垂体ACTH腺瘤经蝶术后复发相关因素分析—临床回顾及免疫组化研究
|
摘要
目的了解ACTH腺瘤所致的Cushing病患者经蝶手术后复发相关的临床因素,寻找其中能较好预测术后复发的临床指标。通过免疫组化比较增殖性及侵袭性指标在复发组及非复发组内表达差异性,寻找导致复发的肿瘤细胞学特性及分子表型,为进一步探讨机制提供理论依据。
方法在1990至2004间全部我院经蝶手术地库欣病患者中,随机选择诊断明确,入院前未接受过与库欣病相关的手术,术后经病理证实为垂体ACTH腺瘤且病历及随访资料完整的60例患者。依相应标准,分为复发及非复发组。回顾性分析组间性别、发病年龄、病程、肿瘤平均径线、术前及术后内分泌水平及手术情况等临床因素,同时运用免疫组化技术,分析Ki-67,基质金属蛋白酶9、垂体腺瘤转化基因及高迁移率蛋白A2在两组腺瘤组织中表达水平的差异。
结果临床因素方面,较多的术中出血(通常>400ml)及术后血F值偏高可以作为库欣病经蝶手术后复发的较为可靠的预测因素,以术后一周早上8点血F值3.65ug/dl作为界值此判断术后复发的敏感性为75%,特异性为66.7%。此外,女性,术前影像学不明确和垂体平均径线大于等于1cm可能也是复发危险因素之一。四个侵袭及增殖指标中,基质金属蛋白酶9在复发组中表达显著增高(P=0.022),且表达量与复发间隔有极显著相关性(P=0.007,相关系数=-0.354),其余指标在两组间表达均无差异。
结论垂体ACTH腺瘤经蝶术后复发是个多因素影响的过程。其中术中减少不必要的出血有助于减少复发,术后血皮质醇水平偏高预示术后可能复发。高表达基质金属蛋白酶9的垂体ACTH腺瘤具有较高的侵袭性,术中难以完全切净致使这部分肿瘤更易复发,且复发间隔时间较短。对于有复发高危因素的患者应密切随访。
Objective To investigate the recurrence-related clinical factors in patients with adrenocorticotropic pituitary adenoma-induced Cushing's disease who underwent transsphenoidal surgery and to find out the most predictive one(s) among them. We compared the expressions of several proliferative and invasive biomarkers by Immunohistochemistry to find out the recurrence-related cellular characteristic and molecular phenotype, which facilitates exploring its underlying mechanism.
Method We randomly reviewed60patients with definite-diagnosed Cushing's disease who had confirmed adrenocorticotropic pituitary adenoma after transsphenoidal surgery from1990to2004in our hospital. All of them didn't receive any relevant treatment before admission and had long-term follow-up. They were assigned to recurrence or non-recurrence group according to relevant standards. We retrospectively analysed the gender, age, course, mean diameter of tumor, preoperative and postoperative hormone levels and the conditions during surgery. Meanwhile, we mensurated the different expressions of Ki-67, matrix metalloproteinase9, pituitary tumor transforming gene and high mobility group AT-hook2by Immunohistochemistry in two groups.
Result Among clinical factors, high-volume blood loss during surgery (generally>400ml) and high postoperative cortisol level were most predictive indices. The postoperative cortisol level over3.65ug/dl predict recurrence with75%sensitivity and66.7%specificity. Moreover, female, mean diameter larger or equal to1cm and ambiguous preoperative MRI also seemed to be related to recurrence. The expression of matrix metalloproteinase9was significantly high in recurrence group (P=0.022) and was strongly related to the interval of recurrence (P=0.007, CC=-0.354). The other three biomarkers showed no statistic difference in two groups.
Conclusion The recurrence of adrenocorticotropic pituitary adenoma after transsphenoidal surgery was influenced by multiple factors. Minimize the blood loss during surgery probably prevent recurrence. High postoperative cortisol level probably predicts recurrence. Tumors with high expression of matrix metalloproteinase9were more invasive, which means more difficult to be cut off completely. They were vulnerable to recurrence with shorter disease-free interval. The patients who had related risk factors should be followed-up closely.
方法在1990至2004间全部我院经蝶手术地库欣病患者中,随机选择诊断明确,入院前未接受过与库欣病相关的手术,术后经病理证实为垂体ACTH腺瘤且病历及随访资料完整的60例患者。依相应标准,分为复发及非复发组。回顾性分析组间性别、发病年龄、病程、肿瘤平均径线、术前及术后内分泌水平及手术情况等临床因素,同时运用免疫组化技术,分析Ki-67,基质金属蛋白酶9、垂体腺瘤转化基因及高迁移率蛋白A2在两组腺瘤组织中表达水平的差异。
结果临床因素方面,较多的术中出血(通常>400ml)及术后血F值偏高可以作为库欣病经蝶手术后复发的较为可靠的预测因素,以术后一周早上8点血F值3.65ug/dl作为界值此判断术后复发的敏感性为75%,特异性为66.7%。此外,女性,术前影像学不明确和垂体平均径线大于等于1cm可能也是复发危险因素之一。四个侵袭及增殖指标中,基质金属蛋白酶9在复发组中表达显著增高(P=0.022),且表达量与复发间隔有极显著相关性(P=0.007,相关系数=-0.354),其余指标在两组间表达均无差异。
结论垂体ACTH腺瘤经蝶术后复发是个多因素影响的过程。其中术中减少不必要的出血有助于减少复发,术后血皮质醇水平偏高预示术后可能复发。高表达基质金属蛋白酶9的垂体ACTH腺瘤具有较高的侵袭性,术中难以完全切净致使这部分肿瘤更易复发,且复发间隔时间较短。对于有复发高危因素的患者应密切随访。
Objective To investigate the recurrence-related clinical factors in patients with adrenocorticotropic pituitary adenoma-induced Cushing's disease who underwent transsphenoidal surgery and to find out the most predictive one(s) among them. We compared the expressions of several proliferative and invasive biomarkers by Immunohistochemistry to find out the recurrence-related cellular characteristic and molecular phenotype, which facilitates exploring its underlying mechanism.
