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Surgical and postsurgical management of abdominal paragangliomas and pheochromocytomas
Manejo quirúrgico y posquirúrgico de paragangliomas abdominales y feocromocitomas
M. Araujo-Castroa,
Corresponding author
marta.araujo@salud.madrid.org

Corresponding author.
, E. Pascual-Corralesa, J. Lorca Álvarob, C. Mínguez Ojedab, H. Pianc, I. Ruz-Caracuelc, A. Sanjuanbenito Dehesad, A.B. Serrano Romeroe, T. Alonso-Gordoaf, J. Molina-Cerrillof, V. Gómez Dos Santosb
a Departamento de Endocrinología y Nutrición, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain
b Departamento de Urología, Hospital Universitario Ramón y Cajal, Madrid, Spain
c Departamento de Anatomía Patológica, Hospital Universitario Ramón y Cajal, Madrid, Spain
d Departamento de General y Cirugía Digestiva, Hospital Universitario Ramón y Cajal, Madrid, Spain
e Departamento de Anestesia, Hospital Universitario Ramón y Cajal, Madrid, Spain
f Departamento Médico Oncológico, Hospital Universitario Ramón y Cajal, Madrid, Spain
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Surgical treatment algorithm in pheochromocytomas&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#42; Consider the retroperitoneal approach in case of previous abdominal surgery&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42; In selected cases&#44; one-stage surgery with repositioning of the patient may be considered&#46; Same approach considerations depending on the size of the lesion&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42;&#42; Excision or ablative treatment of resectable metastases will be considered if the general situation of the patient &#40;ECOG or PS&#41; allows it&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Regarding adrenal &#8220;conservative&#8221; surgery&#44; it has not been introduced in the hospital&#44; but we believe that at this time it could be considered in the case of bilateral lesions or contralateral recurrence after previous adrenalectomy&#44; and after its discussion in the endocrine tumour board&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pheochromocytomas and paragangliomas &#40;PGLs&#41; are rare neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or neural crest progenitors located outside of the adrenal gland&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> PGLs can be located throughout the entire organism and are classified as sympathetic and parasympathetic depending on their origin&#46; Pheochromocytomas and most PGLs of the thorax&#44; abdomen&#44; and pelvis are sympathetic&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Currently&#44; there is consensus that &#945;-adrenergic blockade should be initiated preoperatively<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> to reduce the risk of perioperative and intraoperative complications in catecholamine secreting tumours&#46; Furthermore&#44; the only curative treatment option of pheochromocytomas&#47;PGLs is surgical resection&#46; Surgery is a corner stone in control of hypersecretion and tumour growth&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The choice of surgical approach is determined based on several factors such as the location of the lesion&#44; size&#44; patient&#180;s body habitus and the likelihood of malignancy&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The basic principles in surgery for pheochromocytoma and abdominal PGL include early identification and ligation of the adrenal vein&#44; minimal manipulation of the tumour to prevent tumour rupture or the release of catecholamines&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Surgery of pheochromocytoma and abdominal PGL performed by advanced laparoscopic surgeons and high-volume adrenal surgeons &#40;4&#8211;6 adrenalectomies&#47;year&#41; have shown to improve surgical results&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this article&#44; we detail our current protocol for the surgical and postsurgical management of abdominal PGLs and pheochromocytomas&#44; with a special focus on the need of a multidisciplinary team for the management of these cases&#44; and in centres with experience in this pathology&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">The physicians involved in the management of patients with abdominal PGLs and pheochromocytomas of our hospital reviewed systematically current knowledge on the surgical management of abdominal PGLs and pheochromocytomas&#46; The literature review used the online Entrez-PubMed facilities&#44; including only publications in English and Spanish published from 2010 to 2021&#46; After careful selection&#44; more than 200 papers were reviewed&#44; of which only 40 were used to elaborate the current protocol&#46; The adrenal multidisciplinary team elaborated a first draft that was presented and perfected in a formal presentation with other doctors involved in the management of adrenal tumours&#46; The protocol was subsequently approved by the Hospital Quality Unit&#46; Our hospital meets criteria to be considered a referral centre having an experienced urologists and general surgeons with more than 150 adrenalectomies performed in the last 5 years&#44; an average of 25&#8211;30 surgeries per year&#46; The rate of intraoperative complications in the pheochromocytoma surgery is of 14&#37; and of postoperative complications of 20&#37;&#46; The mortality rate in the last 5 years was of 0&#37;&#46; The median hospital stay was 5 days &#40;range 3&#8211;13&#41;&#46; Furthermore&#44; this center participate in the multicentric national PHEO-RISK study that has included 162 adrenalectomies performed in 159 patients with pheochromocytomas&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Moreover&#44; a previous study shows the current protocol for presurgical management and anesthetic management of pheochromocytomas and sympathetic PGLs&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Surgical management of abdominal PGLs and pheochromocytomas</span><p id="par0025" class="elsevierStylePara elsevierViewall">Abdominal PGLs and pheochromocytomas represent the 80&#37;&#8211;85&#37; of all neuroendocrine chromaffin cells tumours&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Nearly 5&#37; of patients with adrenal incidentalomas prove to have a pheochromocytoma and approximately 40&#37; of these patients have germline mutations&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The decision on the type of surgical approach depends mainly on the aetiology of the