This study proposes that the preoperative PNI is an independent predictive factor for PPCs in gynecological cancer surgery patients. The findings highlight the importance of the nutritional status in optimizing surgical outcomes for gynecological cancer patients.
PPCs are common following curative surgery for major organ cancers, PPCs are associated with early postoperative mortality, ICU admission, and prolonged hospital stays [24–27]. The prediction of PPCs can minimize medical costs and reduce morbidity and mortality [18]. The ARISCAT risk index is a generally utilized and recognized risk stratification tool [28]. After comparing the predicting ability between the PNI and ARISCAT risk index through ROC curve analysis, this study found that the PNI exhibited better performance. Furthermore, a low PNI was identified as an independent predictor of PPCs, but a high ARISCAT risk index (≥ 26) was not. This discriminative performance suggests potential clinical value in forthcoming applications.
The PNI was developed to evaluate the immune-nutritional status [20]. The association between a low PNI and adverse prognostic outcomes has been identified in a wide range of cancers, such as gastric cancer [29], colorectal cancer [30], and gynecological cancer [21]. Especially, in gynecological cancers, a low PNI is associated with unfavorable overall survival and progression-free survival [31–33]. In addition to the long-term outcomes, the occurrence of PPCs is associated with the preoperative PNI in patients undergoing radical cystectomy [23]. This is consistent with the findings of our study, which showed that as the preoperative PNI decreased, the odds ratio of PPCs tended to increase. Notably, the PNI can be easily calculated based on serum albumin levels and the lymphocyte count in a peripheral blood test, making it a cost-effective tool. Thus, risk stratification using the PNI would be valuable in a clinical setting [29].
Malnutrition affects the respiratory system by reducing respiratory muscle mass and strength [34], worsening respiratory muscle function, and decreasing respiratory drive [35]. Furthermore, malnutrition compromises host defense mechanisms against infections [36] and inhibits lymphocyte transformation [37]. Consequently, malnutrition can make patients vulnerable to PPCs. Patients with gynecological cancer are predisposed to the risk of malnutrition. Previous studies conducted in developed countries have reported that more than one in five patients with gynecological cancer present with malnutrition at diagnosis [5, 38]. Hence, addressing malnutrition preoperatively can improve the clinical course in patients with gynecologic cancer.
While the PNI is a proven prediction parameter for various outcomes, its optimal cut-off value remains relatively unclear. Although a cut-off value of 45 has been suggested in many previous studies [23, 39–43], our results propose a higher value. In this study, the cut-off value was calculated for PPCs, and the results may differ from those of previous studies regarding the long-term outcomes. To evaluate the PNI, the study examined all gynecologic cancers together. However, the progression rates also depend on the origin of the gynecological cancer, i.e., the immuno-nutritional conditions of the patients were variable [44]. This cut-off discrepancy poses a barrier to the widespread clinical applicability of the PNI. However, based on the finding that the risk of PPCs tended to decrease with higher PNI values, PNI-guided nutrition management might be beneficial, and further study is required to verify this. Furthermore, since the PNI cut-off value remains inconclusive, further studies are needed to determine its optimal value.
The study investigated PPC risk factors in patients undergoing gynecological cancer surgery. In the IPTW-adjusted cohort, the independent risk factors were ovarian cancer, old age, lung disease, hypertension, preoperative white blood cell count, preoperative platelet count, crystalloid infused volume, operation duration, and laparotomy, and a favor factor was intraoperative red blood cell transfusion. Aging is a well-established risk factor for PPCs [45–48]. Declining swallowing and respiratory function, as well as the prevalence of sarcopenia, make the elderly vulnerable to PPCs [34]. The duration of surgery, underlying lung diseases, and infused fluid volume are also well-known risk factors of PPCs [17, 24, 49–51]. PPCs frequently occur in patients with ovarian cancer due to its rapid progression and wide surgical cover area. Studies have shown that the incidence of PPCs in ovarian cancer patients undergoing cytoreductive surgery ranged from 26.9–32.3% [52, 53]. Intraoperative diaphragmatic evaluation is required for patients undergoing cytoreductive surgery for advanced ovarian cancer [54, 55]. Diaphragmatic surgery is associated with a high risk of developing postoperative pleural effusion [56, 57]. In the IPTW analysis, primary cancer sites were initially matched, yet a robust association between ovarian cancer and PPCs was identified. Consequently, a subgroup analysis was conducted in patients with ovarian cancer, and the preoperative PNI was an independent predictive factor.
The low odds ratio of PPCs regarding intraoperative red blood cell transfusion contradicts findings from previous studies [58, 59]. Although no significant variable was identified in the co-linearity test and all matching variables were balanced, confounding variables might be masked. Another plausible explanation is focused management. Intraoperative blood transfusions are usually performed when there is a large amount of blood loss and insufficient circulating blood volume. In these situations, the human resources might be focused; the anesthetic management might be more attentive, and lung care might be more aggressive. Moreover, the surgery department might provide closer observation and management to patients transfused with blood products intraoperatively. However, due to the retrospective nature of the study, the criteria for transfusion, which was not investigated, were applied differently depending on the anesthesiologist in charge at the time. Therefore, a controlled study is needed to investigate the effects of transfusion.
This study has several limitations. First, although IPTW analysis was performed, unexpected selection bias may exist between the high and low PNI groups. Additionally, a cautious interpretation of the study results is advised since the data were collected from a single tertiary institution. Second, the focus on PPCs within 15 days after surgery limits insights into long-term respiratory effects. Long-term outcomes, including overall and progression-free survival, were regretfully not investigated in this study, despite their significant clinical relevance. Third, the study contributes to the literature but does not directly improve postoperative outcomes. Further prospective trials are needed to assess the impact of preoperative nutritional status on PPCs. Lastly, information regarding intraoperative pulmonary interventions, such as recruitment maneuvers and positive end-expiratory pressure, was not collected. Therefore, hidden effects from such interventions may exist that could not be determined during this study.
In conclusion, the preoperative PNI, reflecting both systemic inflammation and nutritional status, has the potential to predict PPCs in patients undergoing gynecological cancer surgery. The preoperative PNI can be a practical predictor, comparable to the ARISCAT risk index.