Method We randomly reviewed60patients with definite-diagnosed Cushing's disease who had confirmed adrenocorticotropic pituitary adenoma after transsphenoidal surgery from1990to2004in our hospital. All of them didn't receive any relevant treatment before admission and had long-term follow-up. They were assigned to recurrence or non-recurrence group according to relevant standards. We retrospectively analysed the gender, age, course, mean diameter of tumor, preoperative and postoperative hormone levels and the conditions during surgery. Meanwhile, we mensurated the different expressions of Ki-67, matrix metalloproteinase9, pituitary tumor transforming gene and high mobility group AT-hook2by Immunohistochemistry in two groups.
Result Among clinical factors, high-volume blood loss during surgery (generally>400ml) and high postoperative cortisol level were most predictive indices. The postoperative cortisol level over3.65ug/dl predict recurrence with75%sensitivity and66.7%specificity. Moreover, female, mean diameter larger or equal to1cm and ambiguous preoperative MRI also seemed to be related to recurrence. The expression of matrix metalloproteinase9was significantly high in recurrence group (P=0.022) and was strongly related to the interval of recurrence (P=0.007, CC=-0.354). The other three biomarkers showed no statistic difference in two groups.
Conclusion The recurrence of adrenocorticotropic pituitary adenoma after transsphenoidal surgery was influenced by multiple factors. Minimize the blood loss during surgery probably prevent recurrence. High postoperative cortisol level probably predicts recurrence. Tumors with high expression of matrix metalloproteinase9were more invasive, which means more difficult to be cut off completely. They were vulnerable to recurrence with shorter disease-free interval. The patients who had related risk factors should be followed-up closely.
引文
1. Bademci, G., Pitfalls in the management of Cushing's disease. J Clin Neurosci, 2007.14(5):p.401-8; discussion 409.
2. H, C., The basophil adenomas of pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932.50:p.137-195.
3. Etxabe, J. and J.A. Vazquez, Morbidity and mortality in Cushing's disease:an epidemiological approach. Clin Endocrinol (Oxf),1994.40(4):p.479-84.
4. Rhoton, A.L., Jr., Operative techniques and instrumentation for neurosurgery. Neurosurgery,2003.53(4):p.907-34; discussion 934.
5. Jane, J.A., Jr., et al., Pituitary surgery:transsphenoidal approach. Neurosurgery, 2002.51(2):p.435-42; discussion 442-4.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg, 1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p.967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease:initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005.34(2): p.459-78, xi.
14. Patil, C.G., et al., Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab,2008.93(2):p.358-62.
15. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
16. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas:an outcome study using modern remission criteria. J Clin Endocrinol Metab,2001. 86(9):p.4072-7.
17. Barker, F.G.,2nd, A. Klibanski, and B. Swearingen, Transsphenoidal surgery for pituitary tumors in the United States,1996-2000:mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab,2003.88(10):p. 4709-19.
18. Avgerinos, P.C., et al., The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome. J Clin Endocrinol Metab,1987.65(5):p.906-13.
19. Pieters, G.F., et al., Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing's disease. J Clin Endocrinol Metab,1989.69(6):p. 1122-6.
20. Toms, G.C., et al., Predicting relapse after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,1993.76(2):p.291-4.
21. Trainer, P.J., et al., Transsphenoidal resection in Cushing's disease:undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf), 1993.38(1):p.73-8.
22. Knappe, U.J. and D.K. Ludecke, Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl,1996.65:p. 31-4.
23. Arnott, R.D., et al., A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease:prediction of outcome. Acta Endocrinol (Copenh),1990.123(4):p.423-30.
24. Esposito, F., et al., Clinical review:Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,2006.91(1):p.7-13.
25. Yap, L.B., et al., Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease:a single centre audit. Clin Endocrinol (Oxf),2002.56(1):p.25-31.
26. Invitti, C., et al., Diagnosis and management of Cushing's syndrome:results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab,1999.84(2):p.440-8.
27. McCance, D.R., et al., Assessment of endocrine function after transsphenoidal surgery for Cushing's disease. Clin Endocrinol (Oxf),1993.38(1):p.79-86.
28. Simmons, N.E., et al., Serum cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg,2001.95(1):p.1-8.
29. Valero, R., et al., The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease. Eur J Endocrinol,2004.151(6):p.727-33.
30. Ludecke, D.K., et al., Cushing's disease:a surgical view. J Neurooncol,2001.54(2): p.151-66.
31. Hall, W.A., et al., Pituitary magnetic resonance imaging in normal human volunteers:occult adenomas in the general population. Ann Intern Med,1994. 120(10):p.817-20.
32. Chee, G.H., et al., Transsphenoidal pituitary surgery in Cushing's disease:can we predict outcome? Clin Endocrinol (Oxf),2001.54(5):p.617-26.
33. Salenave, S., et al., Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas. J Clin Endocrinol Metab,2004.89(7):p.3371-6.
34. Giovanelli, M., M. Losa, and P. Mortini, Surgical therapy of pituitary adenomas. Metabolism,1996.45(8 Suppl 1):p.115-6.
35. Cannavo, S., et al., Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas. Eur J Endocrinol,2003.149(3):p. 195-200.
36. Blevins, L.S., Jr., et al., Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab, 1998.83(1):p.63-7.
37. Boggan, J.E., J.B. Tyrrell, and C.B. Wilson, Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases. J Neurosurg,1983.59(2): p.195-200.
38. Hoybye, C., et al., Transsphenoidal surgery in Cushing disease:10 years of experience in 34 consecutive cases. J Neurosurg,2004.100(4):p.634-8.
39. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
40. Dickstein, G., E. Arad, and C. Shechner, Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma. Arch Intern Med,1997.157(20):p.2377-80.