lesion&#44; size&#44; likelihood of malignancy and patient&#180;s body habitus&#46; The optimal approach is also based on the experience and preference of the surgeon&#46; At present&#44; laparoscopic surgery is considered the gold standard approach for pheochromocytomas&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; the level of competence for the open approach must be maintained in case of both the need for reconversion and the primary indication&#46; <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a> indicate the surgical treatment algorithm of our Urology and General Surgery services for pheochromocytomas and abdominal PGLs&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> describes the main approaches for abdominal PGL and pheochromocytoma surgery&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laparoscopic adrenalectomy</span><p id="par0035" class="elsevierStylePara elsevierViewall">In hands of experienced surgeons&#44; laparoscopy can be performed safely while preserving the principles of oncological surgery&#44; with similar results to open surgery&#46; The basic principles during surgery are to prevent direct manipulation or application of pressure to the tumour in order to avoid rupture of the tumour capsule&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Laparoscopic adrenalectomy has even been proposed in selected cases of potentially malignant or locally aggressive pheochromocytomas and PGLs in experienced centres&#44; with oncological results that are equivalent to the open approach&#44; while providing advantages in terms of patient morbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Laparoscopy offers better visualization of the adrenal gland and faster access to the adrenal vein&#44; further reducing the risk of catecholamine release&#46; However&#44; some studies have suggested that intra-abdominal insufflation during laparoscopy alone may cause an increase in serum catecholamines&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> This fact can be minimized by slow and progressive inflation and the use of low intra-abdominal pressures&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Tumour size has been a basic consideration in laparoscopic adrenalectomy&#46; In this way&#44; the Endocrine Surgery Society guidelines suggest open surgery in tumours greater than 6&#8239;cm due to initial doubts regarding the possibility of obtaining safe oncological margins and the increased perceived risk of capsular rupture&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;12</span></a> However&#44; some observational&#44; controlled studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;14</span></a> that have compared both open and laparoscopic approaches did not show differences in the rate of recurrence and equivalent perioperative outcomes between both approaches&#46; Therefore&#44; laparoscopic resection of large pheochromocytomas requires previous experience&#44; and potentially malignant tumours should not be considered as an absolute contraindication for laparoscopic excision&#44; as long as oncological principles should be strictly followed avoiding capsular rupture&#46; There is agreement that potentially malignant tumours larger than 10&#8239;cm or those with possible infiltration of adjacent organs should be approached by open surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Transperitoneal and retroperitoneal laparoscopic surgery</span><p id="par0045" class="elsevierStylePara elsevierViewall">The lateral transperitoneal laparoscopic approach is currently the most widely used for unilateral adrenalectomy due to the familiarity of the intra-abdominal anatomy and the large working space&#46; However&#44; the retroperitoneal approach provides direct access to the adrenal tumour&#44; avoiding possible injury to the intra-abdominal organs&#46; Both approaches have shown similar efficacy and safety for small tumours&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The transperitoneal laparoscopic approach has been widely used for adrenal tumours of all sizes due to excellent anatomical exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The patient is placed in the lateral decubitus position&#44; and the table is flexed to maximize the space between the costal margin and the iliac crest&#46; Full lateral decubitus makes repositioning for bilateral tumours difficult&#46; The workspace in retroperitoneal approach is more limited than in the transperitoneal approach&#46; It requires important surgeon experience being potentially more difficult for larger masses or obese patients with increased retroperitoneal fat&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The patient location is more lateral position than transperitoneal approach&#46; The surgical table is slightly flexed to open the space between the costal margin and the iliac crest&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The most frequent causes of conversion to open surgery are the difficulty in controlling bleeding or the need to secure the oncological margins&#46; The incidence of deep vein thrombosis in laparoscopic adrenalectomy can reach up to 4&#37; of patients&#44; therefore antithrombotic prophylaxis should be considered according to clinical thromboprophylaxis guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Robotic adrenalectomy</span><p id="par0060" class="elsevierStylePara elsevierViewall">Robotic adrenalectomy has similar results to laparoscopic adrenalectomy&#46; Some authors argue that robotic surgery is useful for larger tumours and bilateral and partial adrenalectomies as it provides additional degrees of freedom of movement for the surgeon&#46; However&#44; the costs associated with the robotic surgery are greater than conventional laparoscopy&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> A recent randomized controlled trial comparing robotic versus laparoscopic adrenalectomy for pheochromocytoma<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> described some advantages of robotic adrenalectomy&#44; including shorter median operative time &#40;92&#46;5 vs 122&#46;5&#8239;min&#44; P&#8239;&#61;&#8239;0&#46;007&#41; and significant lower blood loss and operative time compared with the conventional laparoscopic group &#40;P&#8239;&#60;&#8239;0&#46;05&#41;&#46; A recent metaanalysis concluded that he robotic adrenalectomy for pheochromocytoma achieve better outcomes over laparoscopic approach in terms of safety and efficacy&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Single-Site