Clinical significance of pituitary adenoma consistency in patients undergoing endoscopic transsphenoidal surgery

Acitores Cancela, Alberto; Rodríguez Berrocal, Víctor
doi:10.1016/j.endien.2024.09.003
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Pituitary adenomas or pituitary neuroendocrine tumors &#40;PitNETs&#41; are&#44; according to the latest classification&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> one of the most common intracranial neoplasms&#44; with a prevalence in the general population&#44; according to imaging modalities and autopsies&#44; of 10&#37; up to 15&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The vast majority are benign&#44; slow-growing tumors&#46; However&#44; they can have significant clinical repercussions and cause a significantly impaired quality of life&#44; even at very young ages&#44; by causing symptoms due to hormonal excess &#40;acromegaly&#44; Cushing&#8217;s disease&#41; or deficiency &#40;hypopituitarism&#41;&#44; or compressing neighboring structures &#40;loss of vision or oculomotor nerve involvement&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Currently&#44; the first-choice therapy for most of these tumors &#40;except prolactinomas&#41; is surgical excision&#44; primarily through an endonasal endoscopic approach&#44; which achieves very good results&#44; especially in expert hands&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Although most PitNETs &#40;85&#37; up to 90&#37;&#41; are soft tumors&#8212;which greatly facilitates their removal&#8212;there is a 10&#37; up to 15&#37; of hard or fibrous tumors that can significantly complicate the surgical procedure and increase the morbidity and mortality associated with the procedure&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The concept of consistency or hardness in a pituitary tumor is usually subjective and can be difficult to define and standardize&#46; However&#44; in recent years&#44; there has been some consensus on its classification based on well-defined parameters&#46; One of the most detailed categorizations is that of Rutkowski et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> who categorize tumors into 5 different groups&#58; cystic&#44; soft&#44; intermediate&#44; hard&#44; and calcified&#46; However&#44; in our view&#44; and more commonly in the literature&#44; tumors can be categorized into 2 equally discriminative groups &#40;mainly soft vs fibrous&#41;&#46; Soft tumors are those easily aspirated with a conventional 10-Fr aspiration system&#44; while fibrous&#47;hard tumors require pre-fragmentation and dissection with curettes or extracapsular dissection&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It is still to be elucidated which factor or factors determine an increased consistency in these tumors&#46; Primarily&#44; an increase in collagen fibers &#40;types I&#44; III&#44; and IV&#41; has been associated&#44; as well as a higher expression of transforming growth factor beta-1 &#40;TGF-&#946;1&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a> Certain histological subtypes have been associated with softer &#40;corticotropinomas&#41; or fibrous&#47;hard &#40;thyrotropinomas&#41; consistencies&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Previous medical therapies &#40;dopaminergic agonists&#44; somatostatin analogs&#44; or even temozolomide&#41; have been associated with changes in tumor consistency with controversial results&#46; Some studies have linked the preoperative administration of bromocriptine in the management of prolactinomas with more fibrosis of the adenoma&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Regardless of the cause&#44; this increased consistency in some tumors seems to influence their clinical presentation&#46; Hard tumors have been more frequently associated with hormonal deficiency&#44; larger size&#44; and visual deficit&#44; although this can be difficult to separate from other tumor characteristics&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Regarding surgical treatment&#44; it also seems evident that a more fibrous consistency of the adenoma could influence both the outcomes and prognosis&#46; The surgical technique varies in these cases&#44; often requiring tumor fragmentation and extraglandular dissection&#44; thus leading to greater manipulation of the normal gland&#46; Recent reports have shown that more fibrous consistency is associated with lower rates of complete resection vs soft tumors &#40;48&#46;7&#37; vs 76&#46;3&#37;&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;8</span></a> implying that patients usually receive adjuvant therapies after surgery up to 3 times more frequently&#46; Moreover&#44; these fibrous tumors are associated with a higher probability of surgical complications&#44; such as the intraoperative rupture of the sellar diaphragm with cerebrospinal fluid &#40;CSF&#41; leakage&#44; which is 5 times more common in fibrous tumors&#8212;requiring more complex reconstructive techniques during closure&#8212;or postoperative panhypopituitarism and permanent diabetes insipidus&#44; both being up to 10 times more common in surgical procedures of fibrous tumors&#46; This is due to the above-mentioned glandular and tumor manipulation&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> While it is true that analyzing these results in isolation is complex due to factors such as tumor size&#44; cavernous sinus invasion&#44; or age&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> these findings persist after performing multivariable statistical analyses to control for these confounding factors&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It seems logical that&#44; in this context&#44; if the subgroup of patients with hard or fibrous tumors could be preoperatively identified&#44; they could theoretically be referred