41. Robert, F. and J. Hardy, Cushing's disease:a correlation of radiological, surgical and pathological findings with therapeutic results. Pathol Res Pract,1991.187(5): p.617-21.
42. Leinung, M.C., et al., Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood. J Clin Endocrinol Metab,1995.80(8): p.2475-9.
43. Magiakou, M.A., et al., Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med,1994.331(10):p.629-36.
44. Sonino, N., et al., Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab,1996.81(7):p.2647-52.
45. Sheehan, J.M., et al., Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor. Neurosurgery,2000.47(1):p. 33-6; discussion 37-9.
46.郭兰君,任祖渊,薛辉,常规病理检查未发现垂体腺瘤的Cushing病的临床与病理研究.中华神经外科杂志,1993(9)：p.144-6.
47. Thomale, U.W., J.F. Stover, and A.W. Unterberg, The use of neuronavigation in transnasal transsphenoidal pituitary surgery. Zentralbl Neurochir,2005.66(3):p. 126-32; discussion 132.
48. Fahlbusch, R. and K. Thapar, New developments in pituitary surgical techniques. Baillieres Best Pract Res Clin Endocrinol Metab,1999.13(3):p.471-84.
49. Jho, H.D., Endoscopic transsphenoidal surgery. J Neurooncol,2001.54(2):p. 187-95.
50. Asthagiri, A.R., E.R. Laws, Jr., and J.A. Jane, Jr., Image guidance in pituitary surgery. Front Horm Res,2006.34:p.46-63.
51. Watson, J.C., et al., Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg,1998.89(6):p.927-32.
52. Ram, Z., B. Bruck, and M. Hadani, Ultrasound in pituitary tumor surgery. Pituitary, 1999.2(2):p.133-8.
53. Kurosaki, M., et al., The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma. Acta Neurochir (Wien),2000.142(8): p.865-70.
1. Monson, J.P., The epidemiology of endocrine tumours. Endocr Relat Cancer,2000. 7(1):p.29-36.
2. Ezzat, S., et al., The prevalence of pituitary adenomas:a systematic review. Cancer,2004.101(3):p.613-9.
3. Tomita, T. and E. Gates, Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy. Am J Clin Pathol,1999.111(6):p.817-25.
4. Chong, B.W., et al., Pituitary gland MR:a comparative study of healthy volunteers and patients with microadenomas. AJNR Am J Neuroradiol,1994.15(4):p.675-9.
5. Trouillas, J., [Pathology and pathogenesis of pituitary corticotroph adenoma]. Neurochirurgie,2002.48(2-3 Pt 2):p.149-62.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg, 1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p.967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease:initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005.34(2): p.459-78, xi.
14. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
15. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas:an outcome study using modern remission criteria. J Clin Endocrinol Metab,2001. 86(9):p.4072-7.
16. Shibuya, M., et al., Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts. Acta Neuropathol,1992.84(2):p.178-83.
17. Hsu, D.W., et al., Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg,1993.78(5):p.753-61.
18. Vogelstein, B., et al., Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res,1987.47(18):p.4806-13.
19. Mashal, R.D., S.C. Lester, and J. Sklar, Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin-embedded tissue. Cancer Res,1993.53(19): p.4676-9.
20. Thomas, G.A., D. Williams, and E.D. Williams, The demonstration of tissue clonality by X-linked enzyme histochemistry. J Pathol,1988.155(2):p.101-8.
21. Prchal, J.T., et al., Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism. J Exp Med,1996.183(2):p.561-7.
22. Herman, V., et al., Clonal origin of pituitary adenomas. J Clin Endocrinol Metab, 1990.71(6):p.1427-33.
23. Dahia, P.L. and A.B. Grossman, The molecular pathogenesis of corticotroph tumors. Endocr Rev,1999.20(2):p.136-55.
24. Gejman, R., B. Swearingen, and E.T. Hedley-Whyte, Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Hum Pathol,2008.39(5):p.758-66.
25. Zhang, X., et al., Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol,1999.13(1):p.156-66.
26. Zhang, X., et al., Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab,1999.84(2):p.761-7.
27. McCabe, C.J., et al., Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas:relationships to clinical tumour behaviour. Clin Endocrinol (Oxf),2003.58(2):p.141-50.
28. Filippella, M., et al., Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas:a clinical and immunohistochemical study. Clin Endocrinol (Oxf),2006. 65(4):p.536-43.
29. Malik, M.T. and S.S. Kakar, Regulation of angiogenesis and invasion by human Pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Mol Cancer,2006.5:p.61.
30. Turner, H.E., et al., Role of matrix metalloproteinase 9 in pituitary tumor behavior. J Clin Endocrinol Metab,2000.85(8):p.2931-5.
31. Knappe, U.J., et al., Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue. Acta Neuropathol, 2003.106(5):p.471-8.
32. Koutroulis, I., A. Zarros, and S. Theocharis, The role of matrix metalloproteinases in the pathophysiology and progression of human nervous system malignancies: a chance for the development of targeted therapeutic approaches? Expert Opin Ther Targets,2008.12(12):p.1577-86.
33. Reeves, R. and M.S. Nissen, The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem,1990.265(15):p.8573-82.
34. Thanos, D. and T. Maniatis, The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell,1992. 71(5):p.777-89.
35. Thanos, D., W. Du, and T. Maniatis, The high mobility group protein HMG I(Y) is an essential structural component of a virus-inducible enhancer complex. Cold Spring Harb Symp Quant Biol,1993.58:p.73-81.
36. Zhou, X., et al., Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature,1995.376(6543):p.771-4.
37. Chiappetta, G., et al., High level expression of the HMGI (Y) gene during embryonic development. Oncogene,1996.13(11):p.2439-46.
38. Qian, Z.R., et al., Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. Mod Pathol, 2009.22(3):p.431-41.
39. Honegger, J., et al., Expression of Ki-67 antigen in nonfunctioning pituitary adenomas:correlation with growth velocity and invasiveness. J Neurosurg,2003. 99(4):p.674-9.
