Predictors of postoperative recurrence of pheochromocytoma: A monocentric study

doi:10.21203/rs.3.rs-3310366/v1

Background

To discuss the risk factors affecting the recurrence of pheochromocytoma after surgery.

Methods

We retrospectively reviewed patients who were hospitalized and underwent surgery for PCC between January 2012 and December 2020 at Chinese PLA General Hospital. Inclusion criteria were pathological diagnosis of PCC and availability of follow up.

Results

In total, 451 patients met the inclusion criteria. The average age was 45.89 years, and the median tumor diameter was 5.75 cm. The mean recurrence time was 34.24 months. Of the 451 patients receiving surgery, there were 35 recurrent cases (7.85%). The univariate test showed that age, hypertension, history of PCC recurrence, Ki-67 index ≥ 5, bilateral tumor, duration of phenazopyridine administration, DBP at admission, open operation, intraoperative HR minimum, intraoperative times of HR over 120, times of instability, and intraoperative bleeding were associated with recurrence after radical surgery. Multivariate COX regression analysis of age (HR(hazard ratio) 0.95), hypertension (HR 7.14), history of PCC recurrence (HR 69.35), family history of hypertension (HR 16.30), bilateral tumor (HR 7.38), tumor size (HR 1.05), times of instability (HR 114.91) and length of instability in minutes (HR 1.12) were the independent influences on recurrence after pheochromocytoma resection.

Conclusions

Age, hypertension, history of PCC recurrence, family history of hypertension, bilateral tumor, tumor size, intraoperative times of instability, and intraoperative instability minutes were independent influences on recurrence after pheochromocytoma resection.

Pheochromocytoma

Recurrence

Risk factors

Epidemiology

Pheochromocytomas are tumors originating from chromophores in the adrenal medulla and account for 80–85% of pheochromocytomas and paragangliomas.[1] They have catecholamine hormonal activity and mainly synthesize, secrete and release large amounts of CA, such as NE, E and DA, causing a series of clinical syndromes such as increased blood pressure and metabolic changes, causing serious complications in the heart, brain, kidneys and blood vessels, and even becoming a major cause of death in patients. In the 4th edition of the 2017 classification of endocrine tumors,[2] the WHO suggests that all pheochromocytomas/paragangliomas have metastatic potential and recommends that pheochromocytomas/paragangliomas be classified as metastatic and nonmetastatic, rather than malignant and benign.[3] The risk factors for recurrence or metastasis of PCC have been discussed only rarely, and the results are also controversial. Most articles[4–10] reported that age, gene mutation and tumor size are independent risk factors, but these studies included limited samples. In this study, we investigated the differences in clinical parameters between patients with and without recurrence by following up with pheochromocytoma resection patients in our center, which may enable urologists to accurately counsel urological patients when predicting postoperative recurrence after resection of PCC.

2.1 Objectives

The primary objective of this review was to identify the risk factors affecting the recurrence of pheochromocytoma after surgery.

2.2 Patient selection

Patients who were hospitalized and underwent tumor resection for PCC at our center from January 2012 to December 2020 were selected. Inclusion criteria were as follows: (1) clear diagnosis of PCC by postoperative pathology; (2) cooperation in the follow-up process; and (3) postoperative pathology suggests complete removal of the tumor. Exclusion criteria were as follows: (1) did not receive primary foci surgery; (2) incomplete medical records; and (3) lost in the follow-up process. In total, 451 patients met the inclusion criteria.

2.3 Methods

(1) Data collection included the following: demographics, clinical and pathological characteristics [age, sex, body mass index (BMI), comorbidities (hypertension, diabetes), history of pheochromocytoma recurrence, family history of hypertension, tumor size, Ki-67 index, preoperative NE, E, DA, tumor side], patient perioperative data [daily preoperative phenoxybenzamine dose, duration of phenazopyridine administration, dos*time/weight, SBP at admission, DBP at admission, operation mode, surgical approach, postoperative SBP, postoperative DBP, HR max, HR min, HR range, times of HR over 120, one-time HR range, SBP max, SBP min, SBP range, one-time SBP range, DBP max, DBP min, DBP range, one-time DBP range, MAP max, MAP min, MAP range, times and duration of instability in intraoperative BP and HR (instability in intraoperative BP and HR were measured by scoring the number and time periods of episodes that the SBP was higher than 180 mmHg, SBP was higher than 130% of the SBP at admission, DBP was lower than 80 mmHg or the DBP was lower than 70% of the DBP at admission or the heart rate was over 120 bpm), intraoperative bleeding. For the purposes of this study, the main outcome measure was recurrence, defined as tumor reappearance (structural recurrence seen on imaging), including local site and/or distant metastasis.[7] Patients' postoperative status was obtained based on clinical follow-up or telephone follow-up. To determine the clinical stage and the presence of nearby or distant metastases, all patients underwent preoperative imaging, such as MRI, CT or ultrasound. With an initial visit between 6 and 12 months, followed by semiannual or annual visits, all patients were postoperatively followed up for more than two years. Each visit included radiographic evaluation, and some visits included laboratory examinations. (3) Recurrence criteria included the following: reappearance of new PCC lesions at the original tumor site after complete resection of the primary lesion.

