋巴節廓清與否的選擇並沒有幫助。本研究嘗試解決這些重要的臨床問題。
在葛雷夫氏症方面，電腦化遠紅外線熱影像可以度量局部的溫度，我們嘗試用它來協助觀察記錄發炎程度。脛前黏液水腫方面收納了87個有或沒有脛前黏液水腫的葛雷夫氏症病人與14個正常人，以遠紅外線熱影像觀察其前脛。遠紅外線熱影像顯示在脛前黏液水腫處和某些以肉眼觀察無脛前黏液水腫的葛雷夫氏症病人的前脛有異常的局部低溫。抗甲狀腺刺激素抗體值與溫度降低的程度有正相關(p=0.033)。此研究顯示遠紅外線熱影像有助於記錄脛前黏液水腫，並且可能有助偵測早期脛前黏液水腫的發生。
另一研究收納了46個接受大劑量類固醇治療甲狀腺眼病變的病人，以遠紅外線熱影像觀察眼睛溫度的變化。在大劑量類固醇治療後眼睛溫度平均來說會下降，溫度下降的程度與治療前的眼睛溫度成正相關(p= 0.004)。此研究顯示遠紅外線熱影像的溫度測量有助於預測大劑量類固醇治療甲狀腺眼病變的效果。
在甲狀腺乳突癌方面，我們嘗試用電腦程式分析術前以細針穿刺取得的甲狀腺乳突癌細胞型態，共迴溯性地收納研究了142個乳突癌病人的癌細胞，多變項迴歸分析發現病人在10年內復發的可能性與核質比、細胞核面積變異度、腫瘤大小、和病人年齡有統計顯著相關。此研究顯示以型態分析程式分析細針穿刺取得的甲狀腺乳突癌細胞，有助於在術前預測病人的預後。
總之，根據目前初步的研究成果顯示：遠紅外線熱影像有助於記錄葛雷夫氏症脛前黏液水腫及預測大劑量類固醇治療眼病變的效果，型態分析程式分析有助於預測甲狀腺乳突癌的預後。希望將來有更深入的研究並實際運用在臨床上。

Dysfunction and anatomic abnormalities of the thyroid are among the most common diseases of the endocrine glands. On the aspect of thyroid dysfunction, Graves’ disease (GD) is the most common form of throtoxicosis. It is characterized by thyrotoxicosis and goiter. Patients may have ophthalmopathy and pretibial myxedema (PM). Currently, there is no satisfactory tool to record and investigate PM, and to describe the inflammatory status of Graves’ ophthalmopathy (GO). It limits the choice and development of therapy. As to the anatomic abnormality of the thyroid, papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Currently, prognostic evaluation tools can be performed only after surgery because they depend on the observation and records of operation and pathology reports. They are not helpful for the operation planning for the extent of thyroidectomy and lymph node dissection. This study aimed to solve these important clinical issues.
Digital infrared thermal imaging (DITI) detects surface temperature. We tried to appliy it to help observe and record GD complications. On the aspect of PM, eighty-seven GD patients with or without PM and 14 normal volunteers were recruited for observation of lower legs with DITI. DITI showed abnormally low focal temperature over PM lesions and in some GD patients without obvious PM. Thyrotropin receptor antibody level correlated positively and significantly with adjusted temperature difference between the center of temperature defect and the surrounding skin (p=0.033). We demonstrated that DITI is helpful in recording and may be a useful tool to detect early changes of PM.
On the aspect of GO, forty-six patients with GO receiving intravenously methylprednisolone pulse therapy (MPT) were included for observation of the eye temperature with DITI. Local temperatures of the eyes decreased after MPT. Temperature difference (△T) significantly negative-correlated with basal mean temperature (MT) (p= 0.004). We demonstrated that DITI is valuable in the prediction of prognosis after MPT.
As to PTC, we tried to analyze cytologic features with computerized morphometry (CM) to help predicting prognosis preoperatively. Cytologic features of 142 patients with usual-type PTC were studied with CM retrospectively. Multivariate logistic analysis indicated that nucleus-to-cell ratio, variation of nuclear area, tumor size, and patients’ age were significantly related to cancer recurrence in 10 years. We demonstrated that CM helped to predict prognosis preoperatively.
In summary, according to current preliminary reports, DITI is useful in recording PM and predicting the prognosis of GO after MPT; and CM is useful in predicting the prognosis of PTC. Further large scale studies are necessary to help applying these methods clinically.

