Neurological Surgery 脳神経外科52巻3号

2024年05月発行

総説

下垂体神経内分泌腫瘍（PitNET）に対する治療の進歩

著者： 西岡宏¹

所属機関： ¹虎の門病院間脳下垂体外科

ページ範囲：P.631 - P.645

Ⅰ はじめに
　下垂体神経内分泌腫瘍（下垂体腫瘍・下垂体腺腫）（pituitary neuroendocrine tumor：PitNET）は，グリオーマなどと比較すると治療に直結する分子生物学的な知見は未だ乏しいが，外科治療・薬物治療ともに近年大きく進歩した．外科治療は大多数が内視鏡下経鼻的に行われており，手術手技や支援器具の進歩などにより成績は飛躍的に向上した．一方，特に機能性腫瘍に対しては有効な薬物治療が複数登場している（Table 1）．さらに，病態の解明や治療効果予測法の進歩などにより，一部の腫瘍では治療にパラダイムシフトが生じている．また，下垂体機能低下症に対するホルモン補充療法に関しても，新たなエビデンス・知見が集積している．長期治療成績の向上に伴い，治療のゴールも外科的治癒・内分泌寛解に加えて，内分泌異常に伴う全身合併症や長期QOLの改善・維持なども含まれるようになり，個別化したprecision medicineが求められるようになった．下垂体腫瘍は「脳腫瘍」としてだけではなく，むしろ「内分泌腫瘍」としての治療，フォローが求められる時代となった．

参考文献

1）Asa SL, et al；attendees of 14th Meeting of the International Pituitary Pathology Club, Annecy, France, November 2016：From pituitary adenoma to pituitary neuroendocrine tumor（PitNET）：an International Pituitary Pathology Club proposal. Endocr Relat Cancer 24：C5-C8, 2017　doi:10.1530/ERC-17-0004

2）Rindi G, Inzani F：Neuroendocrine neoplasm update：toward universal nomenclature. Endocr Relat Cancer 27：R211-R218, 2020　doi:10.1530/ERC-20-0036

3）Asa SL, et al：Overview of the 2022 WHO Classification of Pituitary Tumors. Endocr Pathol 33：6-26, 2022

4）西岡　宏：下垂体腫瘍のWHO組織分類．No Shinkei Geka 51：642-653, 2023

5）Ho K, et al：Pituitary neoplasm nomenclature workshop：does adenoma stand the test of time? J Endocr Soc 5：bvaa205, 2021　doi:10.1210/jendso/bvaa205

6）Hattori Y, et al：Pituitary surgery's epidemiology using a national inpatient database in Japan. Acta Neurochir（Wien）162：1317-1323, 2020

7）Elhadi AM, et al：Evaluation of surgical freedom for microscopic and endoscopic transsphenoidal approaches to the sella. Neurosurgery 11（Suppl 2）：69-78, 2015

8）Nishioka H：Recent evolution of endoscopic endonasal surgery for treatment of pituitary adenomas. Neurol Med Chir（Tokyo）57：151-158, 2017

9）Singh H, et al：Resection of pituitary tumors：endoscopic versus microscopic. J Neurooncol 130：309-317, 2016

10）Fathalla H, et al：Endoscopic versus microscopic approach for surgical treatment of acromegaly. Neurosurg Rev 38：541-549, 2015

11）Starke RM, et al：Endoscopic vs microsurgical transsphenoidal surgery for acromegaly：outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98：3190-3198, 2013

12）Kawamata T, et al：Surgical removal of growth hormone-secreting pituitary adenomas with intensive microsurgical pseudocapsule resection results in complete remission of acromegaly. Neurosurg Rev 28：201-208, 2005

13）Amano K, et al：Repair and prevention of cerebrospinal fluid leakage in transsphenoidal surgery：a sphenoid sinus mucosa technique. Neurosurg Rev 39：123-131, 2016