40. Widhalm, G., et al., Residual nonfunctioning pituitary adenomas:prognostic value of MIB-1 labeling index for tumor progression. J Neurosurg,2008.
41. Daita, G., et al., Cavernous sinus invasion by pituitary adenomas--relationship between magnetic resonance imaging findings and histologically verified dural invasion. Neurol Med Chir (Tokyo),1995.35(1):p.17-21.
42. Dickerman, R.D. and E.H. Oldfield, Basis of persistent and recurrent Cushing disease:an analysis of findings at repeated pituitary surgery. J Neurosurg,2002. 97(6):p.1343-9.
43. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
1. Bademci, G., Pitfalls in the management of Cushing's disease. J Clin Neurosci, 2007.14(5):p.401-8; discussion 409.
2. H, C., The basophil adenomas of pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932.50:p.137-195.
3. Etxabe, J. and J.A. Vazquez, Morbidity and mortality in Cushing's disease:an epidemiological approach. Clin Endocrinol (Oxf),1994.40(4):p.479-84.
4. Rhoton, A.L., Jr., Operative techniques and instrumentation for neurosurgery. Neurosurgery,2003.53(4):p.907-34; discussion 934.
5. Jane, J.A., Jr., et al., Pituitary surgery:transsphenoidal approach. Neurosurgery,2002.51(2):p.435-42; discussion 442-4.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg,1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p. 967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005. 34(2):p.459-78, xi.
14. Patil, C.G., et al., Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab,2008.93(2):p.358-62.
15. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
16. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab, 2001.86(9):p.4072-7.
17. Robert, F. and J. Hardy, Cushing's disease:a correlation of radiological, surgical and pathological findings with therapeutic results. Pathol Res Pract, 1991.187(5):p.617-21.
18. Leinung, M.C., et al., Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood. J Clin Endocrinol Metab,1995. 80(8):p.2475-9.
19. Magiakou, M.A., et al., Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med,1994.331(10):p.629-36.
20. Ludecke, D.K., et al., Cushing's disease:a surgical view. J Neurooncol,2001. 54(2):p.151-66.
21. Hall, W.A., et al., Pituitary magnetic resonance imaging in normal human volunteers:occult adenomas in the general population. Ann Intern Med,1994. 120(10):p.817-20.
22. Barrou, Z., et al., [Magnetic resonance imaging in Cushing disease. Prediction of surgical results]. Presse Med,1997.26(1):p.7-11.
23. Chee, G.H., et al., Transsphenoidal pituitary surgery in Cushing's disease:can we predict outcome? Clin Endocrinol (Oxf),2001.54(5):p.617-26.
24. Salenave, S., et al., Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas. J Clin Endocrinol Metab,2004.89(7):p.3371-6.
25. Cannavo, S., et al., Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas. Eur J Endocrinol,2003.149(3):p. 195-200.
26. Pieters, G.F., et al., Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing's disease. J Clin Endocrinol Metab,1989.69(6):p. 1122-6.
27. Barker, F.G.,2nd, A. Klibanski, and B. Swearingen, Transsphenoidal surgery for pituitary tumors in the United States,1996-2000:mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab,2003.88(10): p.4709-19.
28. Thomale, U.W., J.F. Stover, and A.W. Unterberg, The use of neuronavigation in transnasal transsphenoidal pituitary surgery. Zentralbl Neurochir,2005.66(3): p.126-32; discussion 132.
29. Fahlbusch, R. and K. Thapar, New developments in pituitary surgical techniques. Baillieres Best Pract Res Clin Endocrinol Metab,1999.13(3):p. 471-84.
30. Jho, H.D., Endoscopic transsphenoidal surgery. J Neurooncol,2001.54(2):p. 187-95.
31. Asthagiri, A.R., E.R. Laws, Jr., and J.A. Jane, Jr., Image guidance in pituitary surgery. Front Horm Res,2006.34:p.46-63.
32. Watson, J.C., et al., Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg,1998.89(6):p.927-32.
33. Ram, Z., B. Bruck, and M. Hadani, Ultrasound in pituitary tumor surgery. Pituitary,1999.2(2):p.133-8.
34. Kurosaki, M., et al., The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma. Acta Neurochir (Wien),2000.142(8):p.865-70.
35. Sheehan, J.M., et al., Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor. Neurosurgery,2000.47(1): p.33-6; discussion 37-9.
36. Sonino, N., et al., Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab,1996.81(7):p.2647-52.
37.郭兰君,任祖渊,薛辉,常规病理检查未发现垂体腺瘤的Cushing病的临床与病理研究.中华神经外科杂志,1993(9)：p.144-6.
38. Avgerinos, P.C., et al., The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome. J Clin Endocrinol Metab,1987.65(5):p.906-13.
39. Toms, G.C., et al., Predicting relapse after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,1993.76(2):p.291-4.
40. Trainer, P.J., et al., Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf),1993.38(1):p.73-8.
41. Knappe, U.J. and D.K. Ludecke, Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl,1996.65: p.31-4.
42. Arnott, R.D., et al., A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease:prediction of outcome. Acta Endocrinol (Copenh),1990.123(4):p.423-30.
43. Esposito, F., et al., Clinical review:Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,2006.91(1):p.7-13.
44. Yap, L.B., et al., Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease:a single centre audit. Clin Endocrinol (Oxf),2002.56(1):p.25-31.
45. Invitti, C., et al., Diagnosis and management of Cushing's syndrome:results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab,1999.84(2):p.440-8.
46. Valero, R., et al., The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease. Eur J Endocrinol,2004.151(6):p. 727-33.
47. Vignati, F., M.E. Berselli, and P. Loi, Early postoperative evaluation in patients with Cushing's disease:usefulness of ovine corticotropin-releasing hormone test in the prediction of recurrence of disease. Eur J Endocrinol,1994.130(3): p.235-41.
