Study design and participants
This study involved three PPGL treatment centers: 1. Nanhu Center at Shengjing Hospital of China Medical University, 2. The First Affiliated Hospital of China Medical University, and 3. Huaxiang Center at Shengjing Hospital of China Medical University. It received approval from the Research Ethics Commission of Shengjing Hospital of China Medical University (Approval No. 2018PS398K). Due to the study's retrospective nature, the need for written informed consent was exempted. Our retrospective analysis covered 979 consecutive patients who underwent surgical resection of PPGL across these centers from January 1, 2012, to October 31, 2022. All patients had a minimum follow-up period of one year.
Inclusion and exclusion criteria
Patients diagnosed with PPGL were confirmed through pathological examination. The study included those who underwent either unilateral laparoscopic or open tumor resection. These patients were in the clinical stage of localized disease and had an American Society of Anesthesiologists (ASA) score ranging from 1 to 3. Exclusion criteria were applied to patients who required conversion to laparotomy, those with a history of congenital heart disease or cardiac surgery, those affected by inherited syndromes (MEN2A/VHL/NF) or multi-focal tumors, and patients presenting tumor recurrence or metastasis at follow-up. Following these criteria, 472 patients were deemed eligible for the study. The process of patient selection is detailed in Figure 1.
Interventions
Patients exhibiting typical biochemical and radiographic indications of PPGLs underwent comprehensive preoperative medical preparation. This regimen involved administering selective or non-selective α-blockers for at least two weeks, supplemented by β-blockers for tachycardia and calcium channel blockers when necessary. Exceptions were made for patients presenting normal blood pressure and biochemical tests coupled with atypical radiographic signs of a PPGL. The protocol also recommended a high-sodium diet and increased fluid intake to counteract the blood volume contraction caused by catecholamines. The criteria for adequate preoperative preparation were a blood pressure below 130/80 mmHg and a heart rate under 90 beats per minute. All patients received general anesthesia, and the surgical procedures were carried out by experienced surgeons and anesthesiologists, ensuring high clinical proficiency.
Follow-up
In alignment with established guidelines, long-term postoperative monitoring of patients is advised. 9 We suggest conducting evaluations every six months during the initial two years, followed by annual assessments thereafter 10. Our review encompassed electronic medical records from the three involved centers, focusing on patient symptoms, signs, blood pressure, urine or plasma catecholamine levels, and imaging studies to assess for tumor recurrence or metastasis. In October 2022, a comprehensive telephone survey was conducted with all participating patients. During this interview, patients provided updates on their current health status, ongoing medications, and any new-onset cardiovascular complications. Medical records from the hospitals were used to corroborate all self-reported cardiovascular complications
Outcomes
We recorded patient demographics, including age, sex, Body Mass Index (BMI), comorbidities such as ASA scores, diabetes mellitus, and coronary artery disease (CAD) or stroke. Additionally, family history of hypertension, PPGL classification, and preoperative data like tumor size, 24-hour urine VMA/MN/NMN levels, and LVEF were considered. Intraoperative details, including the surgical approach, instances of HDI, surgery duration, and blood loss, were also captured. Short-term postoperative data focused on cardiovascular complications and hospital stay length, while long-term follow-up data encompassed the duration, persistent hypertension, and long-term cardiovascular complications.
Low LVEF was less than 50%, indicating left ventricular systolic dysfunction 11. Cardiovascular complications were broadly defined to include incidences or deaths caused by coronary artery disease, myocardial infarction, arrhythmia, heart failure, stroke, and pulmonary embolism or deep vein thrombosis 12,13. Long-term cardiovascular complications were specified as new onset issues emerging at least one-year post-surgery for PPGLs. Intraoperative HDI was identified by extremely high or low blood pressure during surgery, defined as a systolic blood pressure (SBP) ≥ 200 mm Hg or <80 mm Hg, or mean arterial pressure <60 mm Hg 14,15. Persistent hypertension post-surgery was defined as a sustained blood pressure of 140/90 mm Hg or higher, including those requiring ongoing anti-hypertensive medication during follow-up.
Statistical analysis
Statistical analyses in this study were conducted using SPSS version 26.0. We presented continuous variables as means with standard deviations, medians, or interquartile ranges, depending on their distribution. Categorical variables were shown as counts and percentages. The normality of the data was assessed using the Kolmogorov-Smirnov test, with normally distributed data presented as mean ± Standard Deviation (SD) and non-normally distributed (nonparametric) data as medians with interquartile ranges (IQRs). We employed the Chi-square test for categorical variable comparisons, while continuous variables were compared using either the t-test or the Mann-Whitney U test based on their distribution. A multivariate binary logistic regression model included variables deemed clinically significant or those showing a P value < 0.1 in univariate analysis. Statistical significance was established at a two-tailed P value of less than 0.05.