Laparoscopy &#40;LESS&#46; Laparoendoscopic Single-Site&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">LESS is a laparoscopic technique that uses a single skin incision&#46; It offers a better cosmetic result and a short convalescence&#44; but it turns out to be more technically demanding due to the loss of triangulation of the instruments&#46; Nevertheless&#44; a systematic review and meta-analysis of LESS versus conventional adrenalectomy<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> could not show a difference in estimated blood loss or length of hospital stay&#44; but surprisingly neither in cosmetic results&#44; recovery time&#44; or laparoscopic port-related complications&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Open surgery</span><p id="par0070" class="elsevierStylePara elsevierViewall">Open surgery or laparotomy is chosen when faced with a high risk of metastatic disease &#40;eg&#44; SDHB mutations&#41; or for multifocal lesions where a laparoscopic approach may not be feasible&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a> Nevertheless&#44; although the patient has a SDHB mutation&#44; if there is no evidence of metastatic disease or infiltrative disease in the CT or MR&#44; laparoscopic resection may be chosen &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Although the reoperation is not a contraindication due to the minimally invasive approach&#44; it may be a better indication for open surgery&#46; Although&#44; there is no precise threshold for the tumour diameter to indicate open approach&#44; it is generally recommended for tumours over 6&#8239;cm without malignancy or malignancy with no local invasion&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;23</span></a> Open resection is also usually recommended for abdominal paragangliomas as they are more likely to be malignant and are frequently found in areas difficult for laparoscopic resection&#44; but laparoscopic resection can be performed for small&#44; non-invasive paragangliomas in surgically favourable locations&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Open surgery is usually performed using a transperitoneal anterior approach&#46; The lateral extraperitoneal approach is a good choice for obese patients&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Cortical preservation surgery or partial adrenalectomy</span><p id="par0075" class="elsevierStylePara elsevierViewall">Partial adrenalectomy would be acceptable in cases of benign lesions with high rates of multifocality and bilaterality and recurrence are expected&#44; such as in VHL and MEN 2 syndromes&#46; A recent study even has suggested to consider partial adrenalectomy in all patients with hereditary pheochromocytoma&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> The VHL and MEN 2 syndromes have a high probability &#40;40&#8211;50&#37; in VHL&#59; &#62;50&#37; in MEN 2&#41; of developing bilateral pheochromocytomas&#44; either synchronously or metachronous&#44; while the probability of metastasis is very low&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> In bilateral pheochromocytomas&#44; removal of the tumour alone versus the entire adrenal gland remains controversial&#46; Cortical sparing surgery was introduced into practice in 1999&#44; although it remains a relatively underused procedure&#46; A recent meta-analysis<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> concluded that cortical preservation during adrenalectomy may reduce the need for steroid replacement therapy &#40;23&#37; of patients with cortical preservation developed adrenal insufficiency&#41; and carries a low risk of recurrence &#40;in 8&#8211;10&#37; of patients&#44; mostly in patients with VHL and MEN 2&#41;&#44; based mainly on retrospective studies and limited sample size&#46; The surgical goal is to leave enough adrenal cortex&#44; about 30&#37;&#44; with an adrenal vein preserved in situ to prevent adrenal insufficiency and consequently steroid replacement therapy for life&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Cortical sparing adrenalectomy can be performed openly or minimally invasive&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> Although there is a wide variation regarding the technical aspects of this complex procedure&#44; there is agreement on some points&#46; Before mobilization and devascularization of the gland&#44; intraoperative ultrasound is recommended to define the anatomy of the pheochromocytoma in relation to normal adrenal gland and adrenal vein&#46; This will optimize surgical planning and allow the surgeon to de-vascularize only the portion of the adrenal to being resected&#46; Additionally&#44; ultrasound will help exclude additional ipsilateral pheochromocytomas&#46; Both transperitoneal and retroperitoneal approaches have been described&#44; being safe and feasible techniques&#46; The same can be said regarding robotic partial adrenalectomy whose results are pretty similar to conventional laparoscopy&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Surgery of metastatic pheochromocytomas and PGLs</span><p id="par0085" class="elsevierStylePara elsevierViewall">It is estimated that approximately 10&#37; of pheochromocytomas and 25&#37; of PGLs are metastatic&#46; Nevertheless&#44; rates of malignancy vary depending on the genetic context and the anatomical site of origin &#40;for example&#44; 2&#8211;4&#37; jugulotympanic&#44; 4&#8722;6&#37; carotid body or 10&#8211;19&#37; vagal tumours&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;28</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">All cases should be discussed in a multidisciplinary reference team specializing in complex cases of pheochromocytoma&#47;PGL with the aim of optimize the treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> All patients with a hormonally functional secreting pheochromocytoma&#47;PGL should undergo preprocedural blockade for 7&#8211;14 days before procedure&#44; including for surgery and for most localized and systemic therapies to prevent periprocedural cardiovascular complications&#46; Regarding surgery&#44; when complete resection is possible&#44; it may be beneficial&#59; however&#44; when resection will leave residual metastatic disease&#44; the benefits may be less clear&#46; Nevertheless&#44; surgical debulking should be considered in patients with metastatic disease with good overall health and without evidence of massive multiple metastases&#46; Resection of the primary lesion in metastatic