This study yielded several interesting results on the association between preoperative malnutrition estimated using the CONUT scores and short-term outcomes after esophagectomy for esophageal cancer. First, moderate and severe malnutrition in CONUT was significantly associated with several disadvantageous patient characteristics, such as a low BMI, poor PS, poor ASA-PS, and frequent comorbidity. Second, it was also significantly associated with several disadvantageous cancer-related factors, such as advanced cancer stage and frequent preoperative treatment. Third, patients with moderate and severe malnutrition in CONUT who underwent OE had significantly more frequent postoperative severe, respiratory, and cardiovascular morbidities. Finally, malnutrition did not increase the incidence of postoperative morbidities after MIE.
Several studies have suggested that preoperative malnutrition could cause frequent post-esophagectomy morbidities [6, 13]. However, OE and MIE were not distinctly analyzed in these studies. Thus, the effect of MIE on the incidence of post-esophagectomy morbidities in patients with a poor nutritional status has not been well established. To the best of our knowledge, this is the first study to elucidate that preoperative malnutrition in CONUT was associated with worse short-term outcomes only after OE, but not after MIE.
CONUT was calculated using the serum albumin and total cholesterol levels and total lymphocyte count (TLC). Serum albumin levels reflect the nutritional status, inflammation, liver dysfunction, and kidney disease [14, 15]. Total cholesterol levels reflect the nutritional status related to lipid metabolism and inflammation [16, 17]. TLC is an indicator of nutrition and immunity [18]. Deterioration in these parameters can adversely affect tissue repair and resistance against infection, which may be a reason for the increased incidence of postoperative morbidities. Moreover, in this study, malnutrition estimated using the CONUT score was associated with disadvantageous patient characteristics and tumor-related factors for post-esophagectomy morbidity, which might result in frequent post-esophagectomy morbidity and surgery-related mortality [2]. These associations may explain why malnutrition estimated using the CONUT score could be a significant risk factor for postoperative morbidities after OE.
Nevertheless, malnutrition in CONUT did not affect the incidence of postoperative morbidities after MIE. Studies have reported that MIE is less invasive than OE is and is associated with fewer postoperative morbidities [19]. Several studies have suggested that the low invasiveness of MIE could alleviate the effect of preoperative disadvantageous clinical factors on the incidence of post-esophagectomy morbidities [3, 4]. High preoperative HbA1c levels can be a risk factor for anastomotic leakage, surgical site infection, and pneumonia after esophagectomy [20]. However, it might increase morbidities only after OE, but not after MIE [3]. Moreover, we have reported that a high pretreatment red blood cell distribution width, which is a surrogate marker of the nutritional status, might be an independent risk factor for severe morbidity and reoperation only after OE [4]. These previous studies may support the current result that malnutrition in CONUT could increase the incidence of morbidities only after OE, but not after MIE.
For patients assessed as being malnourished in CONUT, preoperative nutritional interventions may be effective in improving the short-term outcomes. A meta-analysis suggested that the administration of immunoenhancing enteral nutrition might reduce postoperative morbidities after gastrointestinal surgeries [21]. In contrast, a randomized controlled trial suggested that short-term nutritional intervention (7 days before esophagectomy) did not reduce post-esophagectomy morbidities. Thus, long-term nutritional intervention during preoperative treatment should be considered in malnourished patients scheduled to undergo esophagectomy [22]. Improvement in oral ingestion during preoperative treatment via stent insertion for patients with swallowing difficulty due to advanced esophageal cancer may also reduce post-esophagectomy mortality [23].
In this study, malnutrition in CONUT was an independent risk factor for respiratory morbidity after OE. Thus, when patients with malnutrition undergo OE, measures should be taken against respiratory morbidities. Smoking and impaired respiratory function could be risk factors for respiratory morbidities after esophagectomy [24, 25]. Thus, smoking cessation [25] and preoperative respiratory rehabilitation [26] are necessary. Moreover, oral hygiene [27], enforcement of the Enhanced Recovery after Surgery Program [28], and perioperative management by a multidisciplinary perioperative care team [29] are helpful in reducing post-esophagectomy respiratory morbidities. In addition, less invasive surgeries may further reduce post-esophagectomy morbidities in patients with malnutrition undergoing OE. A meta-analysis suggested that compared to MIE, robot-assisted esophagectomy may help reduce the incidence of pneumonia [30]. Transhiatal esophagectomy and mediastinoscopic esophagectomy are also effective candidates for further reducing postoperative respiratory morbidities [31, 32]. These procedures can be treatment options for patients assessed as being malnourished according to their CONUT scores.
This study had several limitations. Because this was a single-center retrospective study conducted over a long period, historical biases with regard to treatment strategy, surgery, and perioperative management existed. Notably, MIEs were more frequently performed in recent cases, and this strategy affected the current results, wherein malnutrition did not increase the incidence of morbidities after MIE. Moreover, the exclusion of patients owing to the lack of data could be a cause of a selection bias.
Nevertheless, our findings revealed that moderate and severe malnutrition assessed using the preoperative CONUT score can be a predictor of severe, respiratory, and cardiovascular morbidities after OE. Moreover, the low invasiveness of MIE might reduce the effect of preoperative malnutrition on worse short-term outcomes.