2.4 Statistical analysis

SPSS 26.0 statistical software was used for data analysis. Quantitative variables conformed to a normal distribution and were expressed as (x ± s), and the independent samples t test was used for comparison between groups. Quantitative variables did not conform to a normal distribution and were expressed as M(Q1, Q3), and the Wilcoxon rank sum test was used for comparisons between groups. The χ2 test was used to compare the proportion of occurrence of qualitative data between groups. Finally, we selected 12 sets of data for univariate and multivariable COX regression analysis to obtain Exp(B). Recurrence was treated as a time-dependent variable. P values < 0.05 were considered significant.

3.1 Baseline characteristics of the cohort and percentage of recurrences

The age of the 451 patients after pheochromocytoma resection was 45.89 ± 14.417 years, among which 229 (51.9%) were male and 222 (49.20%) were female. The proportion of patients with hypertension was 55.21%, and the median tumor size/diameter was 5.75 cm. During the follow-up period, there were 35 recurrent cases (7.85%) and two deaths, one from natural causes and one from lymphoma, neither of which was significantly associated with pheochromocytoma. The mean recurrence time was 34.24 months.

3.2 Characteristics of the demographics, clinical and pathological profiles of patients with pheochromocytoma after resection

After statistical data and analysis, patients presenting with postoperative recurrence were generally younger [36.54 ± 14.41 years compared to 47.61 ± 0.83, p < 0.001], had a higher proportion of combined hypertensive symptoms [26 cases (10.4%) compared to 9 cases (4.5%), p = 0.018] and had a higher proportion of previous history of pheochromocytoma recurrence [8 cases (42.1%) versus 27 cases (6.25%), p < 0.001]. Patients who presented with postoperative recurrence were more likely to have bilateral tumors [7 (17.5%) versus 28 (6.8%), p = 0.036]. Patients who presented with postoperative recurrence were more likely to have a Ki-67 index ≥ 5 [11 (31.43%) versus 12 (34.29%), p = 0.036]. The tumor size was not different between the two groups (Table 1).

3.3 Characteristics of perioperative data in patients after pheochromocytoma resection

After statistical data and analysis, patients presenting with postoperative recurrence generally had a longer duration of phenazopyridine administration [21.24 ± 12.77 days versus 27.55 ± 16.35 days, p = 0.044] and higher diastolic blood pressure at admission [81.00 (77.25,92.25) mmHg versus 80.00 (74.00,90.00) mmHg, p = 0.046]. Patients who underwent open surgery had a higher postoperative recurrence rate than those who underwent laparoscopic and robotic surgery [7 (21.9%) compared to 20 (6.3%) and 8 (8%), p = 0.026]. Patients presenting with postoperative recurrence generally had a lower HR minimum heart rate [65.22 ± 13.88 days versus 58.09 ± 8.74 days, p ≤ 0.001], a higher proportion of times of HR over 120 ≥ 6 [5 cases (29.41%) compared to 30 cases (6.91%), p = 0.018], a higher proportion of times of instability ≥ 8 [4 cases (11.43%) compared to 5 cases (1.44%), p = 0.018], and a higher intraoperative bleeding volume [175.0 (100.0,450.0) compared to 100.0 (50.0,275.0), p = 0.018]. However, there was no significant difference in recurrence rates between patients who opted for laparoscopy and those who opted for robotics (Table 2).

