Onodera et al. first described the PNI in 1984 and calculated it by using the serum albumin concentration and total lymphocyte count from peripheral blood samples. It has been used as a nutritional and immunological indicator, and it was originally defined as a predictor of postoperative complications in patients with gastrointestinal cancers . Only the serum albumin value and lymphocyte count were correlated with the preoperative nutritional evaluation index and incidence of postoperative complications, which led to the use of the functional equation in stepwise discriminant analysis.
The PNI is easy to measure on a daily basis because it is inexpensive and very convenient compared to tumor markers. The PNI may also have a higher applicability for evaluating patients’ systemic inflammatory response. Therefore, it is a simple, reliable, inexpensive, and reproducible method whose interpretation is relatively easy in the context of non-septic neoplasia. Recently, the PNI has been widely using to evaluate preoperative prognostic factors for many malignant diseases . Some studies reported use of the PNI in patients with ESCC. However, there is controversy over the optimal cutoff point of the PNI to predict cancer survival. The cutoff value is normally set to 45 ; however, the optimal cutoff value of the PNI for predicting the long-term prognosis of ESCC remains unknown.
Tables 4a and 4b summarize recent studies about the relationship between the preoperative PNI and long-term outcome in patients with esophageal cancer. Table 4a shows studies with significant differences[16-18], and Table 4b shows studies with no significant differences[5, 7, 19-21]. A significant difference was not found between the cutoff values near 45 and 50, but a significant difference was often found for cutoff values from 46 to 49.
In recent studies of long-term results for other organ cancer, significant differences were seen for cutoff values close to or lower than 45; for example, in Hirahara et al. and Nozoe et al.’s studies, the cutoff values were 44.3 for gastric cancer  and 40 for colon cancer 40, respectively . Since esophageal cancer has a poor prognosis, a cutoff value slightly higher than 45 would be needed. In our study, the cutoff value derived by ROC curves was 46.8.
The mechanism of the independent correlation between the PNI and postoperative survival in patients with ESCC is unclear. Previous studies have suggested that albumin and lymphocyte levels are closely related to the presence of an inflammatory response in patients with cancer . There is a strong connection between inflammation and cancer . Therefore, it is logical that the PNI reflects systemic inflammation, considering its relationship with prognosis. It has been suggested that markers based on inflammation may reflect tumor burden and a positive treatment response. Inflammation promotes cancer cell proliferation, tumor angiogenesis, and metastasis. Systemic inflammation can increase the number of neutrophils and decrease the number of lymphocytes. Lymphocytes play a central role in antitumor immunity, and lymphocytopenia reflects impaired cellular immunity against cancer cells  . Furthermore, pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha, have been shown to lower serum albumin levels by reducing the production of serum albumin by hepatocytes . Thus, a low PNI is indicative of a tumor with greater malignant potential.
An accurate assessment of the postoperative risk of recurrence is important in planning customized risk-adaptive treatment strategies for each patient. In particular, identifying prognostic factors preoperatively is important for determining optimal preoperative treatment, and improving postoperative short-term and long-term outcomes . Previous studies have shown that perioperative immuno-nutritional support improves the nutritional and immunological statuses of patients undergoing elective surgery . However, it is still unclear whether such nutritional intervention will help improve the surgical outcome of patients with a low PNI. A larger randomized, multicenter, prospective study is needed to help clarify this.