Frailty, Immunonutrition, Surgery Type, and Biologic Recovery in Elderly Gastric Cancer

This prospective, observational, analytical cohort study will be conducted at the General Surgery Clinic of Kocaeli City Hospital. The study will include patients aged 60 years and older who have gastric cancer and are scheduled for elective radical gastrectomy. A total of 328 patients are planned to be enrolled.

Preoperative assessment will include multidimensional frailty-related parameters, including the modified Frailty Index-11 (mFI-11), Montreal Cognitive Assessment (MoCA), handgrip strength, Nutritional Risk Screening 2002 (NRS-2002), Prognostic Nutritional Index (PNI), and skeletal muscle characteristics assessed on computed tomography at the L3 level. Baseline neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels will also be recorded.

Intraoperative data will include surgical approach, operative duration, and intraoperative blood loss. Postoperatively, NLR and CRP will be assessed on postoperative days 1, 3, and 5. Delirium will be evaluated using the Confusion Assessment Method (CAM). Postoperative complications will be recorded according to the Clavien-Dindo classification, together with hospital length of stay and handgrip strength before discharge.

The primary purpose of the study is to evaluate the association between multidimensional frailty phenotypes and postoperative outcomes and biological recovery in older patients undergoing gastric cancer surgery. The study will also investigate whether the surgical approach is associated with differences in biological recovery among patients with different frailty profiles.

• Laparoscopic Gastrectomy (Procedure): Elective radical gastrectomy performed using a laparoscopic approach as part of routine clinical care. The surgical approach is not assigned by the study
• Open Gastrectomy (Procedure): Elective radical gastrectomy performed using an open approach as part of routine clinical care. The surgical approach is not assigned by the study

Primary outcomes

• Rate of postoperative complication [Up to 30 days post-operative]: According to the Clavien-Dindo classification, the status of postoperative complications during index hospitalisation.

Secondary outcomes

• Comparison of Changes in the Neutrophil-to-Lymphocyte Ratio (NLR) [Preoperative baseline, day 1 post-operative, day 3 post-operative, day 5 post-operative]: Change in neutrophil-to-lymphocyte ratio from preoperative baseline to postoperative days 1, 3, and 5

Other outcomes

• Changes in C-reactive protein (CRP) levels during the postoperative period compared with baseline values [Preoperative baseline, day 1 post-operative, day 3 post-operative, day 5 post-operative]: Change in C-reactive protein from preoperative baseline to postoperative days 1, 3, and 5.
• Rate of postoperative delirium [Day 1 post-operative, day 2 post-operative, day 3 post-operative, day 4 post-operative, day 5 post-operative.]: Occurrence of postoperative delirium assessed daily using the Confusion Assessment Method.
• Comparison of length of stay in hospital [From date of surgery until date of hospital discharge, assessed up to 3 months]: Hospital length of stay measured in days from surgery to hospital discharge.
• Comparison of changes in hand grip strength [Baseline, pre-discharge]: Change in handgrip strength from the preoperative assessment to the pre-discharge assessment

Sex: All, ages: 60 Years to any

Inclusion Criteria:

* Age 60 years or older.
* Histopathological or endoscopic diagnosis of gastric cancer.
* Planned elective radical gastrectomy.
* Written informed consent to participate in the study.

Exclusion Criteria:

* Stage IV metastatic gastric cancer.
* Requirement for emergency surgery.
* Severe neurological or psychiatric disease preventing completion of cognitive testing.
* Incomplete clinical data.
* Refusal to participate in the study.

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. PMID 33538338
• Japanese Gastric Cancer Association. Gastric cancer treatment guidelines 2021. Gastric Cancer. 2022;25:1-21.
• Makary MA, Segev DL, Pronovost PJ, Syin D, Bandeen-Roche K, Patel P, Takenaga R, Devgan L, Holzmueller CG, Tian J, Fried LP. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010 Jun;210(6):901-8. doi: 10.1016/j.jamcollsurg.2010.01.028. Epub 2010 Apr 28. PMID 20510798
• Ethun CG, Bilen MA, Jani AB, et al. Frailty and cancer surgery outcomes. Ann Surg Oncol. 2017;24:2131-2139.
• McIsaac DI, Taljaard M, Bryson GL, Beaule PE, Gagne S, Hamilton G, Hladkowicz E, Huang A, Joanisse JA, Lavallee LT, MacDonald D, Moloo H, Thavorn K, van Walraven C, Yang H, Forster AJ. Frailty as a Predictor of Death or New Disability After Surgery: A Prospective Cohort Study. Ann Surg. 2020 Feb;271(2):283-289. doi: 10.1097/SLA.0000000000002967. PMID 30048320
• Shimada H, Makizako H, Lee S, Doi T, Lee S, Tsutsumimoto K, Harada K, Hotta R, Bae S, Nakakubo S, Harada K, Suzuki T. Impact of Cognitive Frailty on Daily Activities in Older Persons. J Nutr Health Aging. 2016;20(7):729-35. doi: 10.1007/s12603-016-0685-2. PMID 27499306
• Partridge JS, Harari D, Martin FC, Dhesi JK. The impact of pre-operative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review. Anaesthesia. 2014 Jan;69 Suppl 1:8-16. doi: 10.1111/anae.12494. PMID 24303856
• Jia G, Li K. Prognostic Nutritional Index is A Useful Predictive Marker for Morbidity and Mortality in Surgery for Perforated Peptic Ulcer. J Inflamm Res. 2025 Aug 14;18:11021-11028. doi: 10.2147/JIR.S519037. eCollection 2025. PMID 40831514
• Kanasaki H, Oride A, Miyazaki K. Laparoscopic surgery in elderly patients aged 65 years and older with gynecologic disease. ISRN Obstet Gynecol. 2012;2012:678201. doi: 10.5402/2012/678201. Epub 2012 Nov 21. PMID 23227353
• Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752-62. doi: 10.1016/S0140-6736(12)62167-9. Epub 2013 Feb 8. PMID 23395245

• Adem Yuksel, Assoc.Prof., Principal investigator, Kocaeli City Hospital