Trends of surgical treatment and enhanced recovery after surgery (ERAS) application for adrenal tumors: An 11-year observational study based on electronic medical record

Abstract

Background: Adrenal tumor is a common condition that often requires adrenalectomy. The objective of this study is to compare the safety and implementation of the enhanced recovery after surgery (ERAS) among patients who received open, laparoscopic and robotic-assisted operation. The impact of ERAS on health economics was also preliminarily evaluated.

Methods: This is a retrospective study using the electronic medical records of patients with adrenal tumor at the University of Hong Kong-Shenzhen Hospital between January 2013 and December 2023. All the patients received partial or total adrenalectomy via different surgical approaches.

Results: A total of 254 participants were included in our study. Among them, 229 (90.2%) received laparoscopic adrenalectomy, 12 (4.7%) received robotic-assisted operation, and 13 (5.1%) received open surgery. The majority of the patients' costs (n = 200, 78.7%) were covered by national health insurance in China. The proportion of robotic surgery increased significantly over time (p < 0.001). Laparoscopic surgery showed significantly shorter operating time and less bleeding than open surgery (p < 0.001). Implementation of ERAS after surgery increased from 3% in 2013–2015 to 46% in 2022–2023 following the 4N protocol (no drainage, no antibiotics, no opioid analgesia, and no intravenous fluids). The out-of-pocket expenses for patients decreased from CNY 11 700 in 2013 to CNY 2700 in 2023.

Conclusion: The proportion of ERAS has increased. Despite increased total expenses, the out-of-pocket expenses for patients have significantly decreased over time via implementation of the ERAS approach.

Graphical abstract

Keywords

adrenal / complication / enhanced recovery after surgery / health economics / laparoscopic / robotic / surgery

1 INTRODUCTION

Adrenal tumor is a common disease in the population. The prevalence of adrenal tumor is 1.4% in Chinese population, and 69.3% of which are nonfunctioning adenoma[1]. According to pathology, adrenal tumor can be classified into different types including cortical adenoma, pheochromocytoma, lipoma, ganglioneuroblastoma, hyperplasia, and so forth[2]. The proportions of hyperaldosteronism and hypercortisolism in patients with adrenal incidentalomas are 1%–4% and 5%–12%, respectively[3–5]. Among them, 30%–35% of patients may have functional cortisol secretion[5]. Another important subtype of adrenal tumor is pheochromocytomas which accounts for 0.8%–8% of a total number of adrenal tumors[4,6].

Surgical intervention is one of the effective therapies for adrenal tumors. Nearly 3% of the patients received surgical treatment eventually[7]. In the United States, the laparoscopic (57%), robotic (26%), and open (17%) adrenalectomy are commonly applied[8]. Compared with open surgery, the laparoscopic approach may reduce the demand for analgesics, shorten the length of stay and recovery time[9]. On the other hand, instability of the operating field and limited range of movement are inherent flaws of laparoscopy[10]. Robotic surgery could provide more flexible movements, more precision and elimination of the surgeon's tremor[11]. To date, pros and cons of robotic or laparoscopic adrenalectomy remain controversial[12–14]. Nevertheless, either of these minimally invasive approaches has improved the postoperative recovery greatly.

In recent years, enhanced recovery after surgery (ERAS) protocols have become popular in postoperative management. ERAS is a multimodal perioperative care pathway designed to achieve early recovery after surgery[15]. It may also ensure the organs’ functions and reduce the stress response of para-operation. Therefore, ERAS always involves a series of management steps from preoperative preparation to postoperative management[15]. In surgical treatment for adrenal tumor, ERAS may involve the para-operative endocrine management, intra-operational systematic support, as well as postoperative recovery. In primary aldosteronism, ERAS was reported to shorten hospital stays and reduce the use of analgesics after surgery[16].

In this study, we present the trends of surgical treatment for adrenal tumor in our medical center, a tertiary hospital in southern China. We also aim to evaluate the implementation of ERAS among these patients. In our medical center, the key elements of ERAS for adrenal tumors include 4N (no drain tubes, no antibiotics, no opioid analgesia use, and no intravenous fluids).

2 METHODS

2.1 Study setting and participants

Data of this study were retrospectively retrieved from the electronic medical records system in the University of Hong Kong-Shenzhen Hospital between January 1, 2013 and December 31, 2023. Patients were included in this study if they: (1) with a functional or pathologic diagnosis of adrenal tumor; and (2) undergoing any type of the below surgical methods: laparoscopic, robotic and open operation.

2.2 Outcomes of interest

The primary outcome is the ERAS implementation, including four key elements (4N): no drain tube, no antibiotics, no opioid analgesia use, and no intravenous fluid. The implementation of these elements was evaluated and recorded by the nurse. No drain tube was defined as no postoperative retention of a surgical drain. No antibiotic was known as no use of prophylaxis and postoperative antibiotic. No opioid analgesia use was considered as no use of opioid analgesia after surgery. No intravenous fluid was regarded as no extra fluid infusion during the perioperative period.