48. Giovanelli, M., M. Losa, and P. Mortini, Surgical therapy of pituitary adenomas. Metabolism,1996.45(8 Suppl 1):p.115-6.
49. Boggan, J.E., J.B. Tyrrell, and C.B. Wilson, Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases. J Neurosurg,1983. 59(2):p.195-200.
50. Blevins, L.S., Jr., et al., Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab,1998.83(1):p.63-7.
51. Vogelstein, B., et al., Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res,1987.47(18):p.4806-13.
52. Mashal, R.D., S.C. Lester, and J. Sklar, Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin-embedded tissue. Cancer Res,1993.53(19):p.4676-9.
53. Thomas, G.A., D. Williams, and E.D. Williams, The demonstration of tissue clonality by X-linked enzyme histochemistry. J Pathol,1988.155(2):p.101-8.
54. Prchal, J.T., et al., Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism. J Exp Med,1996.183(2):p. 561-7.
55. Herman, V., et al., Clonal origin of pituitary adenomas. J Clin Endocrinol Metab,1990.71(6):p.1427-33.
56. Dahia, P.L. and A.B. Grossman, The molecular pathogenesis of corticotroph tumors. Endocr Rev,1999.20(2):p.136-55.
57. Solcia E, K.G., Sobin LH., Histological typing of endocrine tumors 2000, Berlin: Springer.1-149.
58. Daita, G., et al., Cavernous sinus invasion by pituitary adenomas--relationship between magnetic resonance imaging findings and histologically verified dural invasion. Neurol Med Chir (Tokyo),1995.35(1):p.17-21.
59. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
60. Dickstein, G., E. Arad, and C. Shechner, Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma. Arch Intern Med,1997.157(20):p.2377-80.
61. Nagesser, S.K., et al., Long-term results of total adrenalectomy for Cushing's disease. World J Surg,2000.24(1):p.108-13.
2. H, C., The basophil adenomas of pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932.50:p.137-195.
3. Etxabe, J. and J.A. Vazquez, Morbidity and mortality in Cushing's disease:an epidemiological approach. Clin Endocrinol (Oxf),1994.40(4):p.479-84.
4. Rhoton, A.L., Jr., Operative techniques and instrumentation for neurosurgery. Neurosurgery,2003.53(4):p.907-34; discussion 934.
5. Jane, J.A., Jr., et al., Pituitary surgery:transsphenoidal approach. Neurosurgery, 2002.51(2):p.435-42; discussion 442-4.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg, 1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p.967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease:initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005.34(2): p.459-78, xi.
14. Patil, C.G., et al., Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab,2008.93(2):p.358-62.
15. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
16. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas:an outcome study using modern remission criteria. J Clin Endocrinol Metab,2001. 86(9):p.4072-7.
17. Barker, F.G.,2nd, A. Klibanski, and B. Swearingen, Transsphenoidal surgery for pituitary tumors in the United States,1996-2000:mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab,2003.88(10):p. 4709-19.
18. Avgerinos, P.C., et al., The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome. J Clin Endocrinol Metab,1987.65(5):p.906-13.
19. Pieters, G.F., et al., Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing's disease. J Clin Endocrinol Metab,1989.69(6):p. 1122-6.
20. Toms, G.C., et al., Predicting relapse after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,1993.76(2):p.291-4.
21. Trainer, P.J., et al., Transsphenoidal resection in Cushing's disease:undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf), 1993.38(1):p.73-8.
22. Knappe, U.J. and D.K. Ludecke, Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl,1996.65:p. 31-4.
23. Arnott, R.D., et al., A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease:prediction of outcome. Acta Endocrinol (Copenh),1990.123(4):p.423-30.
24. Esposito, F., et al., Clinical review:Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,2006.91(1):p.7-13.
25. Yap, L.B., et al., Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease:a single centre audit. Clin Endocrinol (Oxf),2002.56(1):p.25-31.
26. Invitti, C., et al., Diagnosis and management of Cushing's syndrome:results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab,1999.84(2):p.440-8.
27. McCance, D.R., et al., Assessment of endocrine function after transsphenoidal surgery for Cushing's disease. Clin Endocrinol (Oxf),1993.38(1):p.79-86.
28. Simmons, N.E., et al., Serum cortisol response to transsphenoidal surgery for Cushing disease. J Neurosurg,2001.95(1):p.1-8.
29. Valero, R., et al., The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease. Eur J Endocrinol,2004.151(6):p.727-33.
30. Ludecke, D.K., et al., Cushing's disease:a surgical view. J Neurooncol,2001.54(2): p.151-66.
31. Hall, W.A., et al., Pituitary magnetic resonance imaging in normal human volunteers:occult adenomas in the general population. Ann Intern Med,1994. 120(10):p.817-20.
32. Chee, G.H., et al., Transsphenoidal pituitary surgery in Cushing's disease:can we predict outcome? Clin Endocrinol (Oxf),2001.54(5):p.617-26.
33. Salenave, S., et al., Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas. J Clin Endocrinol Metab,2004.89(7):p.3371-6.
34. Giovanelli, M., M. Losa, and P. Mortini, Surgical therapy of pituitary adenomas. Metabolism,1996.45(8 Suppl 1):p.115-6.
35. Cannavo, S., et al., Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas. Eur J Endocrinol,2003.149(3):p. 195-200.
36. Blevins, L.S., Jr., et al., Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab, 1998.83(1):p.63-7.
37. Boggan, J.E., J.B. Tyrrell, and C.B. Wilson, Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases. J Neurosurg,1983.59(2): p.195-200.
38. Hoybye, C., et al., Transsphenoidal surgery in Cushing disease:10 years of experience in 34 consecutive cases. J Neurosurg,2004.100(4):p.634-8.
39. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
40. Dickstein, G., E. Arad, and C. Shechner, Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma. Arch Intern Med,1997.157(20):p.2377-80.
