Our current study revealed complications after esophageal cancer surgery, especially pulmonary complications, to exert long-term negative impacts on HRQoL outcomes and nutritional status. Pulmonary complications were associated with increases in problems related to reflux/coughing and eating, while not worsening pain-related symptoms. Notably, patients with pulmonary complications had long-lasting poor nutritional status.
Esophagectomy is still associated with considerable morbidity; the overall incidence of complications is reportedly approximately 60% [13]. These complications must be managed very carefully to prevent early postoperative mortality [16, 24]. Importantly, with an increasing number of long-term survivors after curative resection for EC, the long-term impacts of postoperative complications have recently been highlighted [29]. The influences of postoperative complications on survival outcomes [14, 15, 24] and HRQoL outcomes [10–12] have, in fact, been investigated.
Generally, the HRQoL of patients undergoing esophagectomy markedly deteriorates immediately after surgery, but then gradually recovers to a nearly preoperative level within 3 to 5 years after surgery [30]; however, some patients do not experience restored HRQoL after surgery [3], experiencing multiple concurrent long-persisting symptoms, such as reflux and eating problems [31]. Recently, minimally invasive surgical approaches have reportedly yielded good postoperative HRQoL outcomes [5, 32], due mainly to reducing pain-related symptoms [6, 33]. Our recent findings suggested robot-assisted transmediastinal esophagectomy to reduce reflux problems [5], but an abundance of evidence has shown that symptoms associated with eating, reflux and coughing are refractory and difficult to ameliorate with surgical modifications [6]. Rather, postoperative complications reportedly exert long-lasting negative effects on HRQoL outcomes including eating problems [10–12].
In our study, overall complications had modest impacts on HRQoL outcomes. Therefore, in order to further dissect the effects of each individual complication, we focused on two major complications and investigated their individual impacts. Notably, the impacts of pulmonary complications on HRQoL and nutritional status differed from those of anastomotic leakage. Patients with anastomotic leakage had more pain, speaking and dysphagia problems at 6 months after surgery, although these negative effects had diminished at 2 years postoperatively, a finding in agreement with those of previous studies [12, 17].
Most importantly, pulmonary complications exerted negative impacts on several aspects of HRQoL over time. Most notably, pulmonary complications were associated with more dry mouth, coughing and reflux, all of which correlate highly with each other [34], at a later time after esophagectomy. These symptoms reportedly cause insomnia [29], which might explain the observation that patients with pulmonary complications had significantly worse insomnia at 2 years after surgery than those without such complications. Furthermore, patients with pulmonary complications had more symptoms of nausea/vomiting and eating difficulties than those without these complications at 2 years after surgery, although the differences were not statistically significant (P = 0.051 and 0.06, respectively).
The presence of pulmonary complications was significantly associated with poor nutritional status. These observations raise the possibility that pulmonary complications led to an increase in reflux, coughing and eating difficulties, resulting in malnutrition [35]. On the other hand, previous studies have suggested that eating problems contributed to postoperative malnutrition, whereas dysphagia and reflux did not [36]. Although nutritional status appears to be a good indicator when estimating HRQoL, the relationship between each HRQoL measure and nutritional status has yet to be fully addressed [37]. We also evaluated body composition data, but detected no significant differences according to whether or not postoperative complications developed.
Poor HRQoL at 6 months after esophageal cancer surgery is reportedly associated with increased mortality risk [38]. Patients with postoperative complications, especially pulmonary complications, reportedly had poor survival outcomes [14, 15]. Notably, the negative survival impact of pulmonary complications is not due to an increase in cancer-related death, but rather mainly to more non-cancer deaths [14, 24]. Our observations, together with those of a recent study [15], indicate that pulmonary complications potentially worsen a patient’s general medical conditions, resulting in increased all-cause mortality.
The proven impacts of postoperative complications allow clinicians to optimize perioperative strategies in order to minimize complications. Surgical complications can reportedly be reduced by improving surgeon volume and experience [39]. Pulmonary complications can be prevented by smoking cessation before surgery, perioperative pulmonary rehabilitation and minimally invasive surgery [40, 41]. The benefit of extended nutritional support in patients undergoing esophagectomy remains controversial [42], but intensive nutritional interventions might benefit patients with postoperative complications given that such aggressive interventions are known to be beneficial, especially for severely malnourished patients [43].
Our study has limitations. First, it was a single-institution study. It seems likely that a multi-center collaborative study with a large cohort could achieve more convincing results. On the other hand, all of our patients underwent the standardized surgical procedure with high lymph node yield at an experienced center with a high volume of patients [44]; our findings are thus reliable. Second, the small patient number has limited statistical power. Additionally, the sample size of long-term survivors was further limited due to the poor long-term outcomes of EC patients. Third, we did not evaluate the association between the severity of the complications and HRQoL outcomes, which merits further detailed examination in future studies. Lastly, we evaluated the impacts of pulmonary complications and anastomotic leakage separately, but some patients had both of these complications since medical complications often lead to surgical complications and vice versa. This potential mixed cause-effect pattern must be taken into consideration when interpreting the results.
In conclusion, our findings suggest postoperative complications, especially pulmonary complications, to have a negative effect on HRQoL outcomes, leading to poor nutritional status over the long term after esophagectomy. Our results are anticipated to help clinicians take measures to prevent complications and optimize postoperative long-term strategies, thereby improving the HRQoL of patients.