Perioperative management and outcomes of minimally invasive esophagectomy: case study of a high-volume tertiary center in Taiwan
Introduction
Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death (1). The mortality rate of esophagectomy remains high with associated procedural complexity. In addition, with different major histological types, mainly adenocarcinomas and squamous cell carcinomas, the postoperative complications and treatment may differ between Western and Asian countries (2). Recently there are significant progress in surgical techniques (3), intraoperative goaled-directed fluid management and perioperative care. Various forms of neoadjuvant concurrent chemoradiation therapy (CCRT) incorporating minimally invasive esophagectomy (MIE) procedures such as McKeown MIE and Ivor Lewis MIE have become the mainstay of surgical treatment for esophageal cancer. However, the perioperative management and short-term outcomes of these procedures have rarely been reported.
In the present study, we used 1-year patient data to analyze the type of surgical procedures, the postoperative complications, short-term outcomes, and postoperative management of patients with esophageal cancer who underwent esophagectomy and reconstruction at a high-volume medical center in Taiwan. The goals of this study are to compare the complications and the following treatment between different surgical procedures and to analyze if any preoperative coexisting disease and anesthesia conduct might be associated with postoperative complications and hospitalization course.
Methods
We retrospectively reviewed data from patients with esophageal cancer who had undergone surgical esophagectomy between January and December 2015. The surgical procedures were performed by either of the two chest surgeons in our center. Patient demographics, disease status, cancer staging, neoadjuvant CCRT, perioperative management, operative technique, and postoperative course were reviewed and extracted from electronic medical records and hand-written anesthetic sheets. The major postoperative complications and morbidities were recorded and categorized as follows: dysrhythmias, reintubations, acute kidney injury (AKI, defined as an increase in serum creatinine level by ≥0.3 mg/dL within 48 hours), pulmonary complications (including pneumonia, empyema, or pleural effusion requiring intervention), gastric(G)-tube complications (including anastomosis leakage, stenosis, or necrosis), chyle leakage, vocal cord paralysis (identified through bronchoscopic examination), iatrogenic hypoparathyroidism, and reoperations. In addition, 30- and 90-day mortality rates were recorded. The two mostly performed procedures, McKeown MIE and Ivor Lewis MIE were isolated for comparison. We also analyzed if major postoperative complications including dysrhythmias, lung complication, AKI, secondary surgical intervention, and 30-day mortality were associated with preexisting comorbidities. Statistical analysis was performed using Student’s t-test for continuous variables, and the association among the variables and the length of stay was tested using the Kruskal-Wallis test. The chi-squared test was used for categorical variables. In all analyses, P<0.05 was considered statistically significant. SPSS version 22.0 (International Business Machines, Armonk, NY, USA) was used for all analyses.
Results
In total, 64 patients received esophagectomy and reconstruction in 2015 in our hospital. Baseline demographic characteristics are listed in Table 1. Perioperative management and surgical procedures are listed in Table 2. Anesthesia conduct includes general anesthesia with 8.0 French endotracheal tube or pre-existing tracheostomy, invasive blood pressure monitoring, and central venous catheter placement. One lung ventilation during thoracoscopic stage of MIE was achieved using Coopdech endobronchial blocker tube and patients were positioned into left lateral decubitus position for all of our patients.
Full table
Full table
Overall, the mean intensive care unit (ICU) stay was 9.6±20.1 days and mean hospital stay was 28.4±25 days. Infusion of 6% hydroxyethyl starch (Voluven, Fresenius/Hospira, Germany), albumin, or blood during the intraoperative period was not associated with the length of ICU or hospital stay. However, postoperative arrhythmia and pulmonary complications were associated with a prolonged ICU stay (P=0.042 and 0.009, respectively) but not hospital stay (P=0.448 and 0.125, respectively). However, the occurrence of postoperative AKI was associated with both prolonged ICU stay (P=0.015) and hospital stay (P=0.017).
The most common postoperative complications included lung complications (18.7%), dysrhythmias (14.1%), anastomosis leakage (14.1%), vocal cord paralysis (9.4%), G-tube stenosis (4.7%), chyle leakage (4.7%), and AKI (4.7%). In our study, 25% of patients received secondary surgical interventions for the aforementioned complications. The 30- and 90-day mortality rates were 3.1% and 4.7% respectively.
The two most common surgical approaches, namely McKeown MIE and Ivor-Lewis MIE, were analyzed separately (Table 3). McKeown MIE required a significantly longer surgical time and significantly higher total volume of infused intraoperative crystalloid than did Ivor-Lewis MIE. The postoperative complications and patient outcomes of these two approaches are listed in Table 4. Neither major organ complications nor G-tube complications differed significantly between the two groups. However, there is a trend toward higher incidence of vocal cord paralysis McKeown MIE group (P=0.067) and chyle leakage in the Ivor-Lewis MIE group (P=0.064). In the McKeown MIE group, 30-day mortality was observed in one patient. However, 30-day mortality was not observed in the Ivor Lewis MIE group.