41. Robert, F. and J. Hardy, Cushing's disease:a correlation of radiological, surgical and pathological findings with therapeutic results. Pathol Res Pract,1991.187(5): p.617-21.
42. Leinung, M.C., et al., Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood. J Clin Endocrinol Metab,1995.80(8): p.2475-9.
43. Magiakou, M.A., et al., Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med,1994.331(10):p.629-36.
44. Sonino, N., et al., Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab,1996.81(7):p.2647-52.
45. Sheehan, J.M., et al., Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor. Neurosurgery,2000.47(1):p. 33-6; discussion 37-9.
46.郭兰君,任祖渊,薛辉,常规病理检查未发现垂体腺瘤的Cushing病的临床与病理研究.中华神经外科杂志,1993(9)：p.144-6.
47. Thomale, U.W., J.F. Stover, and A.W. Unterberg, The use of neuronavigation in transnasal transsphenoidal pituitary surgery. Zentralbl Neurochir,2005.66(3):p. 126-32; discussion 132.
48. Fahlbusch, R. and K. Thapar, New developments in pituitary surgical techniques. Baillieres Best Pract Res Clin Endocrinol Metab,1999.13(3):p.471-84.
49. Jho, H.D., Endoscopic transsphenoidal surgery. J Neurooncol,2001.54(2):p. 187-95.
50. Asthagiri, A.R., E.R. Laws, Jr., and J.A. Jane, Jr., Image guidance in pituitary surgery. Front Horm Res,2006.34:p.46-63.
51. Watson, J.C., et al., Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg,1998.89(6):p.927-32.
52. Ram, Z., B. Bruck, and M. Hadani, Ultrasound in pituitary tumor surgery. Pituitary, 1999.2(2):p.133-8.
53. Kurosaki, M., et al., The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma. Acta Neurochir (Wien),2000.142(8): p.865-70.
1. Monson, J.P., The epidemiology of endocrine tumours. Endocr Relat Cancer,2000. 7(1):p.29-36.
2. Ezzat, S., et al., The prevalence of pituitary adenomas:a systematic review. Cancer,2004.101(3):p.613-9.
3. Tomita, T. and E. Gates, Pituitary adenomas and granular cell tumors. Incidence, cell type, and location of tumor in 100 pituitary glands at autopsy. Am J Clin Pathol,1999.111(6):p.817-25.
4. Chong, B.W., et al., Pituitary gland MR:a comparative study of healthy volunteers and patients with microadenomas. AJNR Am J Neuroradiol,1994.15(4):p.675-9.
5. Trouillas, J., [Pathology and pathogenesis of pituitary corticotroph adenoma]. Neurochirurgie,2002.48(2-3 Pt 2):p.149-62.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg, 1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p.967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease:initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005.34(2): p.459-78, xi.
14. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
15. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas:an outcome study using modern remission criteria. J Clin Endocrinol Metab,2001. 86(9):p.4072-7.
16. Shibuya, M., et al., Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts. Acta Neuropathol,1992.84(2):p.178-83.
17. Hsu, D.W., et al., Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg,1993.78(5):p.753-61.
18. Vogelstein, B., et al., Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res,1987.47(18):p.4806-13.
19. Mashal, R.D., S.C. Lester, and J. Sklar, Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin-embedded tissue. Cancer Res,1993.53(19): p.4676-9.
20. Thomas, G.A., D. Williams, and E.D. Williams, The demonstration of tissue clonality by X-linked enzyme histochemistry. J Pathol,1988.155(2):p.101-8.
21. Prchal, J.T., et al., Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism. J Exp Med,1996.183(2):p.561-7.
22. Herman, V., et al., Clonal origin of pituitary adenomas. J Clin Endocrinol Metab, 1990.71(6):p.1427-33.
23. Dahia, P.L. and A.B. Grossman, The molecular pathogenesis of corticotroph tumors. Endocr Rev,1999.20(2):p.136-55.
24. Gejman, R., B. Swearingen, and E.T. Hedley-Whyte, Role of Ki-67 proliferation index and p53 expression in predicting progression of pituitary adenomas. Hum Pathol,2008.39(5):p.758-66.
25. Zhang, X., et al., Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol,1999.13(1):p.156-66.
26. Zhang, X., et al., Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab,1999.84(2):p.761-7.
27. McCabe, C.J., et al., Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas:relationships to clinical tumour behaviour. Clin Endocrinol (Oxf),2003.58(2):p.141-50.
28. Filippella, M., et al., Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas:a clinical and immunohistochemical study. Clin Endocrinol (Oxf),2006. 65(4):p.536-43.
29. Malik, M.T. and S.S. Kakar, Regulation of angiogenesis and invasion by human Pituitary tumor transforming gene (PTTG) through increased expression and secretion of matrix metalloproteinase-2 (MMP-2). Mol Cancer,2006.5:p.61.
30. Turner, H.E., et al., Role of matrix metalloproteinase 9 in pituitary tumor behavior. J Clin Endocrinol Metab,2000.85(8):p.2931-5.
31. Knappe, U.J., et al., Expression of serine proteases and metalloproteinases in human pituitary adenomas and anterior pituitary lobe tissue. Acta Neuropathol, 2003.106(5):p.471-8.
32. Koutroulis, I., A. Zarros, and S. Theocharis, The role of matrix metalloproteinases in the pathophysiology and progression of human nervous system malignancies: a chance for the development of targeted therapeutic approaches? Expert Opin Ther Targets,2008.12(12):p.1577-86.
33. Reeves, R. and M.S. Nissen, The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem,1990.265(15):p.8573-82.
34. Thanos, D. and T. Maniatis, The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene. Cell,1992. 71(5):p.777-89.
35. Thanos, D., W. Du, and T. Maniatis, The high mobility group protein HMG I(Y) is an essential structural component of a virus-inducible enhancer complex. Cold Spring Harb Symp Quant Biol,1993.58:p.73-81.