3.4 Univariate and multivariate-factors COX analyses

The criteria of these 12 datasets were statistically significant or considered potentially clinically significant, and the influence of human factors was removed as much as possible. These variables were investigated using univariate and multivariate COX analyses for predicting recurrence after radical surgery. Age (hazard ratio 0.95, p = 0.001), hypertension (hazard ratio 7.14, p = 0.029), history of PCC recurrence (hazard ratio 69.35, p < 0.001), family history of hypertension (hazard ratio 16.30, p < 0.001), bilateral tumor (hazard ratio 7.38, p = 0.045), tumor size (hazard ratio 1.05, p = 0.031), intraoperative times of instability (hazard ratio 114.91, p = 0.034), and intraoperative instability minutes (hazard ratio 1.12, p = 0.025) were identified as independent prognostic factors for recurrence after radical surgery (Table 3).

3.6 K-M Survival Analysis:

We tried to use ROC curve analysis to show the Joden index of continuous variables in independent influencing factors and locate the diagnostic critical value. From the analysis, we obtained an AUC for age of 0.692 and a diagnostic threshold of 41.5 years. The AUC for tumor size was 0.489, with a diagnostic threshold of 11.25 cm. The AUC for intraoperative instability minutes was 0.528, with a diagnostic threshold of 12.5 min (Figure S1).

The survival curve is drawn according to K-M curve analysis of classified variables in independent influencing factors and continuous variables treated with diagnostic critical values. At the same time, the log-rank test was used to evaluate survival differences. By analysis, we derived significant differences in survival curves for age (< 41.5 years) (p = 0.0003), combined hypertension (p = 0.014), previous history of recurrence (p < 0.0001), bilateral tumors (p = 0.0037), tumor size (≥ 11.25 cm) (p = 0.0032), and times of instability ≥ 8 (p = 00.13). We found no significant differences in survival curves for instability minutes (≥ 12.5 min) (p = 0.33) or family history of hypertension (p = 0.2) (Fig. 1).

In conclusion, we found that the number of recurrence patients was 35 (7.8%), which was matched with other research (between 1% and 34%, median 6%).[11, 12] The independent samples test showed that age, hypertension, history of PCC recurrence, Ki-67 index ≥ 5, bilateral tumor, duration of phenazopyridine administration, DBP at admission, open operation, intraoperative HR minimum, intraoperative times of HR over 120, times of instability, and intraoperative bleeding were associated with recurrence after radical surgery. The mutivariate COX analyses showed that age, hypertension, history of PCC recurrence, family history of hypertension, bilateral tumor, tumor size, intraoperative times of instability, and intraoperative instability minutes were independent influences on recurrence after pheochromocytoma resection. The result was similar to those of other articles.[1, 4, 5, 9, 11–17]

According to a 2016 meta-analysis,[12] there was a negative correlation between age and recurrence rate, but it lost its statistical significance in multivariate analysis. This was different from our study, as the age in the multivariate Cox analysis was still less than 0.001. Some research[1, 4, 5, 9, 13–17] showed that younger patients were more likely to experience recurrence, and others[8, 10] said that elderly patients were more likely to experience recurrence. Pediatric patients made up approximately 10% of cases of PCC, which could occur at any age but was more common in those in their 40 s and 50 s. According to the literature,[13, 17–19] 70% of these patients had germline mutations with a high genetic propensity. This study may provide evidence of our results regarding age, in which younger patients had more germline mutations in tumors that made recurrence more likely.

PCCs are rare tumors with an estimated annual incidence of 3 per 1 million[20, 21]. However, the percentage of pheochromocytomas in the hypertensive population is between 0.1% and 0.6%[22]. According to our statistics, patients who have combined symptoms of hypertension are more likely to experience recurrence after surgery. Additionally, the higher the patient's blood pressure (SBP at admission, DBP at admission and intraoperative MAP maximum), the higher the probability of postoperative recurrence. Some research[10] showed the same result.

Evidence to date[23] suggests that more than 40% of patients with pheochromocytoma or paraganglioma carry germline mutations, regardless of age at onset and family history. We statistically found a significant association between recurrence and family history of hypertension in our patients by multivariate analyses, which was also showed by a previous study,[10] which may prove that pheochromocytomas were indeed affected by family inheritance.

Research[10, 24] showed that in addition to patients at risk of hereditary pheochromocytoma, patients with previously removed tumors are another high-risk group, which agreed with our results.