Full table
Full table
The association between major post-operative complications and pre-operative comorbidity are shown in Table 5. Patients with preoperative arrhythmias have a higher risk of developing post-operative dysrhythmia (P=0.013) and lung complications (P=0.036). Patients with underlying heart diseases are at higher risk of post-operative AKI (P=0.002) and second surgical intervention (P=0.013). Chronic kidney diseases are associated with post-operative dysrhythmia (P=0.013), lung complications (P=0.036) and post-operative AKI (P≤0.01).
Full table
Discussion
A total of 64 patients underwent surgical esophagectomy in our center in 2015, and the mortality rate was low (<5%). Hence, our results were consistent with those of previous studies in high-volume hospitals (4,5). According to previous investigations, procedural volume is a crucial determinant of the outcome of esophagectomy (6-8). Procedures performed in high-volume centers theoretically have favorable short-term outcomes and low mortality (4). However, hospital stays were longer as the majority of our patients were diagnosed of squamous cell carcinoma and consequently required additional operations on the upper esophagus. With optimal pulmonary protection and fluid management, 64.1% of our patients were extubated in the operation room.
However, pulmonary complications including empyema and pleural effusion remain the most common postoperative complications associated with prolonged ICU stay and the most common indications for further surgical intervention (6.4%). Yet hospital stays were not significantly prolonged by postoperative pulmonary complications. Our results differ from those of previous studies, which have suggested that isolated pulmonary complications are associated with prolonged hospital stays (9).
ICU stays are longer in our center when comparing to previous reports. In our center, all of the patients were transferred to ICU directly after esophagectomy, and 69% of the patients were transferred to general ward within 5 days. However, there are six patients stayed in ICU for more than four weeks, with the longest ICU stay being 125 days to be exact. These patients were all complicated with either anastomosis leakage, empyema, G-tube necrosis, or massive bleeding, and five of them received more than two reoperations. The other patient who had a prolonged ICU course is the oldest man in our cohort who is 81 years old and suffered from a delayed weaning process, leading to his prolonged ICU stay. To some extent, the relative longer ICU and hospital stay in our study can be explained by the whole-coverage national health insurance in Taiwan.
Previous studies have demonstrated that comorbidity influences outcomes with operative time, cardiovascular complications, anastomotic leakage, and overall survival in patients undergoing esophagectomy (5). In our study, preexisting heart disease, arrhythmia, and CKD are associated with major postoperative complications, whilst ASA classification, preexisting lung disease, presence of a second primary malignancy, and old cerebrovascular accident (CVA) play nonsignificant roles in postoperative complications. Charlson et al. had developed a weighed index of comorbidity for mortality, in which moderate to severe renal disease was assigned a weight of 2, whereas myocardial infarct, congestive heart failure, CVA, chronic pulmonary disease were assigned a weight of 1, indicating that chronic kidney disease itself does play a crucial role in morbidity and mortality (10). In our study, CKD is associated with more post-operative dysrhythmias, lung complications, and acute kidney injuries.
Our results suggest that with adequate monitoring and anesthetic management, operation time and infused volume did not affect postoperative outcomes. Although a longer operative duration and higher volume of infused crystalloids were observed with the McKeown MIE than the Ivor Lewis MIE, the postoperative complications and outcomes of both methods were comparable. Goal-directed fluid management guided by pulse pressure variation, stroke volume, or stroke volume variation are routinely used in our center; such management is advantageous for lengthy surgical procedures. However, complications differ with different surgical techniques. More patients were observed to have vocal cord paralysis in the McKeown MIE group; and a higher number of patients with chyle leakage were observed in the Ivor Lewis MIE group. Our results were similar to another retrospective report, in which a significantly higher incidence of vocal cord paralysis was associated with the McKeown MIE (11). For transthoracic esophagectomy, chylothorax is a well-known complication associated with high morbidity and mortality (12). A randomized controlled trial and a meta-analysis have reported that transthoracic esophagectomy is associated with a high incidence of pulmonary complications and chyle leakage and longer hospital stays (13,14).
In Western countries, distal esophageal and gastroesophageal adenocarcinomas account for >70% of upper gastrointestinal malignancies; however, squamous cell carcinomas were the most common type of esophageal malignancy in this study, reflecting the overall prevalence in Asia, according to a previous report (15). Our results showed that 87.5% of our patients received neoadjuvant CCRT and 97% received MIE. In addition, more complex and higher-risk procedures such as combing otolaryngologist for total laryngectomy with Mckeown method, or Ileo-colon interposition for esophageal reconstruction were performed for rescue of advanced-stage patients in our center. In addition to surgeon performance and hospital volume, the outcomes of highly complex surgical procedures such as esophagectomy rely heavily on staff from other hospital units and services, including the anesthetic team, ICU caregivers, nurses, nutritionists, and physical therapists (16,17). Strategies to minimize morbidity and mortality should be advocated, from preoperative patient selection to the implementation of standardized perioperative and multidisciplinary care pathways (18).