36. Zhou, X., et al., Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Nature,1995.376(6543):p.771-4.
37. Chiappetta, G., et al., High level expression of the HMGI (Y) gene during embryonic development. Oncogene,1996.13(11):p.2439-46.
38. Qian, Z.R., et al., Overexpression of HMGA2 relates to reduction of the let-7 and its relationship to clinicopathological features in pituitary adenomas. Mod Pathol, 2009.22(3):p.431-41.
39. Honegger, J., et al., Expression of Ki-67 antigen in nonfunctioning pituitary adenomas:correlation with growth velocity and invasiveness. J Neurosurg,2003. 99(4):p.674-9.
40. Widhalm, G., et al., Residual nonfunctioning pituitary adenomas:prognostic value of MIB-1 labeling index for tumor progression. J Neurosurg,2008.
41. Daita, G., et al., Cavernous sinus invasion by pituitary adenomas--relationship between magnetic resonance imaging findings and histologically verified dural invasion. Neurol Med Chir (Tokyo),1995.35(1):p.17-21.
42. Dickerman, R.D. and E.H. Oldfield, Basis of persistent and recurrent Cushing disease:an analysis of findings at repeated pituitary surgery. J Neurosurg,2002. 97(6):p.1343-9.
43. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
1. Bademci, G., Pitfalls in the management of Cushing's disease. J Clin Neurosci, 2007.14(5):p.401-8; discussion 409.
2. H, C., The basophil adenomas of pituitary body and their clinical manifestations. Bull Johns Hopkins Hosp 1932.50:p.137-195.
3. Etxabe, J. and J.A. Vazquez, Morbidity and mortality in Cushing's disease:an epidemiological approach. Clin Endocrinol (Oxf),1994.40(4):p.479-84.
4. Rhoton, A.L., Jr., Operative techniques and instrumentation for neurosurgery. Neurosurgery,2003.53(4):p.907-34; discussion 934.
5. Jane, J.A., Jr., et al., Pituitary surgery:transsphenoidal approach. Neurosurgery,2002.51(2):p.435-42; discussion 442-4.
6. Ram, Z., et al., Early repeat surgery for persistent Cushing's disease. J Neurosurg,1994.80(1):p.37-45.
7. Bochicchio, D., M. Losa, and M. Buchfelder, Factors influencing the immediate and late outcome of Cushing's disease treated by transsphenoidal surgery:a retrospective study by the European Cushing's Disease Survey Group. J Clin Endocrinol Metab,1995.80(11):p.3114-20.
8. Rees, D.A., et al., Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission. Clin Endocrinol (Oxf),2002.56(4):p.541-51.
9. Chen, J.C., et al., Transsphenoidal microsurgical treatment of Cushing disease: postoperative assessment of surgical efficacy by application of an overnight low-dose dexamethasone suppression test. J Neurosurg,2003.98(5):p. 967-73.
10. Oldfeld, E.H., Cushing disease. J Neurosurg,2003.98(5):p.948-51; discussion 951.
11. Hammer, G.D., et al., Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. J Clin Endocrinol Metab,2004.89(12):p. 6348-57.
12. Atkinson, A.B., et al., Long-term remission rates after pituitary surgery for Cushing's disease:the need for long-term surveillance. Clin Endocrinol (Oxf), 2005.63(5):p.549-59.
13. Utz, A.L., B. Swearingen, and B.M. Biller, Pituitary surgery and postoperative management in Cushing's disease. Endocrinol Metab Clin North Am,2005. 34(2):p.459-78, xi.
14. Patil, C.G., et al., Late recurrences of Cushing's disease after initial successful transsphenoidal surgery. J Clin Endocrinol Metab,2008.93(2):p.358-62.
15. Freda, P.U., S.L. Wardlaw, and K.D. Post, Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly. J Neurosurg,1998.89(3):p.353-8.
16. Kreutzer, J., et al., Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab, 2001.86(9):p.4072-7.
17. Robert, F. and J. Hardy, Cushing's disease:a correlation of radiological, surgical and pathological findings with therapeutic results. Pathol Res Pract, 1991.187(5):p.617-21.
18. Leinung, M.C., et al., Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood. J Clin Endocrinol Metab,1995. 80(8):p.2475-9.
19. Magiakou, M.A., et al., Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med,1994.331(10):p.629-36.
20. Ludecke, D.K., et al., Cushing's disease:a surgical view. J Neurooncol,2001. 54(2):p.151-66.
21. Hall, W.A., et al., Pituitary magnetic resonance imaging in normal human volunteers:occult adenomas in the general population. Ann Intern Med,1994. 120(10):p.817-20.
22. Barrou, Z., et al., [Magnetic resonance imaging in Cushing disease. Prediction of surgical results]. Presse Med,1997.26(1):p.7-11.
23. Chee, G.H., et al., Transsphenoidal pituitary surgery in Cushing's disease:can we predict outcome? Clin Endocrinol (Oxf),2001.54(5):p.617-26.
24. Salenave, S., et al., Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas. J Clin Endocrinol Metab,2004.89(7):p.3371-6.
25. Cannavo, S., et al., Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas. Eur J Endocrinol,2003.149(3):p. 195-200.
26. Pieters, G.F., et al., Predictive factors for initial cure and relapse rate after pituitary surgery for Cushing's disease. J Clin Endocrinol Metab,1989.69(6):p. 1122-6.
27. Barker, F.G.,2nd, A. Klibanski, and B. Swearingen, Transsphenoidal surgery for pituitary tumors in the United States,1996-2000:mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab,2003.88(10): p.4709-19.
28. Thomale, U.W., J.F. Stover, and A.W. Unterberg, The use of neuronavigation in transnasal transsphenoidal pituitary surgery. Zentralbl Neurochir,2005.66(3): p.126-32; discussion 132.
29. Fahlbusch, R. and K. Thapar, New developments in pituitary surgical techniques. Baillieres Best Pract Res Clin Endocrinol Metab,1999.13(3):p. 471-84.