Bilateral PCCs more easily lead to major functional morbidity and recurrence, even after surgical treatment.[1, 10, 13–16, 21] In our study, we also found that bilateral tumors were associated with recurrence.

In this study, we found that tumor size was not associated with recurrence in univariate analysis but was significantly associated with recurrence in multivariate analysis. In most studies,[5, 6, 9, 11] tumor size was always an independent predictor of recurrence. The reasons for the discrepancy between univariate and multivariate analyses could be manifold. The average tumor size of patients who first came to the center was 5.75 cm, which meant that half of the patients were past the T2 stage. Of course, these data were larger than the guideline/literature average (between 2.3–2.7 cm, median 48 mm). [12] Second, the reason why tumor size became an influencing factor may be related to the surgical method and the doctor's surgical level. Large-diameter PCC resection tested the doctor's surgical level, and the center's doctor's surgical technology was mature, which could ensure that the tumor was removed as cleanly as possible. Additionally, research[4, 6, 7, 25] has shown that pheochromocytomas identified by screening for Von Hippel‒Lindau disease are smaller and less functional than sporadic pheochromocytomas. This may also account for the lack of a significant correlation between our tumor size and recurrence in the independent sample’s T test.

In our results regarding the intraoperative characteristics, not only the times of instability but also the duration of instability in minutes were independent influencing factors. There are few articles on perioperative statistics. Most of the articles in this part believe that blood pressure drop (max to min) is closely related to recurrence, and some articles[8] thought that blood pressure instability could increase the occurrence of postoperative complications and death, which may explain our results.

Due to many limitations, the present results should be evaluated with caution. The study was a single-center, retrospective observational analysis. Second, metanephrines were not obtained post-op to confirm complete resection. Third, the patients were not evaluated for germline mutations. Forth, recurrence was not based on biochemical values. Last, the study included patients who had surgery less than 5 years prior to the study, and some of them had tumors that may not yet recurred.

Age, hypertension, history of PCC recurrence, family history of hypertension, bilateral tumor, tumor size, intraoperative times of instability, and intraoperative instability minutes were independent influences on recurrence after pheochromocytoma resection. Ki-67 index ≥ 5, duration of phenazopyridine administration, DBP at admission, open operation, intraoperative HR minimum, intraoperative times of HR over 120, and intraoperative bleeding were associated with recurrence after radical surgery. Information from this study will enable urologists to accurately counsel urological patients when predicting postoperative recurrence after resection of PCC.

Ethics approval and consent to participate

The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Human Ethics Committee of Chinese PLA general hospital licensing committee. Written informed consent was obtained from individual or guardian participants.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated and analysed during the current study are not publicly available due [REASON WHY DATA ARE NOT PUBLIC] but are available from the corresponding author on reasonable request.

Competing interests

The authors have no conflicts of interest to declare.

Funding

The present work was financially supported by the National Natural Science Foundation of China (No. 81900718), and PLA General Hospital "National Science Fund for Outstanding Young Scholars" cultivation Foundation (No.202002)

Authors' contributions

Jia Yuqi: Data curation

Lai Dong: Writing - review & editing, Data curation, Formal analysis

Li Xintao: Writing - review & editing, Formal analysis, Manuscript editing

Li Zhuoran: Data curation, Formal analysis, Writing - original draft

Luo Jin: Data curation

Ma Xin: Supervision

Tang Lu: Formal analysis

Wang Baojun: Conceptualization, Manuscript editing, Project administration, Writing - review & editing

Zhang Xu: Supervision

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Table 1. Patient demographics and clinical and pathological characteristics