14）Hadad G, et al：A novel reconstructive technique after endoscopic expanded endonasal approaches：vascular pedicle nasoseptal flap. Laryngoscope 116：1882-1886, 2006

15）Horiguchi K, et al：A new multilayer reconstruction using nasal septal flap combined with fascia graft dural suturing for high-flow cerebrospinal fluid leak after endoscopic endonasal surgery. Neurosurg Rev 39：419-427, 2016

16）Fernandez-Miranda JC, et al：Cavernous sinus compartments from the endoscopic endonasal approach：anatomical considerations and surgical relevance to adenoma surgery. J Neurosurg 129：430-441, 2018

17）Ishida A, et al：Resection of the cavernous sinus medial wall improves remission rate in functioning pituitary tumors：retrospective analysis of 248 consecutive cases. Neurosurgery 91：775-781, 2022

18）Nagata Y, et al：Removal of the medial wall of the cavernous sinus for functional pituitary adenomas：a technical report and pathologic significance. World Neurosurg 126：53-58, 2019

19）Nishioka H, et al：Aggressive transsphenoidal resection of tumors invading the cavernous sinus in patients with acromegaly：predictive factors, strategies, and outcomes. J Neurosurg 121：505-510, 2014

20）Pontes JPM, et al. Efficacy and safety of cavernous sinus medial wall resection in pituitary adenoma surgery：a systematic review and a single-arm meta-analysis. Pituitary 26：340-351, 2023

21）Černý M, et al. Methods of preoperative prediction of pituitary adenoma consistency：a systematic review. Neurosurg Rev 46：11, 2023　doi:10.1007/s10143-022-01909-x

22）de Divitiis E, et al：The current status of endoscopy in transsphenoidal surgery：an international survey. World Neurosurg 83：447-454, 2015

23）Magro E, et al：Complications related to the endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary macroadenomas in 300 consecutive patients. World Neurosurg 89：442-453, 2016

24）Hide T, Fleseriu M：Usefulness of the indocyanine green fluorescence endoscope in endonasal transsphenoidal surgery. J Neurosurg 122：1185-1192, 2015

25）Lim DST, Fleseriu M：Personalized medical treatment of patients with acromegaly：a review. Endocr Pract 28： 321-332, 2022

26）脳ドックのガイドライン2019改訂委員会（編）：脳ドックのガイドライン2019（改訂・第5版）．響文社，札幌，2019

27）間脳下垂体機能障害と先天性腎性尿崩症および関連疾患の診療ガイドライン作成委員会（編）：偶発的下垂体腫瘍（インシデンタローマ）の診断と治療の手引き．間脳下垂体機能障害と先天性腎性尿崩症および関連疾患の診療ガイドライン2023年版．日内分泌会誌99（Suppl）：56-57, 2023

28）Freda PU, et al；Endocrine Society：Pituitary incidentaloma：an endocrine society clinical practice guideline. J Clin Endocrinol Metab 96：894-904, 2011

29）Rajasekaran S, et al：UK guidelines for the management of pituitary apoplexy. Clin Endocrinol（Oxf）74：9-20, 2011

30）Briet C, et al：Pituitary apoplexy. Endocr Rev 36：622-645, 2015

31）Donegan D, Erickson D：Revisiting pituitary apoplexy. J Endocr Soc 6：bvac113, 2022　doi:10.1210/jendso/bvac113

32）Mamelak AN, et al：A prospective, multicenter, observational study of surgical vs nonsurgical management for pituitary apoplexy. J Clin Endocrinol Metab 109：e711-e725, 2024　doi:10.1210/clinem/dgad541

33）Katznelson L, et al；Endocrine Society：Acromegaly：an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99：3933-3951, 2014

34）Fleseriu M, et al：A Pituitary Society update to acromegaly management guidelines. Pituitary 24：1-13, 2021　doi:10.1007/s11102-020-01091-7

35）Gadelha MR, et al：Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol Metab 24：238-246, 2013

