The number of elderly patients with hepatocellular carcinoma (HCC) has been increasing, but it remains unclear whether hepatectomy can be performed using the same criteria as in younger patients. Furthermore, the appropriate preoperative evaluation for hepatectomy in elderly patients is not yet clearly defined. Here, we investigated the applicability of preoperative assessment using the Controlling Nutritional Status (CONUT) score to help improve hepatectomy outcomes in elderly patients with HCC. This was a single-center retrospective analysis, and the study population comprised 64 consecutive patients who underwent hepatectomy for HCC between January 2012 and August 2016. We compared the preoperative assessment and perioperative outcomes between elderly (≥ 75 years old) and younger (< 75 years old)
patients. A total of 61 patients were reviewed. Poor preoperative CONUT score was associated with a longer postoperative hospital stay in elderly patients undergoing hepatectomy for HCC. In addition, although elderly patients had similar perioperative outcomes to younger patients, the incidence of delirium was significantly higher, and univariate analysis confirmed that old age is a risk factor for delirium among the preoperative factors. Hepatectomy for HCC in the elderly can be safely performed with appropriate preoperative nutritional assessment using CONUT score and prevention of postoperative delirium.
Preoperative nutritional assessment using the CONUT score was useful in predicting prolonged hospitalization for elderly hepatectomy with HCC.
Introduction
The aging of the global population is continuously progressing, and appropriate cancer treatment for the elderly is becoming increasingly important. Primary liver cancer was the sixth most commonly diagnosed cancer and the third leading cause of death from cancer in 2020 worldwide, approximately 80% of which were hepatocellular carcinoma (HCC) (Sung et al. 2021). The number of elderly patients with HCC is expected to further increase in the future. Percutaneous therapies, such as microwave coagulation and radiofrequency ablation (RFA) for HCC in the elderly, are minimally invasive and can be easily performed compared to surgery (Yamazaki et al. 2014). In contrast, hepatectomy in the elderly is considered high-risk because of the high incidence of postoperative complications (Zhou et al. 2013). However, due to the development of advanced surgical techniques such as laparoscopic hepatectomy (LH) and better perioperative management using the enhanced recovery after surgery (ERAS) protocol, hepatectomy has been increasingly performed in the elderly (Kaibori et al.
2019a). The elderly is generally known to undergo agerelated declines in cardiopulmonary function and metabolism, as well as develop multiple underlying medical comorbidities. In addition, it is said that the elderly is more likely to develop consciousness disorder accompanied by psychiatric symptoms, so-called postoperative delirium (POD), due to the upset physical condition after surgery.
Symptoms of POD include various problematic behaviors, such as removal of catheters and intravenous lines by the patient, difficulty in maintaining rest, and disturbed sleepwake cycle, resulting in longer hospital stays, additional nursing care, and greater medical costs (Park et al. 2017).
Therefore, it is unclear whether they can be operated on using the same criteria as those applied in younger patients. The preoperative nutritional status of the elderly has a significant impact on postoperative recovery (Borloni et al. 2019). Nutritional status varies greatly in patients, and careful assessment of preoperative nutritional status is essential. The Controlling Nutritional Status (CONUT) score has been developed as a nutritional screening tool calculated using measurements of serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration (Ignacio de Ulibarri et al. 2005). In this scoring system, the level of malnutrition is classified into four levels: normal, mild, moderate, and severe; the higher the score, the more severe the malnutrition is. Due to the accessibility of obtaining these laboratory parameters, the CONUT score is convenient and easy to use for determining the nutritional status of patients. Recently, the CONUT score has been reported to be associated with postoperative complications, hepatic functional reserve, overall survival (OS), and recurrence free survival (RFS) following hepatectomy (Harimoto et al. 2017, 2018; Takagi et al. 2017, 2019a, b); however, there have been few reports using CONUT with a focus on liver resection in the elderly.
Therefore, we investigated whether hepatectomy for HCC can be performed safely in elderly patients compared with
younger patients, and how preoperative assessment of nutritional status using the CONUT score affects the short-term
and long-term outcomes of hepatectomy in elderly patients.
Methods
Ethical considerations
The present study was approved by the Institutional Review Board of Iwate Prefectural Central Hospital (No. 617) and performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Furthermore, the need for informed consent was waived because of the retrospective nature of the study. We reviewed 64 consecutive patients who underwent hepatectomy, excluding 55 patients who underwent RFA, out of 119 HCC patients at Iwate Prefectural Central Hospital between January 2012 and April 2016.
Subjects
Elderly patients were defined as those aged 75 years and above, and younger patients were defined as those aged less than 75 years; according to these, patients were classified into elderly and younger groups. The diagnosis of HCC was confirmed by histological examination after hepatectomy. Patient characteristics and perioperative data were extracted from clinical records and laboratory reports. In addition, the length of postoperative hospital stay and the 1- and 2-year OS and RFS were examined. The preoperative condition was evaluated using the American Society of Anesthesiologists (ASA) physical status classification system (Mak et al. 2002). The indications for hepatectomy were evaluated according to the extent of the tumor progression, liver function, and general condition of the patients. As long as the patient is in good general condition and can walk, there were no restrictions on surgery based on age. In our hospital, patients with an ASA 4 or more were considered contraindicated for hepatectomy except for emergency surgery. For hepatectomy for HCC, anatomic resection was performed as indicated. For non-anatomic partial resection, LH was performed where possible. Major hepatectomy was defined as the resection of four or more liver segments, while minor hepatectomy was defined as the resection of less than four liver segments. Perioperative management of patients undergoing hepatectomy was based on the clinical pathway provided in the modified ERAS protocols in hepatectomy for HCC (Fujio et al. 2020). POD was diagnosed by intensive care unit (ICU) nurses using the Intensive Care Delirium Screening Checklist (ICDSC) (Bergeron et al. 2001), which is a widely used diagnostic algorithm for the identification of delirium and has been shown to have a high sensitivity and specificity. The
abdominal drain was withdrawn on postoperative day 2 or 3 if no bile leakage was observed. The criteria for discharge
were in accordance with our ERAS protocol (Fujio et al. 2020). The Clavien-Dindo classification was used to classify postoperative complications. Grade III or higher complications were considered severe.
Preoperative blood samples were obtained within 1 week before the hepatectomy. Preoperative CONUT score was calculated based on serum albumin concentration, total peripheral lymphocyte count, and total cholesterol concentration for nutritional assessment (Ignacio de Ulibarri et al. 2005). An investigation of the cut-off value for the CONUT score using the receiver operating characteristic (ROC) curve showed that the most appropriate cut-off value for the CONUT score was 3 (AUC = 0.621, P = 0.038, sensitivity = 0.804, specificity = 0.412). Therefore, we set 3 as the cut-off value for the CONUT score in this study and classified the patients into high and low CONUT groups.
Statistical analysis
Continuous data are expressed as the mean and standard deviation. The differences between the elderly and younger groups were analyzed using the Student’s t-test.
Fisher’s exact test or chi-square test was used for categorical variables. Univariate analysis was performed using a logistic regression model. The OS and RFS rates were estimated using the Kaplan-Meier method. All analyses were performed using the JMP® Pro 15 software program (SAS Institute Inc., Cary, NC, USA). Differences were considered statistically significant at P < 0.05.