disease has some potential benefits&#58; i&#41; in those patients with functional tumours&#44; an improvement in symptoms related to catecholamine excess is expected with the reduction in tumour burden and ii&#41; it has been shown to improve overall survival&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> If curative surgical resection cannot be performed&#44; debulking surgery can still be considered&#44; as it may improve the efficacy of other treatment options such as targeted radiation therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> Postoperative biochemical response is more common in patients with disease confined to the abdomen than those with extra-abdominal disease&#46; If we accept that there is a benefit to resection of the primary PGL&#47;pheochromocytoma&#44; the open approach is of choice&#44; although laparoscopic resection should be performed when complete resection with an intact capsule can be achieved&#46; Surgery includes locoregional lymphadenectomy at the time of laparotomy&#44; in addition to resection of the primary tumour&#46; As a general recommendation&#44; lymph node dissection should be considered for larger or locally invasive tumours&#44; or when preoperative imaging or intraoperative exploration suggest node involvement&#46;</p></span></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Postsurgical management</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Post-surgical anesthetic treatment</span><p id="par0095" class="elsevierStylePara elsevierViewall">Although immediate postoperative care in an intensive care unit is not necessary in most patients&#44; admission to a postanaesthetic recovery unit is advisable during the first 24&#8239;h after surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> Some risk factors of postoperative complications after resection of a pheochromocytoma have been described&#44; such as body mass index&#44; ischemic heart disease&#44; tumour size&#44; intraoperative hemodynamic instability and the use of crystalloid-colloids in the preoperative period&#46; The most frequent postoperative complications are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">a&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Hyperglycaemia-hypoglycaemia&#58;</span></span> Pheochromocytoma patients are usually hyperglycemic due to suppression of insulin release from pancreatic &#946; cells and increased glycogenolysis&#46; The treatment is carried out with insulin according to the blood glucose levels&#46; Tumour resection results in hyperinsulinemia with subsequent hypoglycaemia&#44; which may appear in up to 15&#37;&#8211;20&#37; of operated patients&#46; In this case&#44; the treatment will be carried out with the contribution of glucose&#46; It is advisable to monitor blood glucose levels every 4&#8722;6&#8239;h in the first postoperative days&#46; So&#44; plasma glucose levels should be monitored closely for the first 48&#8239;h after surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">b&#41;</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Prolonged drowsiness&#58;</span></span> It usually occurs in the first 48&#8239;h after surgery&#46; It is favoured by prolonged &#940; adrenergic blockade&#46; It is necessary to be cautious with the added administration of drugs that promote respiratory depression&#44; especially opiates&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">c&#41;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Hypertension&#58;</span></span> 30&#37; of patients remain hypertensive after tumour resection due to the storage of high levels of catecholamines in the nerve endings&#46; Sometimes the cause of hypertension is also hypervolemia in relation to excessive fluids been administered&#44; or the recovery of autonomic reflexes&#44; inadvertent ligation of the renal artery or the persistence of the tumour&#46; Hypertension usually returns to normal a week after surgery&#46; The drugs of choice are esmolol or &#940;-blockers&#46; Paroxysmal arterial hypertension occurs in 27&#8211;38&#37;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> of patients operated on for pheochromocytoma and is more frequent in cases of familial hypertension and in older patients&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">d&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Persistent arterial hypotension</span></span><a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a><span class="elsevierStyleBold">&#58;</span> It is usually due to blood loss&#44; impaired vascular compliance&#44; or residual effects of preoperative adrenergic blockade&#46; The treatment will be carried out depending on which we think is the cause that originates it&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">e&#41;</span><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold"><span class="elsevierStyleItalic">Heart failure and acute lung edema</span></span>&#58; they are due to both the excess volume administered and an effect and &#946; adrenergic effect&#46;</p></li></ul></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Evaluation of pathological anatomy results</span><p id="par0125" class="elsevierStylePara elsevierViewall">The specimen should be sent to the Surgical Pathology department in the shortest possible time after surgical removal&#44; to minimize cold ischemia time&#46; Shipping fresh allows freezing samples to be taken&#44; before fixation&#44; for the Biobank or for genetic studies in the cases deemed convenient&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The piece should be measured and weighed &#40;in cases with abundant surrounding adipose tissue&#44; the tumour will be reweighed once this adipose tissue has been removed&#41;&#46; The specimen must be oriented&#44; and the surface marked with ink to correctly identify the surgical margin&#46; Subsequently&#44; cross sections will be made&#46; Fixation in formalin should be carried out for 24&#8239;h&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">During the grossing&#44; special attention should be paid to foci of necrosis and haemorrhage that can be macroscopically identified&#46; In addition&#44; abundant tissue from the surrounding tumour-parenchyma interface should be included to histologically assess the parameters of capsular invasion&#44; infiltration of adipose tissue&#44; and vascular invasion&#46; All macroscopically differentiable areas should be included&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In the microscopic evaluation of the