口試委員審定書............................................1
中文摘要..................................................5
Abstract..................................................7

Chapter 1: Introduction
1.1 Background .....................................11
1.1.1 Gravse'' Dermopathy..............................12
1.1.2 Graves'' Orbitopathy.............................13
1.1.3 Papillary Thyroid Cancer........................14
1.1.4 Digital Infrared Thermal Imaging................16
1.1.5 Computerized Morphometry........................17
1.2 Literature Review...............................18
1.2.1 The Application of Digital Infrared Thermal Imaging .................................................18
1.2.2 The Application of Computerized Morphometry.....18
1.3 Purpose.........................................19

Chapter 2: Materials and Methods
2.1 New Approaches to the Recording and Early Detection of Graves’ Dermopathy Using Digital Infrared Thermal Imaging..........................................21
2.2 New Approaches to the Prognositic Prediction of Methylprednisolone Pulse Therapy of Graves’ Orbitopathy Using Digital Infrared Thermal Imaging..................26
2.3 New Approaches to the Preoperative Prognositic Prediction of Papillary Thyroid Cancer Using Computerized Morphometry of Cytology Samples..........................31

Chapter 3: Results
3.1 Digital Infrared Thermal Imaging Helps to Record and Early Detect Graves’ Dermopathy.....................37
3.2 Digital Infrared Thermal Imaging Helps to Predict the Effect of Methylprednisolone Pulse Therapy of Graves’ Orbitopathy..............................................43
3.3 Computerized Morphometry of Cytology Samples Helps to Predict the Prognosis of Papillary Thyroid Cancer Preoperatively...........................................48

Chapter 4: Discussion
4.1 The Application of Digital Infrared Thermal Imaging in Recording and Early Detection of Graves’ Dermopathy...............................................56
4.2 The Application of Digital Infrared Thermal Imaging in Prognositic Prediction of Methylprednisolone Pulse Therapy of Graves’ Orbitopathy....................60
4.3 The Application of Computerized Morphometry of Cytology Samples in the Preoperative Prognositic Prediction of Papillary Thyroid Cancer..............................63

Chapter 5: Conclusion
5.1 Digital Infrared Thermal Imaging is Useful in Recording and Early Detection of Graves’ Dermopathy...............................................67
5.2 Digital Infrared Thermal Imaging is Useful in Predicting the Effect of Methylprednisolone Pulse Therapy of Graves’ Orbitopathy..................................68
5.3 Computerized Morphometry of Cytology Samples is Useful in Predicting the Prognosis of Papillary Thyroid Cancer Preoperatively....................................68

