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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EOver the past few decades, attempts have been made to develop markers that correlate with the behavior of pituitary adenomas to identify lesions with an increased potential for malignancy (metastasis, invasion, or recurrence following treatment) [Zada G et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E 2011]. This article discusses the role of surgery in the treatment of agressive\/invasive pituitary adenomas.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EPituitary Gland Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENeuroendocrine Tumors\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EWhat Does Surgery Offer for Invasive\/Aggressive Pituitary Adenomas?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-2\u0022\u003EOver the past few decades, attempts have been made to develop markers that correlate with the behavior of pituitary adenomas to identify lesions with an increased potential for malignancy (metastasis, invasion, or recurrence following treatment) [Zada G et al. \u003Cem\u003EJ Neurosurg 2011\u003C\/em\u003E].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EEdward Raymond Laws, MD, Brigham \u0026amp; Women\u0027s Hospital, Boston, Massachusetts, USA, discussed the role of surgery in the treatment of aggressive\/invasive pituitary adenomas.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EPituitary adenomas are common intracranial tumors [Sughrue ME. \u003Cem\u003EPituitary\u003C\/em\u003E 2011]. The overwhelming majority of tumors that arise from the pituitary parenchyma is histologically benign, and as such, death from disseminated central nervous system disease or distant metastasis is exceedingly rare [Chang EF et al. \u003Cem\u003EPituitary\u003C\/em\u003E 2010; Sughrue ME. \u003Cem\u003EPituitary\u003C\/em\u003E 2009].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EStill, pituitary tumors have the ability to dramatically alter a wide range of endocrinological and physiological systems either by secreting supraphysiological levels of pituitary hormones or by interfering with the normal function of the pituitary gland [Sughrue ME. \u003Cem\u003EPituitary\u003C\/em\u003E 2009]. Conceivably, these tumors could alter a patient\u0027s lifespan due to their endocrinological and secondary metabolic effects [Sughre ME. \u003Cem\u003EPituitary\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EMany pituitary adenomas have the capability to invade adjacent parasellar structures; data have demonstrated histological invasion of the dura in up to 80% of macroadenomas and 15% of microadenomas. Invasion of the cavernous sinus dura on either side of the lesion is most common.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EWith the exception of prolactinomas, which are predominantly managed pharmacologically [Marek J. \u003Cem\u003EVnitr Lek\u003C\/em\u003E 2010], transphenoidal microsurgery is the firstline option for treatment for most patients with nonfunctioning pituitary microadenomas or functioning macroadenomas that cause acromegaly or Cushing disease [Castro DG. \u003Cem\u003ERadiation Oncology\u003C\/em\u003E 2010]. However, most aggressive pituitary tumors often require repeated surgery [Colao A. \u003Cem\u003EExpert Opin Pharmacother\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003ESuprasellar extension of a pituitary tumor may lead to invasion of the diaphragm of the sella. Some tumors, particularly in acromegaly, invade inferiorly into the sphenoid sinus. These invasive tumors may present with hormonal hypersecretion and\/or mass effect. The latter includes loss of vision from chiasmal or optic nerve compression and diplopia from paresis of cranial nerves that are responsible for ocular movements. Many dural structures that are involved cannot be removed safely; thus, some invasive tumors are often left behind following surgery and may be responsible for tumor recurrence.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EMost pituitary carcinomas are functioning, with ACTH- and PRL-secreting carcinomas being the most common [Colao A et al. \u003Cem\u003EFront Horm Res\u003C\/em\u003E 2010]. In a recent study of 121 consecutive patients who underwent transphenoidal surgery for pituitary adenomas during an 18-month period, 15% of the tumors met the World Health Organization (WHO) criteria for atypical lesions and tended to be aggressive, invasive macroadenomas; 94% were macroadenomas. On imaging, 83% demonstrated evidence of surrounding invasion compared with 45% of typical adenomas (p=0.004) [Zada G et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EDespite the poor prognosis for aggressive pituitary tumors, surgery can accomplish many goals, including:\u003C\/p\u003E\n         \u003Cul class=\u0022list-unord \u0022 id=\u0022list-1\u0022\u003E\u003Cli id=\u0022list-item-1\u0022\u003E\n               \u003Cp id=\u0022p-11\u0022\u003ERelief of mass effect\u2014restoration of vision, reversal of diplopia\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-2\u0022\u003E\n               \u003Cp id=\u0022p-12\u0022\u003ENormalization of hormonal hypersecretion\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-3\u0022\u003E\n               \u003Cp id=\u0022p-13\u0022\u003ECharacterization of the tumor, including:\u003C\/p\u003E\n               \u003Cul class=\u0022list-unord \u0022 id=\u0022list-2\u0022\u003E\u003Cli id=\u0022list-item-4\u0022\u003E\n                     \u003Cp id=\u0022p-14\u0022\u003EDefinitive pathology\u2014tumor subtype, immunocytochemistry\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-5\u0022\u003E\n                     \u003Cp id=\u0022p-15\u0022\u003EMeasures of proliferation index (Ki-67, MIB-1), mitotic index, classification as typical or atypical\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-6\u0022\u003E\n                     \u003Cp id=\u0022p-16\u0022\u003EOther tumor markers\u2014p53, Pit-1, Galanin\u003C\/p\u003E\n                  \u003C\/li\u003E\u003C\/ul\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-7\u0022\u003E\n               \u003Cp id=\u0022p-17\u0022\u003EAlerts for aggressive behavior\u003C\/p\u003E\n               \u003Cul class=\u0022list-unord \u0022 id=\u0022list-3\u0022\u003E\u003Cli id=\u0022list-item-8\u0022\u003E\n                     \u003Cp id=\u0022p-18\u0022\u003ESilent ACTH adenoma\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-9\u0022\u003E\n                     \u003Cp id=\u0022p-19\u0022\u003EACTH adenoma in Nelson syndrome\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-10\u0022\u003E\n                     \u003Cp id=\u0022p-20\u0022\u003EMammosomatotroph tumors\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-11\u0022\u003E\n                     \u003Cp id=\u0022p-21\u0022\u003EAcidophil stem cell tumors\u003C\/p\u003E\n                  \u003C\/li\u003E\u003Cli id=\u0022list-item-12\u0022\u003E\n                     \u003Cp id=\u0022p-22\u0022\u003EPlurihormonal tumors\u003C\/p\u003E\n                  \u003C\/li\u003E\u003C\/ul\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-13\u0022\u003E\n               \u003Cp id=\u0022p-23\u0022\u003ETissue for molecular studies pertinent to adjunctive medical management; eg, dopamine D2 receptor density\u003C\/p\u003E\n            \u003C\/li\u003E\u003Cli id=\u0022list-item-14\u0022\u003E\n               \u003Cp id=\u0022p-24\u0022\u003EInformation helpful in targeting radiotherapy\/radiosurgery\u003C\/p\u003E\n            \u003C\/li\u003E\u003C\/ul\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EDiagnosis and Nonsurgical Treatment\u003C\/h2\u003E\n         \u003Cp id=\u0022p-25\u0022\u003EGerald Raverot, MD, Hospices Civils de Lyon, Lyon, France, discussed recent advances in the diagnosis and treatment of aggressive pituitary tumors and pituitary carcinomas, classically defined as pituitary tumors with a massive invasion of the surrounding anatomical structures and rapid growth.\u003C\/p\u003E\n         \u003Cp id=\u0022p-26\u0022\u003EWhen aggressive pituitary neuroendocrine tumors develop, conventional treatment options are of limited success. The tumors are notoriously difficult to manage and generally unresponsive to therapy [Colao A. \u003Cem\u003EExpert Opin Pharmacother\u003C\/em\u003E 2011] and thus associated with substantial morbidity and mortality.\u003C\/p\u003E\n         \u003Cp id=\u0022p-27\u0022\u003EApproximately 15% of pituitary tumors are aggressive with a high proliferation rate and a short postoperative time before recurrence. Only metastatic tumors, which account for 0.2% of pituitary tumors, are considered malignant.\u003C\/p\u003E\n         \u003Cp id=\u0022p-28\u0022\u003EEven if, at diagnosis, the presence of metastasis is required to define pituitary carcinomas, lesions are almost invariably first diagnosed as benign pituitary tumors. After a variable period of latency, ranging from a few months to many years, they change their natural course to an aggressive pituitary tumor that is poorly responsive to therapy [Colao A et al. \u003Cem\u003EFront Horm Res\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-29\u0022\u003EPredicting pituitary tumor behavior remains a challenge. In 2004, the WHO developed a new classification for atypical adenomas, based on tumor markers that are thought to correlate with more aggressive pituitary tumor biology. The \u201catypical\u201d variant is defined as: MIB-1 proliferative index greater than 3%, excessive p53 immunoreactivity, and increased mitotic activity [Zada G et al. \u003Cem\u003EJ Neurosurg\u003C\/em\u003E 2011]. The new designation serves as an intermediary between typical pituitary adenomas and pituitary carcinomas.\u003C\/p\u003E\n         \u003Cp id=\u0022p-30\u0022\u003EProf. Raverot and colleagues used a combination of histological and transcriptomic approaches in human prolactin tumors to identify prognostic markers [Wierinckx A et al. \u003Cem\u003EEndocr Relat Cancer\u003C\/em\u003E 2007; Raverot G et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2010] and genomic alterations that are associated with prolactin tumor aggressiveness [Wierinckx A et al. \u003Cem\u003EBrain Pathol\u003C\/em\u003E 2011].\u003C\/p\u003E\n         \u003Cp id=\u0022p-31\u0022\u003ETreatment options are often limited, and although results from chemotherapy have historically been disappointing, it has been reserved as salvage therapy [Kaltsas GA. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2005]. Due to a paucity of reported cases, knowledge of the response to treatment and overall prognosis of patients with aggressive pituitary tumors or carcinomas is sparse [McCormack AI et al. \u003Cem\u003EEur J Clin Invest\u003C\/em\u003E 2011]. However, recent studies reported the successful use of temozolomide, an alkylating agent that is used in the management of glioblastoma and some neuroendocrine tumors, in the management of pituitary carcinomas, with a 60% response rate amongst the published cases [Raverot G et al \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2010].\u003C\/p\u003E\n         \u003Cp id=\u0022p-32\u0022\u003EMoreover, evidence suggests that in pituitary adenomas, both the Raf\/MEK\/ERK and P13K\/Akt\/mTOR pathways are upregulated in their initial cascade, implicating a proproliferative signal disturbance.\u003C\/p\u003E\n         \u003Cp id=\u0022p-33\u0022\u003EAs such, mTOR inhibitors, which have recently been found to have antineoplastic activity in several human cancers, including neuroendocrine tumors, could be a good alternative for temozolomide-resistant pituitary tumors. Similarly, since HER2 overexpression has been demonstrated in prolactin tumors, the HER2\/ErbB2 signaling pathway inhibitor lapatinib could prove useful.\u003C\/p\u003E\n         \u003Cp id=\u0022p-34\u0022\u003EThese recent results, combined with the identification of signaling pathways that are associated with pituitary tumor aggressiveness, open new opportunities for treatment when no other therapeutic options are available.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/5\/22.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzn28q\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}