tumour&#44; the histological parameters necessary to perform include the PASS<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> prognostic scales in pheochromocytoma and GAPP<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> in pheochromocytoma and PGL<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#41;&#46; Currently&#44; the existence of malignant pheochromocytomas and PGLs is not readily recognized on the pathology specimen but a risk of metastasis is assigned to each tumour&#44; unless the patient already has metastatic deposits in nonchromaffin tissue sites such as bone&#44; liver or lymph nodes&#46; Based on a recent meta-analysis with 809 pheochromocytomas&#44; a score greater than 4 has a low positive predictive value of metastasis &#40;31&#37;&#41; but a score less than 4 has a high negative predictive value of metastasis &#40;99&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The GAPP scale requires knowing the metabolites produced by the tumour and the final score is transformed into a grade on a scale of three&#46; The higher the grade&#44; the greater the risk of metastasis&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0145" class="elsevierStylePara elsevierViewall">Additionally&#44; immunohistochemistry for SDH-B is performed for two purposes&#46; The first purpose is to screen for mutations in the SDH-B&#44; SDH-C and SDH-D genes&#46; Immunohistochemical loss of SDH-B has been associated with mutations in these genes&#44; showing in the original series a sensitivity of 100&#37; &#40;95&#37; CI 87&#8211;100&#41; and a specificity of 84&#37; &#40;95&#37; CI 60&#8211;97&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> The second aim is to use it as a predictor of metastasis&#44; since patients with mutations in the SDH genes have a higher risk of metastasis and of presenting multicentric pheochromocytomas &#47; PGLs&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> In fact&#44; there is a modified GAPP scale that includes the result of immunohistochemistry for SDH-B&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Postoperative hormonal evaluation</span><p id="par0150" class="elsevierStylePara elsevierViewall">Metanephrine levels in plasma or urine should be measured between 2 and 6 weeks after surgery in patients who had elevated levels before the intervention&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a> In patients operated of metanephrine-producing tumours&#44; the presence of elevated postoperative metanephrine levels strongly suggests persistent disease&#46; In these cases&#44; imaging tests are needed to confirm the presence of residual catecholamine secreting tissue and locate it&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In those patients with normal preoperative levels of metanephrines and high preoperative levels of chromogranin A&#44; it is advisable to analyse plasma levels of chromogranin A 2&#8211;6 weeks after surgery since in these cases they can serve as an alternative biochemical marker&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">It is advisable during follow-up to perform annual biochemical tests for lifetime with measurement of metanephrines in plasma or urine to detect local or metastatic recurrence or new tumours&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Postoperative radiological evaluation or other tests</span><p id="par0165" class="elsevierStylePara elsevierViewall">An imaging test is recommended 3 months after surgery in the following cases<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>&#58; i&#41; patients operated for pheochromocytoma and PGL who have elevated levels of metanephrines in the postoperative period&#59; ii&#41; patients in whom metanephrine levels were normal before surgery and iii&#41; patients in whom metanephrine levels were not measured before surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The best imaging technique or optimal time interval for periodic follow-up images is unknown&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Imaging tests are recommended every 1&#8211;2 years in patients undergoing surgery for pheochromocytoma or biochemically inactive PGL to detect local or metastatic recurrences or new tumours&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In addition&#44; imaging tests are the only follow-up option in those cases in which there are no reliable biochemical markers that are mainly useful in patients with head and neck PGLs&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">In the case of hereditary pheochromocytomas and PGLs&#44; a personalized follow-up is advised&#44; taking into account the different genotype-phenotype presentations&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In patients with SDHx mutations&#44; thoracoabdominopelvic CT and head and neck magnetic resonance angiography &#40;MRI&#41; should be performed&#46; However&#44; to avoid ionizing radiation&#44; it is also advisable to perform MRI to detect biochemically silent tumours and reserve imaging modalities by CT and nuclear medicine to better characterize the tumours detected&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;7</span></a></p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0180" class="elsevierStylePara elsevierViewall">Surgery represents the treatment of choice of most abdominal PGLs and pheochromocytomas&#46; For the proper selection of the surgical approach&#44; the location and size of the tumour and the patient&#180;s body habit and the likelihood of malignancy should be considered&#46; Moreover&#44; a proper presurgical evaluation and treatment with alpha- and beta-adrenergic blockade should be performed to reduce the risk of perioperative and intraoperative complications&#46; Optimal postsurgical evaluation&#44; including hemodynamic&#44; pathological&#44; hormonal&#44; and radiological evaluation&#44; should be performed by a multidisciplinary team specializing in PGL&#47;pheochromocytoma management&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Surgical management of abdominal PGLs and pheochromocytomas"
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                  "titulo" => "Laparoscopic adrenalectomy"
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                      "titulo" => "Transperitoneal and retroperitoneal laparoscopic surgery"
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                      "titulo" => "Robotic adrenalectomy"
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                      "titulo" => "Single-Site Laparoscopy &#40;LESS&#46; Laparoendoscopic Single-Site&#41;"