Chapter 6: Future Works..................................70

Reference ..............................................71

1.Greenspan FS. The thyroid gland. In: Greenspan FS, Gardner DG, eds. Basic and clinical endocrinology. 6 ed. New York: McGraw-Hill Companies; 2004:215-94.
2.Parry CH. Disease of the heart. In: Collections from the Unpublished Writings. London: Underwoods; 1825:111-25.
3.Tunbridge WM, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977;7:481-93.
4.Jiang LJ, Ng EY, Yeo AC, et al. A perspective on medical infrared imaging. J Med Eng Technol 2005;29:257-67.
5.Jones BF. A reappraisal of the use of infrared thermal image analysis in medicine. IEEE Trans Med Imaging 1998;17:1019-27.
6.Wang SL, Wu MT, Yang SF, Chan HM, Chai CY. Computerized nuclear morphometry in thyroid follicular neoplasms. Pathol Int 2005;55:703-6.
7.Lavie O, Maini I, Pilip A, et al. Computerized nuclear morphometry for the prediction of inguinal lymph nodes metastases in squamous cell carcinoma of the vulva. Int J Gynecol Cancer 2006;16:556-61.
8.Fatourechi V, Pajouhi M, Fransway AF. Dermopathy of Graves disease (pretibial myxedema). Review of 150 cases. Medicine (Baltimore) 1994;73:1-7.
9.Chang TC, Kao SC, Huang KM. Octreotide and Graves'' ophthalmopathy and pretibial myxoedema. BMJ 1992;304:158.
10.Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol 2005;6:295-309.
11.Rotman-Pikielny P, Brucker-Davis F, Turner ML, Sarlis NJ, Skarulis MC. Lack of effect of long-term octreotide therapy in severe thyroid-associated dermopathy. Thyroid 2003;13:465-70.
12.Schwartz KM, Fatourechi V, Ahmed DD, Pond GR. Dermopathy of Graves'' disease (pretibial myxedema): long-term outcome. J Clin Endocrinol Metab 2002;87:438-46.
13.Wartofsky L. Classification of eye changes of Graves'' disease. Thyroid 1992;2:235-6.
14.Werner SC. Classification of the eye changes of Graves'' disease. Am J Ophthalmol 1969;68:646-8.
15.Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves'' ophthalmopathy: a novel approach. Br J Ophthalmol 1989;73:639-44.
16.Hay ID. Papillary thyroid carcinoma. Endocrinol Metab Clin North Am 1990;19:545-76.
17.DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1990;71:414-24.
18.Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery 1993;114:1050-7; discussion 7-8.
19.Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987;102:1088-95.
20.Schlumberger MJ, Filetti S, Hey ID. Nontoxic goiter and thyroid neoplasia. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS, eds. Williams Textbook of Endocrinology. 10 ed. Philadelphia: Saunders; 2005:457-90.
21.Shah JP, Loree TR, Dharker D, Strong EW, Begg C, Vlamis V. Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 1992;164:658-61.
22.Simpson WJ, McKinney SE, Carruthers JS, Gospodarowicz MK, Sutcliffe SB, Panzarella T. Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients. Am J Med 1987;83:479-88.
23.Bononi M, Tocchi A, Cangemi V, et al. Lymph node dissection in papillary or follicular thyroid carcinoma. Anticancer Res 2004;24:2439-42.
24.Ley PB, Roberts JW, Symmonds RE, Jr., et al. Safety and efficacy of total thyroidectomy for differentiated thyroid carcinoma: a 20-year review. Am Surg 1993;59:110-4.
25.Mann B, Buhr HJ. Lymph node dissection in patients with differentiated thyroid carcinoma--who benefits? Langenbecks Arch Surg 1998;383:355-8.
26.Mazzaferri EL, Kloos RT. Clinical review 128: Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab 2001;86:1447-63.
27.Watkinson JC. The British Thyroid Association guidelines for the management of thyroid cancer in adults. Nucl Med Commun 2004;25:897-900.
28.Ito Y, Tomoda C, Uruno T, et al. Papillary microcarcinoma of the thyroid: how should it be treated? World J Surg 2004;28:1115-21.
29.Ito Y, Uruno T, Nakano K, et al. An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Thyroid 2003;13:381-7.
30.Lin JD, Chen ST, Chao TC, Hsueh C, Weng HF. Diagnosis and therapeutic strategy for papillary thyroid microcarcinoma. Arch Surg 2005;140:940-5.
31.Orsenigo E, Beretta E, Fiacco E, et al. Management of papillary microcarcinoma of the thyroid gland. Eur J Surg Oncol 2004;30:1104-6.
32.Sakorafas GH, Giotakis J, Stafyla V. Papillary thyroid microcarcinoma: a surgical perspective. Cancer Treat Rev 2005;31:423-38.
33.Shih SR, Li HY, Hsiao YL, Chang TC. Prognostic significance of cytologic features in fine-needle aspiration cytology samples of papillary thyroid carcinoma: preliminary report. Thyroid 2006;16:775-80.
34.Chang TC, Hsiao YL, Liao SL. Application of digital infrared thermal imaging in determining inflammatory state and follow-up effect of methylprednisolone pulse therapy in patients with Graves'' ophthalmopathy. Graefes Arch Clin Exp Ophthalmol 2008;246:45-9.
35.Shih SR, Li HY, Hsiao YL, Chang TC. The application of temperature measurement of the eyes by digital infrared thermal imaging as a prognostic factor of methylprednisolone pulse therapy for Graves'' ophthalmopathy. Acta Ophthalmol 2010;88:e154-9.
36.Singh SP, Ellyin F, Singh SK, Yoon B. Elephantiasis-like appearance of upper and lower extremities in Graves'' dermopathy. Am J Med Sci 1985;290:73-6.