Variables	Overall	No-recurrence (n=416)	Recurrence (n=35)	P value
age(year)	45.89±14.42	36.54±14.41	47.61±0.83	<0.001
Sex				0.543
male	229(50.80%)	209(50.20%)	20(57.1%)
female	222(49.20%)	207(49.80%)	15(42.9%)
BMI	24.49±10.98	23.57±13.43	23.56±4.60	0.604
Hypertension				0.018
Present	249(55.20%)	223(53.60%)	26(74.30%)
Absent	202(44.80%)	193(46.40%)	9(25.70%)
Diabetes				0.643
Present	118(26.20%)	110(26.40%)	8(22.90%)
Absent	333(73.80%)	306(73.60%)	27(77.10%)
History of PCC recurrence				<0.001
Present	19(4.20%)	11(2.60%)	8(22.90%)
Absent	432(95.80%)	405(97.40%)	27(77.10%)
Family history of hypertension				0.098
Present	173(38.40%)	155(37.70%)	18(51.40%)
Absent	278(61.60%)	261(62.30%)	17(48.60%)
tumor size(cm)	5.0(3.5,7.0)	5.0(3.5,7.0)	6.0(5.8,6.8)	0.447
Ki-67 index				0.031
<5	225(49.89%)	213(51.20%)	12(34.29%)
≥5	89(19.73%)	78(18.75%)	11(31.43%)
Unknown	137(30.38%)	125(30.05%)	12(34.29%)
Preoperative NE	277.9(111.3,556.2)	289.3(86.1,570.5)	250.1(178.6,739.8)	0.523
Preoperative E	41.7(14.7,121.9)	37.7(11.0,102.7)	80.9(29.4,164.9)	0.503
Preoperative DA	419.6(281.4,681.9)	395.3(277.4,654.9)	524.1(441.7,735.6)	0.124
tumor side				0.036
left	195(43.20%)	182(43.80%)	14(48.10%)
right	215(56.80%)	201(56.20%)	14(51.90%)
Bilateral	33(8.90%)	25(7.90%)	7(20.00%)
Unclassified	8(1.8%)	8(1.9%)	0

Table 2. Patient perioperative characteristics

Variables	Overall		No-recurrence (n=416)	Recurrence (n=35)	*t/u/x²*	P Value
Daily preoperative phenoxybenzamine dose (ml)		20.0(15.0,35.0)	20.0(12.5,35.0)	17.5(10.6,25.0)	-0.825	0.409
Duration of phenazopyridine administration (day)	26.0±15.7		27.6±16.4	21.2±12.8	2.021	0.044
*Dostime/weight**	7.1(4.1,13.3)		7.5(4.4,13.1)	5.7(3.9,9.5)	-1.364	0.173
SBP at admission	130.0(120.0,142.5)		130.0(120.0,150.0)	127.0(120.0,140.0)	-0.714	0.475
DBP at admission	80.0(70.0,90.0)		80.0(70.0,90.0)	85.0(70.0,90.0)	-2.217	0.027
Operation mode					7.267	0.026
Open	32(7.10%)		25(6.00%)	7(20.00%)
Laparoscopic	319(70.70%)		299(71.90%)	20(57.10%)
Robotic	100(22.20%)		92(22.10%)	8(22.90%)
Surgical approach					1.467	0.226
open	32(7.10%)		25(6.00%)	7(20.00%)
Transperitoneal	109(26.00%)		99(25.30%)	10(35.70%)
Retroperitoneal	310(74.00%)		292(74.70%)	18(64.30%)
Postoperative SBP (mmHg)	120.0(110.0,130.0)		120.0(106.3,137.5)	120.0(110.0,135.0)	-0.406	0.684
Postoperative DBP (mmHg)	70.0(60.0,80.0)		70.0(60.0,80.0)	70.0(60.3,87.5)	-0.616	0.538
HR max	106.67 ± 17.40		106.43 ± 16.54	107.57 ± 20.58	-0.345	0.734
HR min	59.58 ± 10.40		58.09 ± 8.74	65.22 ± 13.88	-3.718	<0.001
HR range	47.08 ± 16.59		48.34 ± 16.35	42.35 ± 16.89	1.896	0.051
Times of HR over 120					5.566	0.018
<6	434(96.23%)		404 (97.12%)	30 (85.72%)
≥6	17(3.77%)		12 (2.88%)	5 (14.28%)
One-time HR range	24.06 ± 12.34		23.85 ± 12.57	24.85 ± 11.58	-0.351	0.674
SBP max	163.01 ± 24.43		163.00 ± 24.48	163.09 ± 24.38	-0.020	0.984
SBP min	95.54 ± 13.94		95.50 ± 13.49	95.96 ± 17.77	-0.171	0.856
SBP range	66.88 ± 27.73		66.85 ± 27.23	67.13 ± 32.45	-0.061	0.955
One-time SBP range	45.73 ± 24.71		46.04 ± 23.77	42.94 ± 32.25	0.719	0.489
DBP max	90.10 ± 13.10		89.97 ± 13.23	91.25 ± 12.06	-0.543	0.589
DBP min	53.77 ± 8.62		53.68 ± 8.35	54.63 ± 10.84	-0.617	0.540
DBP range	35.49 ± 14.47		35.37 ± 14.37	36.62 ± 15.56	-0.476	0.633
One-time DBP range	22.88 ± 11.46		23.02 ± 11.41	21.62 ± 12.04	0.674	0.498
MAP max	110.44 ± 22.55		110.03 ± 23.26	114.22 ± 14.19	-1.027	0.305
MAP min	66.95 ± 14.02		66.62 ± 14.13	70.04 ± 12.69	-1.353	0.177
MAP range	43.49 ± 17.89		43.41 ± 17.66	44.18 ± 20.22	-0.234	0.815
Times of instability					8.648	0.003
<8	442(98.00%)		411 (98.56%)	31 (88.57%)
≥8	9(2.00%)		5 (1.44%)	4 (11.43%)
Length of instability in minutes	16.94 ± 25.46		16.30 ± 22.99	22.59 ± 41.65	-1.364	0.173
Intraoperative bleeding (ml)	100.0(50.0,312.5)		100.0(50.0,275.0)	175.0(100.0,450.0)	-2.105	0.035