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                  "titulo" => "Open surgery"
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                  "titulo" => "Cortical preservation surgery or partial adrenalectomy"
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                  "titulo" => "Surgery of metastatic pheochromocytomas and PGLs"
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          "titulo" => "Postsurgical management"
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              "titulo" => "Evaluation of pathological anatomy results"
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              "titulo" => "Postoperative hormonal evaluation"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2022-05-19"
    "fechaAceptado" => "2022-05-30"
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        0 => array:4 [
          "clase" => "keyword"
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          "identificador" => "xpalclavsec1713360"
          "palabras" => array:4 [
            0 => "Pheochromocytomas"
            1 => "Abdominal paragangliomas"
            2 => "Laparoscopic surgery"
            3 => "Partial adrenalectomy"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec1713362"
          "palabras" => array:2 [
            0 => "PGL"
            1 => "SDHB"
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          "palabras" => array:4 [
            0 => "Feocromocitomas"
            1 => "Paragangliomas abdominales"
            2 => "Cirug&#237;a laparosc&#243;pica"
            3 => "Suprarrenalectom&#237;a parcial"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Purpose</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">To describe our current protocol for surgical and postsurgical management of abdominal paragangliomas &#40;PGLs&#41; and pheochromocytomas&#44; with a special focus on multidisciplinary management in centres with experience&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The physicians involved in the management of patients with abdominal PGLs and pheochromocytomas of our hospital reviewed systematically current knowledge on the surgical management of abdominal PGLs and pheochromocytomas&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Currently&#44; surgery is considered the treatment of choice for abdominal PGLs and pheochromocytomas&#46; The choice of surgical approach is determined based on the location of the lesion&#44; size&#44; patient&#769;s body habitus and the likelihood of malignancy&#46; Laparoscopic surgery is usually considered the gold standard approach for pheochromocytomas&#44; but open access should be considered in invasive and&#47;or potentially malignant tumours &#62;8&#8211;10&#8239;cm and for abdominal PGLs&#46; Postsurgical management of pheochromocytomas and PGLs includes close hemodynamic monitoring and treatment of postsurgical complications&#44; the pathological study of the surgical specimen&#44; reassessment of hormonal and&#47;or radiological status and planning of follow-up based on the risk of recurrence and malignancy&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Surgery represents the treatment of choice of most abdominal PGLs and pheochromocytomas&#46; Optimal postsurgical evaluation&#44; including hemodynamic&#44; pathological&#44; hormonal&#44; and radiological evaluation&#44; should be performed by a multidisciplinary team specializing in PGL&#47;pheochromocytoma management&#46;</p></span>"
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          1 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Describir nuestro protocolo actual para el manejo quir&#250;rgico y posquir&#250;rgico de los paragangliomas abdominales &#40;PGL&#41; y los feocromocitomas&#44; con especial atenci&#243;n en el manejo multidisciplinar en centros con experiencia&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Los facultativos implicados en el tratamiento de pacientes con PGL abdominales y feocromocitomas de nuestro hospital revisaron sistem&#225;ticamente la bibliograf&#237;a actual sobre el tratamiento quir&#250;rgico de los PGL abdominales y feocromocitomas&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">La cirug&#237;a se considera el tratamiento de primera elecci&#243;n para los PGL abdominales y feocromocitomas&#46; La decisi&#243;n sobre el abordaje quir&#250;rgico se basa en la localizaci&#243;n y el tama&#241;o de la lesi&#243;n&#44; la constituci&#243;n corporal del paciente y la probabilidad estimada de malignidad&#46; La cirug&#237;a laparosc&#243;pica suele considerarse el m&#233;todo de referencia para los feocromocitomas&#44; pero el abordaje abierto debe considerarse en los tumores invasivos y&#47;o potencialmente malignos de m&#225;s de 8&#8211;10&#8239;cm y en los PGL abdominales&#46; El tratamiento posquir&#250;rgico de los feocromocitomas y los PGL incluye una monitorizaci&#243;n hemodin&#225;mica estrecha y el tratamiento de las complicaciones posoperatorias&#44; el estudio patol&#243;gico de la muestra quir&#250;rgica&#44; la reevaluaci&#243;n del estado hormonal y&#47;o radiol&#243;gico y la planificaci&#243;n del seguimiento en funci&#243;n del riesgo de recurrencia y de malignidad&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">La cirug&#237;a representa el tratamiento de elecci&#243;n de la mayor&#237;a de los PGL abdominales y feocromocitomas&#46; La evaluaci&#243;n posoperatoria &#243;ptima&#44; que incluye la evaluaci&#243;n hemodin&#225;mica&#44; patol&#243;gica&#44; hormonal y radiol&#243;gica&#44; debe ser realizada por un equipo multidisciplinar especializado en el tratamiento de PGL&#47;feocromocitomas&#46;</p></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Surgical treatment algorithm in pheochromocytomas&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#42; Consider the retroperitoneal approach in case of previous abdominal surgery&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42; In selected cases&#44; one-stage surgery with repositioning of the patient may be considered&#46; Same approach considerations depending on the size of the lesion&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#42;&#42;&#42; Excision or ablative treatment of resectable metastases will be considered if the general situation of the patient &#40;ECOG or PS&#41; allows it&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Regarding adrenal &#8220;conservative&#8221; surgery&#44; it has not been introduced in the hospital&#44; but we believe that at this time it could be considered in the case of bilateral lesions or contralateral recurrence after previous adrenalectomy&#44; and after its discussion in the endocrine tumour board&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">LESS&#58; Laparoendoscopic Single-Site&#59; PGL&#58; paraganglioma&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Approach&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Advantages&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Transperitoneal laparoscopic aproach</td><td class="td" title="\n
