Preoperative malnutrition and prognosis after neoadjuvant chemotherapy followed by subsequent esophagectomy
Editorial

Preoperative malnutrition and prognosis after neoadjuvant chemotherapy followed by subsequent esophagectomy

Naoya Yoshida, Yoshifumi Baba, Hideo Baba

Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

Correspondence to: Hideo Baba, MD, PhD, FACS. Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto 860-8556, Japan. Email: hdobaba@kumamoto-u.ac.jp.

Provenance: This is an invited Editorial commissioned by Section Editor Dr. Di Lu (Department of Thoracic Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China).

Comment on: Nakatani M, Migita K, Matsumoto S, et al. Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy. Dis Esophagus 2017;30:1-7.


Submitted Aug 09, 2017. Accepted for publication Aug 28, 2017.

doi: 10.21037/jtd.2017.09.02


Preoperative malnutrition has been reported to correlate with unfavorable long-term outcomes in patients who undergo surgery for gastroenterological cancers, including esophageal (1-4), gastric (5), colorectal (6), and pancreatic (7) cancers and hepatocellular carcinoma (8). Appropriate methods are needed to preoperatively assess malnutrition likely to adversely affect long-term outcome. Although blood test data, such as serum albumin, transthyretin, transferrin, and cholesterol concentrations and total lymphocyte count (TLC) are candidate markers of nutritional status, suitable comprehensive indicators to estimate long-term postoperative outcomes have not been identified. Prognostic nutritional index (PNI), calculated as 10 × albumin (g/dL) + 0.005 × TLC (/µL), was the first nutrition-related indicator of the risk of complications after gastrointestinal cancers surgery (9) and is a useful predictor of long-term outcome after surgery for various gastrointestinal cancers (3,4,7,8,10). Predictive markers of prognosis after esophagectomy in patients with esophageal cancer include preoperative sarcopenia (11), body mass index (12), controlling nutritional status (CONUT) (1,2) and PNI (3,4).

In the current study, Nakatani et al. retrospectively investigated 66 patients with squamous cell esophageal cancer who underwent neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil, followed by esophagectomy. All patients had resectable advanced esophageal cancer (stage II and III, not T4), and most (97%) completed two courses of NAC. Patients who underwent R1 or R2 resection and those who died in-hospital were excluded. The mean follow-up duration was 31.9 months. The study showed that preoperative PNI was significantly worse than pre-NAC PNI and that preoperative PNI (<45) was an independent unfavorable prognostic factor after NAC followed by esophagectomy, whereas pre-NAC PNI was not.

This study is clinically meaningful, because it is the first to demonstrate the usefulness of preoperative PNI as a prognostic indicator after NAC followed by esophagectomy. Current standard treatment for resectable advanced esophageal cancer consists of neoadjuvant therapy followed by surgery (13-15). Although, preoperative PNI was previously reported useful to predict prognosis after esophagectomy (3,4), those studies were not designed solely for patients who received NAC.

Although it is interesting to use PNI to preoperatively estimate unfavorable long-term outcomes, it is more important to determine whether preoperative nutritional intervention during NAC can improve both PNI and long-term outcomes after esophagectomy. Several studies have shown that preoperative nutritional intervention may reduce the incidence of postoperative morbidities (16,17). However, no studies to date showed that these nutritional interventions could improve long-term outcomes after esophagectomy. As indicated by Nakatani et al., maintaining or improving nutrition during NAC is important. In addition to conventional interventions, several novel approaches were suggested. Esophageal stenting in patients with stenosis during preoperative chemotherapy has been shown effective in maintaining preoperative nutrition (18,19). In addition, ghrelin administration may help maintain body weight and minimize the deterioration of nutritional status during chemotherapy (20).

It remains unclear whether PNI can serve as a nutritional or prognostic marker in patients who undergo esophagectomy for esophageal cancer. Albumin concentration and TLC may not accurately reflect nutritional status, as these parameters are affected by other factors, including systemic inflammation, liver function, changes in body fluid volume, and preoperative treatment, resulting albumin concentration and TLC having low sensitivity and specificity for assessing changes in nutritional status (21). Nutritional status can be reliably determined by nutritional risk screening (22) or by subjective global assessment in cancer patients (23), indices that focus on health history and physical examination and eliminate the ambiguity of non-specific, relatively insensitive laboratory values. Thus, although PNI may not be a reliable marker of malnutrition, it probably has prognostic value, as shown in this study.

The study by Nakatani et al. had several limitations. It was a retrospective study based on the medical records at a single institute. Sample size was small. Indications and methods of nutritional intervention during NAC were not fixed. In addition, the parameters used for univariate and multivariate analyses were unknown. Poor PNI may only reflect anorexia caused by cancer progression or organ dysfunction. Thus, interactions between PNI (<45 vs. ≥45) and other parameters should be examined.

In conclusion, to our knowledge, the current study is the first to demonstrate the usefulness of preoperative PNI (<45 vs. ≥45) as a prognostic indicator after NAC followed by esophagectomy. However, further research is needed to firmly establish the usefulness and reliability of PNI.


Acknowledgements

None.


Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.