36）Zhang S, et al. Correlation between tumor invasion and somatostatin receptor subtypes in acromegaly. J Neurosurg, 2023［published online ahead of print］　doi:10.3171/2023.7.JNS23858

37）Hagiwara A, et al：Comparison of growth hormone-producing and non-growth hormone-producing pituitary adenomas：imaging characteristics and pathologic correlation. Radiology 228：533-538, 2003

38）Wildemberg LE, et al：Machine learning-based prediction model for treatment of acromegaly with first-generation somatostatin receptor ligands. J Clin Endocrinol Metab 106：2047-2056, 2021

39）Giustina A, et al：A consensus on the diagnosis and treatment of acromegaly comorbidities：an update. J Clin Endocrinol Metab 105：e937-e946, 2020　doi.org/10.1210/clinem/dgz096

40）Colao A, et al：Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J Clin Endocrinol Metab 91：85-92, 2006

41）Bolfi F, et al：Mortality in acromegaly decreased in the last decade：a systematic review and meta-analysis. Eur J Endocrinol 179：59-71, 2018

42）Fleseriu M, et al：Prevalence of comorbidities and concomitant medication use in acromegaly：analysis of real-world data from the United States. Pituitary 25：296-307, 2022

43）Gatto F, et al：Current perspectives on the impact of clinical disease and biochemical control on comorbidities and quality of life in acromegaly. Rev Endocr Metab Disord 20：365-381, 2019

44）Fleseriu M, et al：An individualized approach to the management of Cushing disease. Nat Rev Endocrinol 19：581-599, 2023

45）Nishioka H, Yamada S：Cushing's disease. J Clin Med 8：1951, 2019　doi:10.3390/jcm8111951

46）Yamada S, et al：Therapeutic outcomes in patients undergoing surgery after diagnosis of Cushing's disease：a single-center study. Endocr J 62：1115-1125, 2015

47）Nagata Y, et al：Peel-off resection of the pituitary gland for functional pituitary adenomas：pathological significance and impact on pituitary function. Pituitary 22：507-513, 2019

48）Yamada S, et al：Surgical management and outcomes in patients with Cushing disease with negative pituitary magnetic resonance imaging. World Neurosurg 77：525-532, 2012

49）Dickerman RD, Oldfield EH：Basis of persistent and recurrent Cushing disease：an analysis of findings at repeated pituitary surgery. J Neurosurg 97：1343-1349, 2002

50）Pivonello R, et al：Medical treatment of Cushing's disease：an overview of the current and recent clinical trials. Front Endocrinol（Lausanne）11：648, 2020　doi:10.3389/fendo.2020.00648

51）Clayton RN, et al：Mortality in patients with Cushing's disease more than 10 years after remission：a multicentre, multinational, retrospective cohort study. Lancet Diabetes Endocrinol 4：569-576, 2016

52）Yamada S, et al：Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas：a single-center study of 90 cases. J Neurosurg 121：1462-1473, 2014

53）Fukuhara N, et al：Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma. Endocr J 62：21-27, 2015

54）Shimatsu A, et al：Preoperative and long-term efficacy and safety of lanreotide autogel in patients with thyrotropin-secreting pituitary adenoma：a multicenter, single-arm, phase 3 study in Japan. Endocr J 68：791-805, 2021

55）Fukuhara N, et al：Update in pathogenesis, diagnosis, and therapy of prolactinoma. Cancers（Basel）14：3604, 2022　doi:10.3390/cancers14153604

56）Petersenn S, et al. Diagnosis and management of prolactin-secreting pituitary adenomas：a Pituitary Society international Consensus Statement. Nat Rev Endocrinol 19：722-740, 2023

57）Grall-Bronnec M, et al. Dopamine agonists and impulse control disorders：a complex association. Drug Safe 41：19-75, 2018

58）Hu J, et al：Current drug withdrawal strategy in prolactinoma patients treated with cabergoline：a systematic review and meta-analysis. Pituitary 18：745-751, 2015