to highly experienced surgeons in the management of this disease within multidisciplinary reference units&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Therefore&#44; in the last 10 to 15 years&#44; efforts have been made to predict the consistency of these pituitary tumors based on preoperative radiological imaging modalities&#8212;mainly brain MRI&#8212;which have experienced significant advancements in recent years&#46; The goal is to inform patients more precisely and individually about their tumor expectations and management and plan surgery more accurately&#46; However&#44; attempts to predict tumor consistency have been unsuccessful&#44; often yielding contradictory results&#46; Analyses of diffusion sequences&#44; perfusion&#44; T1 contrast uptake&#44; T2 behavior&#44; and even more complex analyses&#8212;elastography&#8212;have shown multiple inconsistent results&#46; Therefore&#44; we believe that&#44; probably&#44; and&#44; at least&#44; for now&#44; using radiology as a standalone method to predict tumor consistency will not fully resolve the issue&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> Recently&#44; we have proposed a predictive model that considers not only preoperative radiological characteristics but also other clinical and biochemical criteria that have proven effective in predicting tumor consistency&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Additionally&#44; to simplify its application&#44; we have designed and published a scale to facilitate its use&#8212;the pituitary tumor consistency &#91;PiTCon&#93; score&#8212; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is obvious that although this is just a first step that needs to be validated through multicentric studies with a larger number of patients&#44; we believe it may be a step in the right direction&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Consistency&#44; cavernous sinus invasion&#44; tumor size&#44; and previous treatments&#8212;whether surgery or radiotherapy&#8212;are&#44; therefore&#44; variables that determine the difficulty of surgical removal&#44; affecting outcomes and marking patient progression&#46; Except for the first-mentioned variable&#44; the rest are easily identifiable in our office via radiology and the patient&#39;s health record&#46; Therefore&#44; we believe it is important to try to predict PitNET consistency as well&#44; thus completing a sort of screening of complex patient cases&#44; which could be individually referred to specialized units and reference centers &#40;SURF&#41; to maximize the chances of cure and minimize complications&#44; thereby improving these patients&#8217; quality of life&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0050" class="elsevierStylePara elsevierViewall">None declared&#46;</p></span></span>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Panhypopituitarism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Craniocaudal extent &#40;mm&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60; 20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#8805; 20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Previous surgery</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
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                      "titulo" => "Recomendaciones sobre el diagn&#243;stico y seguimiento radiol&#243;gico de los tumores neuroendocrinos hipofisarios"
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                          "etal" => true
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                            0 => "NA Tritos"
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                    0 => array:2 [
                      "doi" => "10.1001/jama.2023.5444"
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                        "tituloSerie" => "JAMA"
                        "fecha" => "2023"
                        "volumen" => "329"
                        "numero" => "16"
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                      "titulo" => "Reported outcomes in transsphenoidal surgery for pituitary adenomas&#58; a systematic review"
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                          "etal" => true
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                            3 => "R&#46;T&#46;S&#46; Loh"
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                        "numero" => "2"
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                      "titulo" => "Effect of pituitary adenoma consistency on surgical outcomes in patients undergoing endonasal endoscopic transsphenoidal surgery"
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                      "titulo" => "Is it possible to predict the development of diabetes insipidus after pituitary surgery&#63; Study of 241 endoscopic transsphenoidal pituitary surgeries"
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                      "titulo" => "Development and clinical validation of a grading system for pituitary adenoma consistency"
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                          "etal" => true
                          "autores" => array:6 [
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                        "tituloSerie" => "J Neurosurg"
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                      "titulo" => "Clinical relevance of tumor consistency in pituitary adenoma"
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                          "autores" => array:6 [
                            0 => "A&#46; Acitores Cancela"
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                            2 => "H&#46; Pian"
                            3 => "JS Mart&#237;nez San Mill&#225;n"
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