37.Sun PC, Lin HD, Jao SH, Ku YC, Chan RC, Cheng CK. Relationship of skin temperature to sympathetic dysfunction in diabetic at-risk feet. Diabetes Res Clin Pract 2006;73:41-6.
38.Agnese DM. Advances in breast imaging. Surg Technol Int 2005;14:51-6.
39.Singh G, Bhinder HS. Comparison of noncontact infrared and remote sensor thermometry in normal and dry eye patients. Eur J Ophthalmol 2005;15:668-73.
40.Arora N, Martins D, Ruggerio D, et al. Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer. Am J Surg 2008;196:523-6.
41.Ikeguchi M, Sakatani T, Endo K, Makino M, Kaibara N. Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma. Cancer 1999;86:1944-51.
42.Ikeguchi M, Cai J, Oka S, et al. Nuclear profiles of cancer cells reveal the metastatic potential of gastric cancer. J Pathol 2000;192:19-25.
43.Ishikawa F, Saito N, Koda K, et al. Nuclear morphometric analysis of T2 lesions of the rectum--a simple, reproducible method for predicting malignancy potential. Am J Surg 2002;183:686-91.
44.Parada D, Farias RM, Garcia-Tamayo J. [Morphometric analysis of nuclear variations in normal and neoplastic mammary ductal cells]. Invest Clin 1999;40:233-44.
45.Karbowniczek M, Chosia M, Domagala W. Nuclear morphometry of MIB-1 positive and negative tumor cells in primary and metastatic malignant melanoma of the skin. Pol J Pathol 1999;50:235-41.
46.Kazanowska B, Jelen M, Reich A, Tarnawski W, Chybicka A. The role of nuclear morphometry in prediction of prognosis for rhabdomyosarcoma in children. Histopathology 2004;45:352-9.
47.Paraskevakou E, Kavantzas N, Pavlopoulos PM, Delibasis A, Yova D, Davaris P. Computerized nuclear morphometry of renal cell carcinomas. Gen Diagn Pathol 1996;142:101-4.
48.Kirillov V, Stebenyaeva E, Paplevka A, Demidchik E. A rapid method for diagnosing regional metastases of papillary thyroid cancer with morphometry. Microsc Res Tech 2006;69:721-8.
49.Kirillov VA, Stebenyaeva EE, Paplevka AA, Demidchik EP. Quantitative changes in thyroid lymphoid cells as a marker of malignancy. Anal Quant Cytol Histol 2005;27:101-10.
50.Nagashima T, Suzuki M, Oshida M, et al. Morphometry in the cytologic evaluation of thyroid follicular lesions. Cancer 1998;84:115-8.
51.Tseleni-Balafouta S, Kavantzas N, Paraskevakou H, Davaris P. Computerized morphometric study on fine needle aspirates of cellular follicular lesions of the thyroid. Anal Quant Cytol Histol 2000;22:323-6.
52.Chang TC, Huang KM, Hsiao YL, Tzeng SS, Kao SC. Relationships of orbital computed tomographic findings and activity scores to the prognosis of corticosteroid therapy in patients with Graves'' ophthalmopathy. Acta Ophthalmol Scand 1997;75:301-4.
53.Chang TC, Kou SH, Chen FW, et al. Cytopathology of thyroid cancer by fine needle aspiration with Liu''s stain. Taiwan Yi Xue Hui Za Zhi 1982;81:1404-12.
54.Riu CH. A new rapid method of staining thin blood film: first report. Taiwan Yi Xue Hui Za Zhi (J Formos Med Assoc) 1953;52:348-52.
55.Tsou MH, Lin HH, Ko JS. Riu''s stain and the cytologic diagnosis of thyroid fine-needle aspiration: a single cancer center experience. Diagn Cytopathol 1997;16:543-7.
56.Dinarello CAG, J.A. Fever and hyperthermia. In: Braunwald EH, S.L.; Fauci, A.S.; Kasper, D.L.; Longo, D.L.; Jameson, L.J., ed. Harrison'' principal of internal medicine. 15 ed. New York: McGraw-Hill Companies; 2001:191-4.
57.Salvi M, De Chiara F, Gardini E, et al. Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease. Eur J Endocrinol 1994;131:113-9.
58.Wortsman J, Dietrich J, Traycoff RB, Stone S. Preradial myxedema in thyroid disease. Arch Dermatol 1981;117:635-8.
59.Wright AL, Buxton PK, Menzies D. Pretibial myxedema localized to scar tissue. Int J Dermatol 1990;29:54-5.
60.Davies TFL, P.R. Thyrotoxicosis. In: William RHL, P.R., ed. Williams Textbook of Endocrinology. 10 ed. Philadelphia: Elsevier Science; 2003:374-422.
61.Simeonov R, Simeonova G. Computerized morphometry of mean nuclear diameter and nuclear roundness in canine mammary gland tumors on cytologic smears. Vet Clin Pathol 2006;35:88-90.
62.Tseleni S, Kavantzas N, Yova D, et al. Findings of computerized nuclear morphometry of papillary thyroid carcinoma in correlation with the age of the patients. Gen Diagn Pathol 1997;143:23-7.
63.Nagashima T, Sakakibara M, Nakatani Y, Miyazaki M. Preoperative cytologic morphometry may assist in predicting patient outcome after surgery in papillary thyroid cancer. Anal Quant Cytol Histol 2008;30:231-6.
64.Suzuki M, Oshida M, Nagashima T, Hashimoto H, Yagata H, Nakajima N. Quantitative morphometric analysis of fine needle aspirates of breast carcinoma. Breast Cancer 2001;8:138-45.
65.Rosai J. Papillary carcinoma. Monogr Pathol 1993:138-65.
66.Akslen LA, Myking AO, Salvesen H, Varhaug JE. Prognostic importance of various clinicopathological features in papillary thyroid carcinoma. Eur J Cancer 1992;29A:44-51.
67.De Vico G, Sfacteria A, Maiolino P, Mazzullo G. Comparison of nuclear morphometric parameters in cytologic smears and histologic sections of spontaneous canine tumors. Vet Clin Pathol 2002;31:16-8.
68.Ladekarl M. The influence of tissue processing on quantitative histopathology in breast cancer. J Microsc 1994;174:93-100.