59）Stiles CE, et al：A meta-analysis of the prevalence of cardiac valvulopathy in patients with hyperprolactinemia treated with cabergoline. J Clin Endocrinol Metab 104：523-538, 2019

60）Zamanipoor Najafabadi AH, et al：Surgery as a viable alternative first-line treatment for prolactinoma patients. A systematic review and meta-analysis. J Clin Endocrinol Metab 105：e32-e41, 2020　doi:10.1210/clinem/dgz144

61）Inoshita N, et al：Immunohistochemical and ultrastructural review of six cases previously diagnosed as null cell PitNETs. Brain Tumor Pathol 40：158-162, 2023

62）Nishioka H, et al：The complementary role of transcription factors in the accurate diagnosis of clinically nonfunctioning pituitary adenomas. Endocr Pathol 26：349-355, 2015

63）Nishioka H, Inoshita N：New WHO classification of pituitary adenomas（4th edition）：assessment of pituitary transcription factors and the prognostic histological factors. Brain Tumor Pathol 35：57-61, 2018

64）Kuo JS, et al：Congress of neurological surgeons systematic review and evidence-based guideline on surgical techniques and technologies for the management of patients with nonfunctioning pituitary adenomas. Neurosurgery 79：E536-E538, 2016　doi:10.1227/NEU.0000000000001390

65）Nishioka H, et al：Inherent tumor characteristics that limit effective and safe resection of giant nonfunctioning pituitary adenomas. World Neurosurg 106：645-652, 2017

66）Zada G, et al：Defining the “edge of the envelope”：patient selection in treating complex sellar-based neoplasms via transsphenoidal versus open craniotomy. J Neurosurg 114：286-300, 2011

67）Nagata Y, et al：Fully endoscopic combined transsphenoidal and supraorbital keyhole approach for parasellar lesions. J Neurosurg 128：685-694, 2018

68）Nishioka H, et al：Simultaneous combined supra-infrasellar approach for giant/large multilobulated pituitary adenomas. World Neurosurg 77：533-539, 2012

69）Dai C, et al：Refractory pituitary adenoma：a novel classification for pituitary tumors. Oncotarget 7：83657-83668, 2016

70）Nishioka H：Aggressive pituitary tumors（PitNET）. Endocrine J 70：241-248, 2023

71）Melmed S, et al：Clinical biology of the pituitary adenoma. Endocr Rev 43：1003-1037, 2022

72）Trouillas J, et al：Are aggressive pituitary tumours and carcinomas two sides of the same coin? Pathologists reply to clinician's questions. Rev Endocr Metab Disord 21：243-251, 2020

73）Saeger W, et al：Two pituitary neuroendocrine tumors（PitNETs）with very high proliferation and TP53 mutation - high-grade PitNET or PitNEC? Endocr Pathol 33：257-262, 2022

74）Raverot G, et al：European Society of Endocrinology. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol 178：G1-G24, 2018　doi:10.1530/EJE-17-0796

75）McCormack A, et al；ESE survey collaborators：Treatment of aggressive pituitary tumours and carcinomas：results of a European Society of Endocrinology（ESE）survey 2016. Eur J Endocrinol 178：265-276, 2018

76）Raverot G, et al：Aggressive pituitary tumours and pituitary carcinomas. Nat Rev Endocrinol 17：671-684, 2021

77）Ilie MD, et al. Therapeutic targeting of the pituitary tumor microenvironment. Pharmacol Ther 250：108506, 2023　doi:10.1016/j.pharmthera.2023.108506

78）Ho KKY, et al：Pituitary adenoma or neuroendocrine tumour：the need for an integrated prognostic classification. Nat Rev Endocrinol 19：671-678, 2023

79）Trouillas J, et al：A new prognostic clinicopathological classification of pituitary adenomas：a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126：123-135, 2013

80）Ho KKY, et al：A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis. Lancet Diabetes Endocrinol 12：209-214, 2024