Secondary outcomes include surgical complications and health economics. Surgical complications were recorded in detail, such as hemorrhage, fever, infection, and were graded as either I, II, or III+ in accordance with the Clavien–Dindo Classification[17]. Health economy indicators encompassed total length of stay (LOS), postoperative LOS, total hospitalization expense, and out-of-pocket expense.

2.3 Covariates

The following covariates were collected: demographics (age, gender and year of operation), tumor localization (left, right, bilateral, and retroperitoneal, etc.), biochemistry indicators (urine and blood cortisol, aldosterone, renin, aldosterone–renin ratio, normetanephrine, metanephrine, and 3-methoxytyramine), preoperative cardiopulmonary function (blood pressure, pulmonary function, cardiac risk [Goldman score], and electrocorticography), perioperative variables (tumor size, surgical method including laparoscopic, robotic, and open/conversion open, operative route including transabdominal and retro-peritoneal, as well as surgical time).

2.4 Statistical analysis

Means (standard deviation [SD]) or median (interquartile range[IQR]) were used to summarize the descriptive statistics for continuous variables where normally or non-normally distributed applicable while number and percentage were utilized for categorical data. Kruskal–Wallis test was applied to examine the overall statistical difference of continuous variables among groups, and a post hoc analysis between groups was further performed using the least significance difference approach. χ² test or Fisher exact test was utilized to assess statistical difference of categorical data among groups. Cochran–Armitage test was utilized to assess the trend of outcomes across years. All analyses were conducted with R software (version 4.3.1, R Foundation for Statistical Computing).

3 RESULTS

Among the 254 participants who underwent adrenalectomy for adrenal tumor over a 10-year period, the median age was 49 years (range: 6–81 years). Females accounted for 50.8% of the patients. Laparoscopic adrenalectomy was the most commonly performed surgical approach, representing 90.2% (n = 229) of the cases, while robotic (n = 12) and open surgery (n = 13) accounted for 4.7% and 5.1%, respectively. Additionally, a significant proportion of the patients' costs (78.7%) were covered by national health insurance in China, providing financial support for their medical expenses.

Characteristics of the disease functional diagnosis, locations, as well as pathological diagnosis are shown in Supporting Information, Figure S1. Among all the cases, 29.1% (n = 74), 29.1% (n = 74), 17.3% (n = 44), 15.7% (n = 40), and 8.6% (n = 22) were non-functioning tumors, primary aldosteronism (adenoma), other functional types, Cushing's syndrome, and pheochromocytoma, respectively, based on the functional diagnosis (Figure S1A). Over 90% of the tumors were unilateral, while 4.3% (n = 11) were bilateral and 2.0% (n = 5) were ectopic tumors (e.g., retroperitoneal, Figure S1B). Final pathological diagnoses were mostly concordant with the functional diagnosis (concordance rate: 96%). For example, a total of 57.1% (n = 145) were diagnosed as cortical adenoma (non-functioning tumor and primary aldosteronism), and 8.3% (n = 21) were diagnosed as pheochromocytoma (Figure S1C).

The majority surgical approach was laparoscopic operation (75%–100% across the years, Figure 1A and B). Open surgery was also an optional approach before 2019 (about 24%); however, it was no longer applied after the introduction of robotic system in 2021 in the institute. The robotic-assisted adrenalectomy accounted for 25.0% of the cases in 2023, and all the tumors larger than 5 cm in diameter were resected using this approach. About 19% of the pheochromocytoma cases were operated using robotic system (Figure 1C). This proportion raised to 75% in 2022 and 2023. This suggested that surgeons preferred robotic-assisted adrenalectomy for those patients given the more accurate and flexible instruments compared to open and laparoscopic approaches. As expected, significantly shorter operation time and less intraoperative blood loss were observed in laparoscopic and robotic-assisted approaches comparing to opening approaches (All p < 0.05, Table 1). We then evaluated postoperation complication rates. Twenty percent of the patients undergoing open surgical approaches and 17% of the patients undergoing robotic-assisted approaches were observed having severe post-operational complications (Grade III or above), which was significantly higher than the proportion among the patients who received laparoscopic surgery (2%, both p < 0.001, Table 2). There are 229 pateints receiving laparoscopic adrenalectomy. However, the sum of laparoscopic in Table 2 is 226. That is because prognosis records of 3 patients are missing. The pathologic diagnosis of them are respectively hematoma, pheochromocytoma and adrenal cyst. Further analysis suggested that the patients receiving open or robotic-assisted surgery would have larger tumor size than patients receiving laparoscopic surgery (mean ± SD: robotic 6.49 ± 2.40 cm, open 7.75 ± 5.25 cm, laparoscopic 3.00 ± 1.68 cm, all p < 0.001). Detailed information of the complications is shown in Figure S2 and Table S1.

