Abstract
Background/Aim: Post-gastrectomy lean body mass (LBM) decrease has a significant negative impact on postoperative survival in patients with cancer. This study investigated the effect of intake of at least one-third of the daily protein requirement at breakfast on the maintenance of LBM in patients during the first month post-gastrectomy. Patients and Methods: Among patients with gastric cancer who underwent curative distal gastrectomy between April 2011 and December 2018, without adjuvant chemotherapy, we evaluated 401 patients who had consumed more than the daily protein requirement in the first month postoperatively, using the FFQW82 nutrition intake questionnaire. Patients were divided into those who consumed more (≥1/3 intake group, n=160) and those who consumed less than one-third of the daily protein requirement at breakfast (<1/3 intake group, n=241). We compared the LBM reduction rate at one month postoperatively between groups. Univariate and multivariate analyses were performed to determine clinicopathological factors predicting LBM reduction at one month postoperatively. Results: The LBM reduction rate at one month post-curative distal gastrectomy was significantly higher in the <1/3 intake group than in the ≥1.3 intake group (p=0.01) at breakfast. Multivariate analysis showed that morning protein intake below one-third of the daily requirement independently predicted LBM reduction (odds ratio=1.75, 95% confidence interval=1.14-2.68, p<0.01). Conclusion: Consuming at least one-third of the daily protein requirement at breakfast may be effective in maintaining LBM in patients undergoing curative distal gastrectomy. These results may be very important for prognosis, since maintaining LBM influences the continuation of adjuvant chemotherapy and thus survival after curative resection in patients with gastric cancer.
Gastric cancer (GC) was the fifth most commonly diagnosed cancer worldwide in 2022, with 968,000 new cases and 660,000 cancer-related deaths (1). Among patients with gastric cancer, the standard treatment for locally advanced gastric cancer is radical resection followed by adjuvant chemotherapy. Postoperative adjuvant chemotherapy significantly impacts the survival of patients with advanced gastric cancer (2-5), indicating the importance of continuing adjuvant chemotherapy postoperatively to improve survival (6, 7). To continue adjuvant chemotherapy, prevention of postoperative weight loss and loss of lean body mass (LBM, excluding fat) is important in patients with gastric cancer. Weight loss >15% or LBM loss >5% in the first month postsurgery for gastric cancer has been reported to hamper adjuvant chemotherapy continuation (8, 9). Furthermore, a decrease in postoperative skeletal muscle mass per se has been reported to be a poor prognostic factor in gastric cancer (10).
The relationship between circadian rhythms and hormone secretion, metabolism, and disease, including cancer, has been reported previously (11-13). Furthermore, chrononutrition, the study of the relationship between circadian rhythms and nutritional function, has attracted attention (14). Chrononutrition investigates the effects of diet on the body, focusing on the time axis, with the aim of contributing to disease prevention and improving physical and mental activity. Nutrients reset the circadian clock of peripheral cells in the human body. Moreover, the effects of a high-fat diet on the body vary depending on the time of day of intake (15, 16). Moreover, adequate protein intake at breakfast has been shown to be essential for the maintenance of muscle mass (17, 18). Effective nutritional intake is extremely important for post-gastrectomy patients, but no studies investigating effective chrononutrition-based nutrition in patients with gastric cancer who have undergone gastrectomy have been reported to date.
In this study, we investigated the effect of breakfast protein intake in maintaining LBM in patients with gastric cancer who had undergone curative distal gastrectomy. We divided patients into two groups based on breakfast protein intake: those who consumed at least one-third of the daily protein requirement and those who consumed less than one-third of the daily protein requirement during the first month postsurgery.
Patients and Methods
Eligible patients. Patients were retrospectively selected from the medical database of the Department of Gastroenterological Surgery, Kanagawa Cancer Center, Yokohama, Japan, according to the following inclusion criteria: histologically proven adenocarcinoma according to the Japanese classification of gastric cancer (19); pathological stage according to the International Union Against Cancer TNM 8th edition (20) [(p)I or IIA (pT1 and pN2) or (pT3 and pN0)]; patients who underwent curative resection (R0 resection) between April 2011 and December 2018 and did not receive postoperative adjuvant chemotherapy; body composition analysis performed within one week before and one month after surgery; patients who received nutrition counseling within one week before and one month after surgery and completed a questionnaire regarding nutritional intake (FFQW82). However, patients with grade 2 or higher postoperative complications, patients who underwent subtotal gastrectomy, and patients whose total daily protein intake was below the estimated average daily requirement (0.72 g/kg) stated by the Ministry of Health, Labor, and Welfare (21) were excluded from the study.
The study was approved by the Institutional Review Board of Kanagawa Cancer Center, Yokohama, Japan (2023-epidemiology-131), and details of the study were published on the website to afford patients the opportunity to opt-out of participation in the study. All procedures followed in this study were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent for inclusion in the study was obtained from all patients by the opt-out method.