Our study has some limitations, such as its retrospective design, relatively small sample size, and relatively short-term follow up. Our results might have been more conclusive if we had extended the research period or included a larger number of patients for analysis. Prospective studies must be designed and undertaken to obtain more solid evidences.
Conclusions
Postoperative dysrhythmias, pulmonary complications, and AKI were significantly associated with prolonged ICU stay. Strategies to prevent post-operative AKI should be implemented to reduce the length of hospital stay. Comparable postoperative complications were observed in patients who underwent McKeown MIE and Ivor Lewis MIE despite differences in operative duration, intraoperatively administered fluids, including crystalloids, albumin, and Voluven; and administered blood products. The 30- and 90-day mortality rates in our study were low and were comparable to those reported in previous studies. Our results suggest that patients with preoperative comorbidity of arrhythmia, heart diseases, and CKD are associated with more common post-operative complications and more often require second surgical intervention.
Acknowledgements
Funding: This work was supported by the Ministry of Science and Technology, Taiwan, R.O.C. under Grant no. 105-2314-B-002 -019.
Footnote
Conflicts of Interest: The authors have no conflicts of interest to declare
Ethical Statement: The study was approved by the National Taiwan University Hospital Institutional Review Board (Protocol ID: 201708054RINB).
References
- Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359-86. [Crossref] [PubMed]
- Lu CL, Lang HC, Luo JC, et al. Increasing trend of the incidence of esophageal squamous cell carcinoma, but not adenocarcinoma, in Taiwan. Cancer Causes Control 2010;21:269-74. [Crossref] [PubMed]
- Jamieson GG, Mathew G, Ludemann R, et al. Postoperative mortality following oesophagectomy and problems in reporting its rate. Br J Surg 2004;91:943-7. [Crossref] [PubMed]
- Nhs E. Improving outcomes in upper gastrointestinal cancers—the manual. Guidance on commissioning cancer services. Available online: http://www.wales.nhs.uk/sites3/documents/362/UpperGIGuidance.pdf
- Dolan JP, Kaur T, Diggs BS, et al. Impact of comorbidity on outcomes and overall survival after open and minimally invasive esophagectomy for locally advanced esophageal cancer. Surg Endosc 2013;27:4094-103. [Crossref] [PubMed]
- Dikken JL, Dassen AE, Lemmens VE, et al. Effect of hospital volume on postoperative mortality and survival after oesophageal and gastric cancer surgery in the Netherlands between 1989 and 2009. Eur J Cancer 2012;48:1004-13. [Crossref] [PubMed]
- Wouters MW, Gooiker GA, van Sandick JW, et al. The volume-outcome relation in the surgical treatment of esophageal cancer: a systematic review and meta-analysis. Cancer 2012;118:1754-63. [Crossref] [PubMed]
- Markar SR, Karthikesalingam A, Thrumurthy S, et al. Volume-outcome relationship in surgery for esophageal malignancy: systematic review and meta-analysis 2000-2011. J Gastrointest Surg 2012;16:1055-63. [Crossref] [PubMed]
- Straatman J, van der Wielen N, Nieuwenhuijzen GAP, et al. Techniques and short-term outcomes for total minimally invasive Ivor Lewis esophageal resection in distal esophageal and gastroesophageal junction cancers: pooled data from six European centers. Surgical Endoscopy 2017;31:119-26. [Crossref] [PubMed]
- Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83. [Crossref] [PubMed]
- Luketich JD, Pennathur A, Awais O, et al. Outcomes after minimally invasive esophagectomy: review of over 1000 patients. Ann Surg 2012;256:95-103. [Crossref] [PubMed]
- Brinkmann S, Schroeder W, Junggeburth K, et al. Incidence and management of chylothorax after Ivor Lewis esophagectomy for cancer of the esophagus. J Thorac Cardiovasc Surg 2016;151:1398-404. [Crossref] [PubMed]
- Hulscher JBF, van Sandick JW, de Boer AGEM, et al. Extended Transthoracic Resection Compared with Limited Transhiatal Resection for Adenocarcinoma of the Esophagus. N Engl J Med 2002;347:1662-9. [Crossref] [PubMed]
- Hulscher JB, Tijssen JG, Obertop H, et al. Transthoracic versus transhiatal resection for carcinoma of the esophagus: a meta-analysis. Ann Thorac Surg 2001;72:306-13. [Crossref] [PubMed]
- Ahmed ME, Mahadi SI, Ali BM. The surgical treatment of esophageal cancer in Sudan: A 100 consecutive cases. Int J Surg 2016;29:101-7. [Crossref] [PubMed]
- Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med 2009;361:1368-75. [Crossref] [PubMed]
- Louie BE. Is esophagectomy the paradigm for volume-outcome relationships? J Gastrointest Surg 2010;14 Suppl 1:S115-20. [Crossref] [PubMed]
- Markar SR, Schmidt H, Kunz S, et al. Evolution of standardized clinical pathways: refining multidisciplinary care and process to improve outcomes of the surgical treatment of esophageal cancer. J Gastrointest Surg 2014;18:1238-46. [Crossref] [PubMed]