Table 3. Univariate and multivariate analyses

Variables	Univariate analyses		Multivariate analyses
	HR(95% CI)	P value		HR(95% CI)	P value
Age	0.95 (0.92, 0.97)	<0.001		0.95 (0.91, 0.99)	0.001
Sex(female)	0.79 (0.39, 1.64)	0.532
BMI	0.96 (0.88, 1.04)	0.310
Drug dosage per day	0.99 (0.96, 1.02)	0.626
Length of medication	0.96(0.92-0.99)	0.012		1.01(0.91,1.12)	0.788
Hypertension	2.36 (1.18, 5.74)	0.018		7.14 (1.23,41.54)	0.029
Diabetes	0.71 (0.29, 1.73)	0.448
History of PCC recurrence	10.20 (4.35, 23.91)	<0.001		69.35(7.97,603.73)	<0.001
Family history of hypertension	1.77(0.87,3.64)	0.118		16.30(1.55,251.8)	<0.001
Bilateral tumor	5.25 (2.23, 12.37)	0.001		7.38(1.04,52.24)	0.045
Left or right side	0.79 (0.35, 1.79)	0.568
Ki-67≥5	1.07(1.00,1.14)	0.045		26.70(0.13,5519.68)	0.227
SBP at admission	0.88(0.79,1.01)	0.339
DBP at admission	1.03 (1.01, 1.06)	0.014
Surgery approach (open or not)	0.31 (0.13, 0.76)	0.011		1.00(0.07,12.64)	0.999
Surgery approach (laparoscopic/robotic)	1.36 (0.53, 3.48)	0.519
Surgery trans (transperitoneal/retroperitoneal)	0.56 (0.24, 1.33)	0.191
Tumor size	1.06(0.92,1.21)	0.436		1.65(1.04,2.60)	0.031
times of HR over 120 ≥6	4.32(1.28,14.65)	0.019		121.43(0.03,584419.65)	0.267
Times of instability ≥8	5.69(1.72,18.88)	0.005		114.91(1.68,7870.89)	0.034
Length of instability in minutes	1.01(1.00,1.02)	0.121		1.12(1.02,1.25)	0.025
HR range	0.99(0.97,1.01)	0.376
One-time HR range	1.02(0.99,1.05)	0.134
SBP range	1.00(0.99,1.02)	0.201
One-time SBP range	1.00(0.99,1.01)	0.181
DBP range	1.01(0.99,1.04)	0.294
One-time DBP range	1.00(0.97,1.03)	0.969
MAP range	1.01(0.99,1.03)	0.469

No competing interests reported.

Supplementaryfigure.docx

Predictors of postoperative recurrence of pheochromocytoma: A monocentric study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusions

Figures

1. Background

2. Evidence acquisition

2.1 Objectives

2.2 Patient selection

2.3 Methods

2.4 Statistical analysis

3 Results

3.1 Baseline characteristics of the cohort and percentage of recurrences

3.2 Characteristics of the demographics, clinical and pathological profiles of patients with pheochromocytoma after resection

3.3 Characteristics of perioperative data in patients after pheochromocytoma resection

3.4 Univariate and multivariate-factors COX analyses

3.6 K-M Survival Analysis:

4 Discussion

5 Conclusions

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1