We then performed a preliminary analysis of the application of ERAS in adrenal operation. ERAS was applied in only 3% of the postoperative patients in 2013–2015; however, this proportion increased to 46% in 2022–2023 (p_trend < 0.001, Figure 2A). To date, 70% of the patients avoid postoperative drainage, more than 90% of the patients avoid postoperative antibiotics and opioid analgesia (the percentage raised across the years, both p_trend values < 0.001, Figure 2B), and more than 70% of the patients avoid intravenous fluid therapy after the surgery (increased from 16%, p_trend < 0.001, Figure 2B). Notably, ERAS was more likely to be applied in patients who received minimally invasive surgery (laparoscopic or robotic-assisted approach) than in patients with open surgery (Figure 2C, all p < 0.05).

A preliminary analysis of the cost-effectiveness of ERAS application was also performed (Figure 3, and Table 3). Briefly, the total expense increased from Chinese Yuan (CNY) 15 700 in 2013 to CNY 21 600 in 2023. The annual increase rate is 3.24%, which is slightly higher than the average annual inflation rate of about 2%. However, the out-of-pocket expense for the patients decreased from CNY 11 700 in 2013 to CNY 2700 in 2023 (Figure 3A). A significant reduction in postoperative inpatient stay was also observed with the increased proportion of the ERAS application (from 6 days to 2.5 days) (Figure 3B). Further analysis shows that the application of the ERAS reduces the total expense, out-of-pocket expense, total inpatient stay, as well as the postoperative inpatient stay (all p < 0.05, Table 3).

4 DISCUSSION

In the present study, we conducted a comprehensive analysis using 11 years of electronic medical records from a single center to investigate the surgical treatment for adrenal tumors. The main finding of the study suggests that implementing an ERAS approach could significantly reduce hospital stay and the medical expense. Specifically, the ERAS approach for adrenal tumors may include avoiding postoperative drainage, antibiotics, opioid analgesia, and intravenous fluid support (4N approach).

Common complications of adrenalectomy include wound infection or hematoma, pleural effusion, pneumonia, respiratory failure, peritonitis, intra-operative and post-operative hemorrhage, and so forth[18,19]. In our study, we observed similar complications, with infection and bleeding being the most common. Additionally, two patients experienced muscular calf vein thrombosis, and 18 patients had post-operative infections that required antibiotic therapy. Eight of the patients had grade III complication. Among them, three received critical care due to excessive bleeding (> 500 mL) during operation. Specifically, two patients were attributed to large size tumor (9.5 cm and 7 cm). The other one received Whipple simultaneously due to cholangiocarcinoma. There are also two patients who were admitted into the intensive care unit (ICU) for just one interim night after surgery.

ERAS in our study involved avoiding drainage, antibiotics, opioid analgesia, and intravenous fluid (4N). The ERAS approach was first introduced in colorectal surgery and had been shown to reduce hospital stay, medical costs, and complications[20–22]. ERAS had also demonstrated benefits in adrenalectomy[23,24]. It was reported that total/post-operative length of hospital stay after the implementation of ERAS will decrease from 14.19/5.43 to 11.27/3.31 days. The medical expenses also decreased significantly owing to ERAS, from CNY 7143 to CNY 5670. Simultaneously, surgery-related complications like infection, urinary retention and retroperitoneal effusion in ERAS are not significantly more common than traditional peri-operative management[25]. As for specific approaches of ERAS in adrenalectomy, there are overlap and disparities in diverse studies. He et al. employed early mobilization, no intravenous fluid, no routine use of antibiotics, early urinary and catheter and drainage tube removal[25]. Another recent study took more advanced fast-track and enhanced recovery protocol, including admission on the day of surgery, standardized multimodality anesthesia, no post-operative urinary catheter, post-operative oral analgesics, early post-operative mobilization, enteral feeding, and early discharge[16]. There are also some controversies on ERAS. With the introduction of more complicated/multi-factorial ERAS programs, the possibility of delayed implementation increased[26]. Moreover, some components in ERAS, like pre-operative carbohydrate loading and bowel preparation, are suspected to be less evidence-based[27]. Our findings were comparable with the reported studies. This indicates that ERAS is an effective way for patients with adrenal tumor.

In terms of health economics, laparoscopic adrenalectomy is associated with the lowest hospitalization cost. A significant decrease in out-of-pocket expenses for patients was also observed, which was strongly associated with the application of the ERAS. Previous studies have demonstrated ERAS will significantly reduce total cost (mean difference: CNY 8186.53)[28]. A cost-effectiveness analysis on urologic oncology surgery demonstrated that the total cost was significantly lower in the ERAS group (26 650 US dollars vs. 31 138 US dollars). It was mainly attributed to decreased ICU expense, decreased LOS (4 days), and lower treatment-related costs[29]. The results from the present study confirmed the cost-effectiveness of the ERAS in patients with adrenal tumors. These preliminary results may need further evaluation in a future perspective study.

There are limitations in our study, including its retrospective nature based on medical records. Additionally, operations by different medical instruments or medical practitioners may introduce biases.

5 CONCLUSION

The proportion of ERAS (4N protocol: no drainage, no antibiotics, no opioid analgesia, and no intravenous fluids) among adrenal patients has increased over the past decade. Despite the rise in total expenses, out-of-pocket expenses for patients have significantly decreased over time via the implementation of the ERAS approach.

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