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                  \t\t\t\t">PGLs&#47;pheochromocytoma &#60;6&#8722;8&#8239;cm</td><td class="td" title="\n
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                  \t\t\t\t">Compared to open surgery&#58;&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">Controversy regarding its role in large adrenal masses&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">- Lower surgical and postsurgical morbidity&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">Risk of capsule rupture</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t">- Equal success and recurrence rate&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">- Shorter hospital stay&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Retroperitoneal laparoscopic approach</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">Same indications that transperitoneal approach&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The same as transperitoneal approach</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">Reduced operative space&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Surgeon decision&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">Technically difficult in the obese patient&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 " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Open surgery</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">Pheochromocytoma&#47;PGLs &#62;6&#8722;8 cm&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">Safer control of large adrenal masses&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">Increased surgical and perioperative morbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><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">Retroperitoneal PGL&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">Possibility of additional extensive retroperitoneal lymphadenectomy&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">Increase in hospital stay&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">Robotic surgery&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">Same indications as laparoscopic surgery&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">Same as laparoscopic surgery&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">Cost increase&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 " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Less</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Same indications as laparoscopic surgery</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">Same as laparoscopic surgery&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  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Technical difficulty</td></tr><tr title="table-row"><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">Better cosmetic results&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3319338.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Surgical approaches in pheochromocytoma and abdominal paragangliomas&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0020"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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">Histological pattern&#58;&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
                  \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>- Zellballen&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>- Large or irregular cell nests&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- Pseudorosettes&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cellularity&#58;&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
                  \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>- Low &#40;&#60;150 cells per field 400x&#41;&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>- Moderate &#40;150&#8722;200 cells per field 400x&#41;&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- High &#40;&#62;250 cells per field 400x&#41;&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">2&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">Presence of comedonecrosis&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">2&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">Vascular or capsular invasion&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ki67 labelling index&#58;&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
                  \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;1&#37;&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>- 1&#8722;3&#37;&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- &#62;3&#37;&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">2&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">Catecholamine type&#58;&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
                  \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>- Epinephrine type&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>- Norepinephrine type &#40;norepinephrine &#43;&#47;- dopamine&#41;&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>- Non-functioning type&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 " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grading&#58; well differentiated &#40;0&#8722;2&#41;&#44; moderately differentiated &#40;3&#8722;6&#41; and poorly differentiated &#40;7&#8722;10&#41;&#46;</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">The higher the grade&#44; the greater the risk of metastasis&#46;</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3319340.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">GAPP SCALE &#40;Grading of Adrenal Pheocromocytoma and Paraganglioma&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p>"
        ]
      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0025"
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            "rol" => "short"
          ]