References

  1. Yoshida N, Harada K, Baba Y, et al. Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer. Langenbecks Arch Surg 2017;402:333-41. [Crossref] [PubMed]
  2. Toyokawa T, Kubo N, Tamura T, et al. The pretreatment Controlling Nutritional Status (CONUT) score is an independent prognostic factor in patients with resectable thoracic esophageal squamous cell carcinoma: results from a retrospective study. BMC Cancer 2016;16:722. [Crossref] [PubMed]
  3. Feng JF, Chen QX. Significance of the prognostic nutritional index in patients with esophageal squamous cell carcinoma. Ther Clin Risk Manag 2014;10:1-7. [PubMed]
  4. Nozoe T, Kimura Y, Ishida M, et al. Correlation of pre-operative nutritional condition with post-operative complications in surgical treatment for oesophageal carcinoma. Eur J Surg Oncol 2002;28:396-400. [Crossref] [PubMed]
  5. Kuroda D, Sawayama H, Kurashige J, et al. Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer 2017. [Epub ahead of print]. [Crossref] [PubMed]
  6. Tokunaga R, Sakamoto Y, Nakagawa S, et al. CONUT: a novel independent predictive score for colorectal cancer patients undergoing potentially curative resection. Int J Colorectal Dis 2017;32:99-106. [Crossref] [PubMed]
  7. Kanda M, Fujii T, Kodera Y, et al. Nutritional predictors of postoperative outcome in pancreatic cancer. Br J Surg 2011;98:268-74. [Crossref] [PubMed]
  8. Okamura Y, Ashida R, Ito T, et al. Preoperative neutrophil to lymphocyte ratio and prognostic nutritional index predict overall survival after hepatectomy for hepatocellular carcinoma. World J Surg 2015;39:1501-9. [Crossref] [PubMed]
  9. Onodera T, Goseki N, Kosaki G. Prognostic nutritional index in gastrointestinal surgery of malnourished cancer patients. Nihon Geka Gakkai Zasshi 1984;85:1001-5. [PubMed]
  10. Cao X, Zhao G, Yu T, et al. Preoperative Prognostic Nutritional Index Correlates with Severe Complications and Poor Survival in Patients with Colorectal Cancer Undergoing Curative Laparoscopic Surgery: A Retrospective Study in a Single Chinese Institution. Nutr Cancer 2017;69:454-63. [Crossref] [PubMed]
  11. Harada K, Ida S, Baba Y, et al. Prognostic and clinical impact of sarcopenia in esophageal squamous cell carcinoma. Dis Esophagus 2016;29:627-33. [Crossref] [PubMed]
  12. Watanabe M, Ishimoto T, Baba Y, et al. Prognostic impact of body mass index in patients with squamous cell carcinoma of the esophagus. Ann Surg Oncol 2013;20:3984-91. [Crossref] [PubMed]
  13. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:2074-84. [Crossref] [PubMed]
  14. Allum WH, Stenning SP, Bancewicz J, et al. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol 2009;27:5062-7. [Crossref] [PubMed]
  15. Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 2012;19:68-74. [Crossref] [PubMed]
  16. Fukuda T, Seto Y, Yamada K, et al. Can immune-enhancing nutrients reduce postoperative complications in patients undergoing esophageal surgery? Dis Esophagus 2008;21:708-11. [Crossref] [PubMed]
  17. Mazaki T, Ishii Y, Murai I. Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a multiple-treatments meta-analysis. Ann Surg 2015;261:662-9. [Crossref] [PubMed]
  18. Brown RE, Abbas AE, Ellis S, et al. A prospective phase II evaluation of esophageal stenting for neoadjuvant therapy for esophageal cancer: optimal performance and surgical safety. J Am Coll Surg 2011;212:582-8. [Crossref] [PubMed]
  19. Bower M, Jones W, Vessels B, et al. Nutritional support with endoluminal stenting during neoadjuvant therapy for esophageal malignancy. Ann Surg Oncol 2009;16:3161-8. [Crossref] [PubMed]
  20. Hiura Y, Takiguchi S, Yamamoto K, et al. Effects of ghrelin administration during chemotherapy with advanced esophageal cancer patients: a prospective, randomized, placebo-controlled phase 2 study. Cancer 2012;118:4785-94. [Crossref] [PubMed]
  21. Fuhrman MP. The albumin-nutrition connection: separating myth from fact. Nutrition 2002;18:199-200. [Crossref] [PubMed]
  22. Kondrup J, Rasmussen HH, Hamberg O, et al. a new method based on an analysis of controlled clinical trials. Clin Nutr 2003;22:321-36. [Crossref] [PubMed]
  23. Detsky AS, McLaughlin JR, Baker JP, et al. What is subjective global assessment of nutritional status? JPEN J Parenter Enteral Nutr 1987;11:8-13. [Crossref] [PubMed]
Cite this article as: Yoshida N, Baba Y, Baba H. Preoperative malnutrition and prognosis after neoadjuvant chemotherapy followed by subsequent esophagectomy. J Thorac Dis 2017;9(10):3437-3439. doi: 10.21037/jtd.2017.09.02