Using the preoperative prognostic nutritional index as a predictive factor for non-cancer-related death in post-curative resection gastric cancer patients: a retrospective cohort study

We conducted a retrospective cohort study where we reviewed the medical records of 222 GC patients who underwent gastrectomy between May 2011 and April 2014 at Onomichi General Hospital, Hiroshima, Japan. Thirty-two patients with Stage IV were ineligible. All patients were histologically confirmed to have stage I, II, or III gastric adenocarcinomas via the Japanese classification of gastric carcinoma: 3rd English edition [8]. From these patients we selected who had R0 operation; 3 patients with microscopically incomplete resection (R1) or 5 patients with macroscopically incomplete resection (R2) were excluded. The study profile is shown in Fig. 1.

Almost all patients underwent total or distal gastrectomy and D1+ or D2 lymph node dissection in accordance with the Japanese Gastric Cancer Treatment Guidelines published in 2010 (ver. 3) [9]. The patients’ medical records were reviewed to gather data, including age, gender, body mass index, comorbidities, preoperative laboratory test results (absolute neutrophil and lymphocyte counts, and serum albumin and C-reactive protein (CRP) concentrations), surgical procedures, surgical pathology reports, and survival times.

In accordance with current clinical guidelines, postoperative patients with stage II and III GC and no marked comorbidities that would preclude chemotherapy use, were offered 5-fluorouracil-based adjuvant chemotherapy [10] after discussing with the patients and their family members. Postoperative follow-ups, which included physical examinations, laboratory tests, chest and abdominal cavity enhanced computed tomography, and upper gastrointestinal endoscopy, were conducted within 5 years post-operation, or until death, in accordance with the Japanese Gastric Cancer Treatment Guidelines [9]. The latest follow-up was on March 2017, and the median follow-up period was 39 months (range, 1–72). Overall survival (OS) was defined as the time between the date of surgery and death or the last available follow-up, and recurrence-free survival (RFS) was defined as the time between the date of surgery and disease recurrence or the last available follow-up.

The Clavien-Dindo classification system was applied in grading the postoperative complications [11]. These grades are as follows: grade 1 (any deviation from the normal postoperative course without the need for pharmacologic treatment or surgical, endoscopic, or radiologic interventions), grade 2 (pharmacologic treatment required), grade 3 (surgical, endoscopic, or radiologic intervention required), grade 4 (life-threatening complications requiring intensive care unit (ICU) management), and grade 5 (patient death). Complications classified as grade 3 or higher were considered major.

Routine blood and biochemical tests were conducted on the day before surgery to obtain patients’ absolute neutrophil and lymphocyte counts, and serum albumin and CRP concentrations. Patients’ mGPS was evaluated, and patients with high CRP levels (> 0.5 mg/dL) and hypoalbuminemia (< 3.5 g/dL) were given an mGPS of 2. Patients exhibiting only one of these parameters were given an mGPS of 1. Patients exhibiting neither of these parameters were given an mGPS of 0 [12]. After NLRs were calculated, we defined a low NLR as an NLR <  2.5 and a high NLR as an NLR ≥ 2.5 [13]. Patients were divided into either the low or high NLR group. The PNI score was calculated using the following formula: 10 × serum albumin concentration (g/dL) + 0.005 × lymphocyte count (number/mm²), as proposed by Onodera et al. [14] Generally, the resection and anastomosis of gastrointestinal tracts can be performed safely on patients with a PNI score of over 45, but these procedures may be dangerous for patients with a PNI score between 40 and 45. Additionally, these procedures may be contraindicated for patients with a PNI score of less than 40. Therefore, we defined a low PNI score as a score <  45 and a high PNI score as a score ≥ 45 [15]. Patients were also divided into either the low or high PNI group.

Tumor markers, including serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19–9), were examined preoperatively. The cut-off points for normal serum levels were 5.5 U/dL for CEA and 37 U/dL for CA19–9.

A simple univariate logistic regression analysis was used to evaluate the association between PNI score and other clinicopathologic factors. The Kaplan-Meier method was used to estimate cumulative survival and assess the relationship between survival and prognostic factors (Fig. 2), and the statistical significance of differences was assessed via the log-rank test. The multivariable Cox proportional hazard model was applied for variables that proved to be significant in a univariate analysis. These statistical analyses were performed using SPSS Statistics software (version 19; SPSS, Chicago, IL, USA). A P-value of < 0.05 was considered statistically significant. In addition, to assess the statistical significance of PNI as a prognostic factor for non-GC-related death, a cumulative incidence analysis was performed using Gray’s test. GC-related deaths were considered to be competing risk events because GC-related deaths prevented the occurrence of non-GC-related deaths. By calculating the cumulative incidence function, death was taken in to account as a competing risk factor. Cumulative incidence function was plotted for, both, the whole cohort and the subgroups stratified by pStage. The Fine and Gray model was used to measure the burden of cumulative incidence of non-GC-related death and strength of its association with potential prognostic factors. All variables were used to select the model using a stepwise method with Bayesian information criterion. These statistical analyses were performed using R software (version 3.25).