30. Jho, H.D., Endoscopic transsphenoidal surgery. J Neurooncol,2001.54(2):p. 187-95.
31. Asthagiri, A.R., E.R. Laws, Jr., and J.A. Jane, Jr., Image guidance in pituitary surgery. Front Horm Res,2006.34:p.46-63.
32. Watson, J.C., et al., Localization of pituitary adenomas by using intraoperative ultrasound in patients with Cushing's disease and no demonstrable pituitary tumor on magnetic resonance imaging. J Neurosurg,1998.89(6):p.927-32.
33. Ram, Z., B. Bruck, and M. Hadani, Ultrasound in pituitary tumor surgery. Pituitary,1999.2(2):p.133-8.
34. Kurosaki, M., et al., The value of intraoperative cytology during transsphenoidal surgery for ACTH-secreting microadenoma. Acta Neurochir (Wien),2000.142(8):p.865-70.
35. Sheehan, J.M., et al., Results of transsphenoidal surgery for Cushing's disease in patients with no histologically confirmed tumor. Neurosurgery,2000.47(1): p.33-6; discussion 37-9.
36. Sonino, N., et al., Risk factors and long-term outcome in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab,1996.81(7):p.2647-52.
37.郭兰君,任祖渊,薛辉,常规病理检查未发现垂体腺瘤的Cushing病的临床与病理研究.中华神经外科杂志,1993(9)：p.144-6.
38. Avgerinos, P.C., et al., The corticotropin-releasing hormone test in the postoperative evaluation of patients with cushing's syndrome. J Clin Endocrinol Metab,1987.65(5):p.906-13.
39. Toms, G.C., et al., Predicting relapse after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,1993.76(2):p.291-4.
40. Trainer, P.J., et al., Transsphenoidal resection in Cushing's disease: undetectable serum cortisol as the definition of successful treatment. Clin Endocrinol (Oxf),1993.38(1):p.73-8.
41. Knappe, U.J. and D.K. Ludecke, Persistent and recurrent hypercortisolism after transsphenoidal surgery for Cushing's disease. Acta Neurochir Suppl,1996.65: p.31-4.
42. Arnott, R.D., et al., A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease:prediction of outcome. Acta Endocrinol (Copenh),1990.123(4):p.423-30.
43. Esposito, F., et al., Clinical review:Early morning cortisol levels as a predictor of remission after transsphenoidal surgery for Cushing's disease. J Clin Endocrinol Metab,2006.91(1):p.7-13.
44. Yap, L.B., et al., Undetectable postoperative cortisol does not always predict long-term remission in Cushing's disease:a single centre audit. Clin Endocrinol (Oxf),2002.56(1):p.25-31.
45. Invitti, C., et al., Diagnosis and management of Cushing's syndrome:results of an Italian multicentre study. Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab,1999.84(2):p.440-8.
46. Valero, R., et al., The desmopressin test as a predictive factor of outcome after pituitary surgery for Cushing's disease. Eur J Endocrinol,2004.151(6):p. 727-33.
47. Vignati, F., M.E. Berselli, and P. Loi, Early postoperative evaluation in patients with Cushing's disease:usefulness of ovine corticotropin-releasing hormone test in the prediction of recurrence of disease. Eur J Endocrinol,1994.130(3): p.235-41.
48. Giovanelli, M., M. Losa, and P. Mortini, Surgical therapy of pituitary adenomas. Metabolism,1996.45(8 Suppl 1):p.115-6.
49. Boggan, J.E., J.B. Tyrrell, and C.B. Wilson, Transsphenoidal microsurgical management of Cushing's disease. Report of 100 cases. J Neurosurg,1983. 59(2):p.195-200.
50. Blevins, L.S., Jr., et al., Outcomes of therapy for Cushing's disease due to adrenocorticotropin-secreting pituitary macroadenomas. J Clin Endocrinol Metab,1998.83(1):p.63-7.
51. Vogelstein, B., et al., Clonal analysis using recombinant DNA probes from the X-chromosome. Cancer Res,1987.47(18):p.4806-13.
52. Mashal, R.D., S.C. Lester, and J. Sklar, Clonal analysis by study of X chromosome inactivation in formalin-fixed paraffin-embedded tissue. Cancer Res,1993.53(19):p.4676-9.
53. Thomas, G.A., D. Williams, and E.D. Williams, The demonstration of tissue clonality by X-linked enzyme histochemistry. J Pathol,1988.155(2):p.101-8.
54. Prchal, J.T., et al., Clonal stability of blood cell lineages indicated by X-chromosomal transcriptional polymorphism. J Exp Med,1996.183(2):p. 561-7.
55. Herman, V., et al., Clonal origin of pituitary adenomas. J Clin Endocrinol Metab,1990.71(6):p.1427-33.
56. Dahia, P.L. and A.B. Grossman, The molecular pathogenesis of corticotroph tumors. Endocr Rev,1999.20(2):p.136-55.
57. Solcia E, K.G., Sobin LH., Histological typing of endocrine tumors 2000, Berlin: Springer.1-149.
58. Daita, G., et al., Cavernous sinus invasion by pituitary adenomas--relationship between magnetic resonance imaging findings and histologically verified dural invasion. Neurol Med Chir (Tokyo),1995.35(1):p.17-21.
59. Vallette-Kasic, S., et al., Markers of tumor invasion are major predictive factors for the long-term outcome of corticotroph microadenomas treated by transsphenoidal adenomectomy. Eur J Endocrinol,2000.143(6):p.761-8.
60. Dickstein, G., E. Arad, and C. Shechner, Late complications in remission from Cushing disease. Recurrence of tumor with reinfarction or transformation into a silent adenoma. Arch Intern Med,1997.157(20):p.2377-80.
61. Nagesser, S.K., et al., Long-term results of total adrenalectomy for Cushing's disease. World J Surg,2000.24(1):p.108-13.