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        "tabla" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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">Large nests or diffuse growth &#40;&#62;10&#37; of tumor volumen&#41;&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">2&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">Central or confluent tumor necrosis&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">2&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">High cellularity&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">2&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">Cellular monotony&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">2&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">Tumor cell spindling&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">2&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">Mitotic figures &#62;3&#47;10 High Power Fields&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">2&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">Atypical mitotic figure&#40;s&#41;&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">2&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">Extension into adipose tissue&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">2&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">Vascular invasion&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Capsular invasion&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Profound nuclear pleomorfism&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 " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nuclear hyperchromasia&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A score greater than 4 is considered to confer an increased risk of metastasis</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">PASS SCALE &#40;Pheochromocytoma of the Adrenal Gland Scoring Scale&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p>"
        ]
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      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46;W&#46;M&#46; Lenders"
                            1 => "Q&#46;Y&#46; Duh"
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                  "host" => array:1 [
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            1 => array:3 [
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              "etiqueta" => "2"
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                  "contribucion" => array:1 [
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                      "Revista" => array:6 [
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            2 => array:3 [
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                          "etal" => false
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                      "titulo" => "Update on pheochromocytoma and paraganglioma from the SSO endocrine and head and neck disease site working group&#44; part 2 of 2&#58; perioperative management and outcomes of pheochromocytoma and paraganglioma"
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                          "autores" => array:6 [
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                            1 => "J&#46;E&#46; Phay"
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                            0 => "M&#46; Araujo-Castro"
                            1 => "R&#46; Garc&#237;a Centero"
                            2 => "M&#46;C&#46; L&#243;pez-Garc&#237;a"
                            3 => "C&#46; &#193;lvarez Escol&#225;"
                            4 => "M&#46; Calatayud Guti&#233;rrez"
                            5 => "C&#46; Blanco Carrera"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1007/s12020-021-02843-6"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;F&#46; Plouin"
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                            2 => "O&#46;M&#46; Dekkers"
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                  "host" => array:1 [
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                    0 => array:2 [
                      "titulo" => "The north american neuroendocrine tumor society consensus guideline for the diagnosis and management of neuroendocrine tumors&#58; pheochromocytoma&#44; paraganglioma&#44; and medullary thyroid cancer"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46; Chen"
                            1 => "R&#46;S&#46; Sippel"
                            2 => "M&#46;S&#46; O&#8217;Dorisio"
                            3 => "A&#46;I&#46; Vinik"
                            4 => "R&#46;V&#46; Lloyd"
                            5 => "K&#46; Pacak"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1097/MPA.0b013e3181ebb4f0"
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              "identificador" => "bib0045"
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                    0 => array:2 [
                      "titulo" => "Perioperative management during laparoscopic resection of large pheochromocytomas&#58; a single-institution retrospective study"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "H&#46; Liu"
                            1 => "B&#46; Li"
                            2 => "X&#46; Yu"
                            3 => "Y&#46; Huang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jso.25205"
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                        "tituloSerie" => "J Surg Oncol"
                        "fecha" => "2018"
                        "volumen" => "118"
                        "paginaInicial" => "709"
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              "identificador" => "bib0050"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Laparoscopic surgery for pheochromocytoma and paraganglioma removal&#58; a retrospective analysis of anaesthetic management"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Ramachandran"
                            1 => "V&#46; Rewari"
                            2 => "A&#46; Sharma"
                            3 => "R&#46; Kumar"
                            4 => "A&#46; Trikha"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2174/1573402112666160510122357"
                      "Revista" => array:6 [
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                        "fecha" => "2016"
                        "volumen" => "12"
                        "paginaInicial" => "222"
                        "paginaFinal" => "227"
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