Is there a need for preoperative α-blocker in patients missed preoperative diagnosis of extra-adrenal retroperitoneal paraganglioma undergoing paraganglioma resection? A retrospective study of 167 cases at a single center

Background Preoperative α-adrenergic blockade is believed to decrease perioperative risks and mortality in adrenal pheochromocytoma surgeries. The aim of this study is to evaluate the effects of the preoperative α-adrenergic blockade on patients’ outcomes in extra-adrenal retroperitoneal paraganglioma surgeries. Methods We searched our clinical database for the diagnosis extra-adrenal retroperitoneal paraganglioma by postoperative histopathology in the General Hospital of People’s Liberation Army from 2000 till 2017. And we recorded preoperative status of patients, preoperative medication preparation, intraoperative and postoperative cardiovascular events, intake and output, length of stay in ICU, length of hospital stay, and short time outcomes. Results The intraoperative morbidity of heart rate elevation and highest heart rate were higher in patients undergoing tumor manipulation with preoperative α-adrenergic blockade than those without (P<0.05), while there were no significant differences in intraoperative morbidity of blood pressure elevation and SAP decreased following tumorectomy in these two groups (P>0.05). There were no significant differences in postoperative complications and outcomes (P>0.05). Conclusion Under the current medical techniques, either with or without preoperative medicine, resection of extra-adrenal retroperitoneal paraganglioma could be carried out successfully.

7 anti-hypertensive drugs, particularly phentolamine, esmolol and sodium nitroprusside to normalize the intraoperative hemodynamics (P < 0.05). (Figure 1) Surgical outcomes As shown in Table 3, there were no differences in the total duration of hospital stay, postoperative stay and ICU stay (P > 0.05). However, the patients pretreated with α-blockers stayed longer at the hospital before operation than those without preoperative α-blockers (10.0(12.0) days vs. 6.5(5) days, P < 0.05). One patient without preoperative α-blockers died the first day after surgery due to hemorrhagic shock in the ICU after uncontrolled intraoperative massive hemorrhage. Another patient without preoperative α-blockers died the third day after surgery for regurgitation and aspiration. There were no differences in postoperative complications and outcomes between the two groups.

Subgroup analysis
When compared with patients without preoperative α-adrenergic blockade, the patients taking other preoperative hypotensors and without any preoperative hypotensive drugs experienced the same intraoperative and postoperative circulation changing and had the same outcomes ( Table 4).

Discussion
This is the first large-scale retrospective study of patients with extra-adrenal retroperitoneal paraganglioma, most of whom were undiagnosed properatively. And our research revealed that paraganglioma resection could be carried out successfully without preoperative α-blocker in patients of omission diagnosis of paraganglioma preoperatively.
Serials of studies show that, about 80% to 85% of pheochromocytoma are located in adrenal medulla, which are called chromaffinoma or pheochromocytoma, whilst 15% to 20% are extra-adrenal, which are called paraganglioma and usually located close to the sympathetic chain, such as in the head and neck, thoracic cavity, and retroperitoneal cavity [11][12][13]. Extra-adrenal retroperitoneal paraganglioma, with no prominent clinical manifestations like headache, perspiration, and palpitations resulting from the release of catecholamine, was prone to be misdiagnosed as other retroperitoneal masses [14][15][16]. Compared with adrenal pheochromocytoma, extra-adrenal retroperitoneal paraganglioma has some significant characteristics, such as high misdiagnosis rate, complicated anatomic structure, etc [17,18]. Regarding the characteristics of extra-adrenal retroperitoneal paraganglioma, most of our patients had not manifested typical clinical symptoms of catecholamine release, so that surgeons had not been aware of extra-adrenal retroperitoneal paraganglioma which resulted in most of our patients having no preoperative medicines.
Perioperative hemodynamic instability was believed to increase the perioperative mortality and morbidity [19]. Lacking evidence from randomized controlled clinical studies, a lot of retrospective studies and institutional experience suggested paraganglioma patients must take preoperative α-blocker in order to reduce perioperative hemodynamic instability [20][21][22][23].
Conversely, some studies showed patients would undergo safe surgical procedure without preoperative α-blocking agents [7,24]. Boutros et al. reported that all the 29 patients in their series without using preoperative α-adrenergic blockade survived and were discharged from hospital without clinical evidence of cardiovascular complications and proved that patients with pheochromocytoma could undergo successful surgery without preoperative profound and long-lasting alpha adrenergic blockade. All their patients were confirmed preoperatively and infused with sodium nitroprusside and nitroglycerin alone or in combination intraoperatively [25].
Similarly, Lentchener et al. reported that high preoperative SAP was not indicative of intra-and postoperative hemodynamic instability with no regard to the administration of preoperative hypotensive drugs [26]. In our study, 29 patents who were suffered from hypertension in the group without preoperative α-adrenergic blockade took β-blockers, calcium channel blocker and angiotensin-converting enzyme inhibitors to normalize the blood pressure, like metoprolol, nifedipine, nimodipine and captopril and so forth, alone or in combination. Under the subgroup analysis, the intraoperative and postoperative circumstances of the patients with antihypertensive drugs in group without preoperative α-blocker were same when compared with the patients with preoperative α-blocker. It seemed the other kind types of hypotensors not only α-adrenergic blockade could be used safely as the preoperative medicine for extra-adrenal retroperitoneal paraganglioma. The patients with α-blocker had prolonged hospital stay especial preoperative stay for normalizing the preoperative blood pressure according to the routine recommendation to take preoperative α-blocker at least for 2 weeks, and could induce intraoperative tachycardia.
All paraganglioma were believed to synthesize and store catecholamine, and functional tumors were defined as having elevated urine or serum catecholamine levels attributed to the presence of tumor [27]. Although our study had some limitations in that none of our patients had intraoperative blood serum catecholamine assay test, about 40% patients had experienced hemodynamic instabilities including elevated blood pressure and heart rate during tumor manipulation. Therefore we can only assume those tumors with intraoperative hemodynamic instabilities were functional paraganglioma. Tauzin

Conclusion
In conclusion, our findings demonstrated that most of extra-adrenal retroperitoneal paraganglioma could experience intraoperative hemodynamic instabilities, whether preoperative α-blocker was given or not. Moreover, ensured by current surgical approaches, anesthesia skills, monitor technologies and cardiovascular drugs, patients who were missed preoperative diagnosis of extra-adrenal retroperitoneal paraganglioma could undergo surgery successfully and safely without preoperative α-blocker.