Surgical technique and perioperative care. All patients underwent curative distal gastrectomy with lymph node dissection and reconstruction by Billroth-I or Roux-en-Y methods according to Japanese guidelines for the treatment of gastric cancer (22). Perioperatively, patients were managed using the Enhanced Recovery After Surgery protocol (23). Thus, patients were allowed to eat until midnight the day before surgery and were given two 500 ml bottles of oral rehydration solution to consume up to 3 hours before surgery. Postoperative oral intake commenced with drinking water on the second postoperative day; solid food commenced with rice gruel and soft foods on the third postoperative day, and regular meals were started in three stages on the seventh postoperative day. Patients were discharged after the seventh postoperative day if their food intake was more than half of the preoperative level and if their laboratory data were normal, after checking their preoperative exercise capacity.
Nutritional counseling by a dietitian. Patients in this study received nutrition counseling by a dietitian one week prior to surgery, on the day of admission, the day of discharge, and one month after surgery. During the counseling one week prior to surgery, the dietitian analyzed the patients’ preoperative dietary intake and determined their weight and body composition. During the discharge counseling, the dietitian educated the patients on how to eat after gastrectomy, including increasing the amount of food but decreasing the amount of food per meal, and eating slowly and chewing well. During the first postoperative month, the dietitian analyzed the patients’ postoperative food intake using the FFQW82 (24), described below, and measured their weight and body composition.
Questionnaire on nutritional intake using FFQW82. The FFQW82 is a nutritional intake questionnaire reported by Watanabe et al. (24). The FFQW82 is a self-administered questionnaire that asks about the frequency of intake of 82 foods, presented in 16 food groups, and about the portion size of each meal. Frequency of intake is indicated in six categories (0: never, 1: 1-2 times a month, 2: 1-2 times a week, 3: 3-4 times a week, 4: 5-6 times a week, 5: daily). Three portion sizes (small, medium, and large), which are bite-sized intakes, are indicated. Standard amounts for medium are shown by size on the food list with pictures. Small is defined as half the amount of medium and large as 1.5 times the amount of medium. The FFQW82 is designed to be completed by the patients themselves in approximately 30 min. We identified the estimated protein intake for each meal based on the patient’s own FFQW82 responses.
Relationship between protein intake at breakfast and the rate of decrease in LBM at one month after surgery. Using the MC-190EM bioelectrical impedance analyzer (Tanita Corporation, Tokyo, Japan), which provides relative information on body composition and hydration status, LBM was measured at one week before and one month after surgery, and the LBM reduction rate at one month after surgery was calculated as: [(preoperative LBM – one month postoperative LBM)/preoperative LBM]×100 (%). The median cutoff for the rate of decrease in LBM at one month postoperatively was 3.76%. We then compared the LBM reduction rate at one month after distal gastrectomy, dividing the patients into those whose protein intake at breakfast was at least one-third of the required daily intake (≥1/3 intake group: n=160) and those whose intake was less than one-third of this requirement (<1/3 intake group: n=241).
Statistical analysis. Fisher’s exact test was used to compare patient backgrounds in the ≥1/3 intake group and the <1/3 intake group. Logistic regression analysis of patient background, including postoperative breakfast protein intake, preoperative clinicopathological factors, and surgical factors, was used to identify predictors of decreased LBM in the first postoperative month. We included factors that had p<0.1 in univariate analysis as well as clinically important factors that may influence the decrease in LBM in multivariate analysis to identify factors affecting postoperative LBM reduction. Two-sided p-values <0.05 were considered significant. All statistical analyses were performed using SPSS Statistics software ver. 25 (IBM, Armonk, NY, USA).
Results
Eligible patients. At our hospital, 598 patients with gastric cancer underwent distal gastrectomy from April 2011 to December 2018 and were diagnosed as pStage I, IIA (pT1, pN2) or (pT3, pN0), and did not undergo adjuvant chemotherapy. Of these, 47 patients for whom body composition was not measured preoperatively or 30 days postoperatively, 35 patients who did not respond to the FFQW82 within 30-days postoperatively, 93 patients with postoperative complications of grade 2 or higher, four patients with pathologically diagnosed neuroendocrine cancer, four patients with a total daily protein intake below the daily requirement, and 14 patients who underwent subtotal gastrectomy were excluded from the study. The remaining 401 patients were included in the study (Figure 1).
Flow diagram of patient enrolment in this study. Of 598 patients who underwent distal gastrectomy from April 2011 to December 2018, who were diagnosed as pStage IA/IB/IIA, and who did not receive adjuvant chemotherapy, 401 patients were finally included in the present study.
Comparison of clinicopathological characteristics between the ≥1/3 and the <1/3 breakfast protein intake groups. Table I shows the patient characteristics and the association between morning protein intake and clinicopathologic features, including pathological and surgical findings. The study included 241 men (60.1%) and 160 women (39.9%) with a median age of 67 years [IQR (interquartile range)=60–73 years]. The proportion of men and women was the same in both groups, but the proportion of patients over 75 years of age was significantly higher in the ≥1/3 intake group (p=0.01). Preoperative body mass index and preoperative albumin levels were not significantly different between the two groups. The percentage of patients with decreased LBM in the first postoperative month and the rate of decrease in LBM were significantly higher in the <1/3 intake group (p=0.03). Pathology and surgical findings did not differ between the two groups.
Patient characteristics and association between gastric shape and clinicopathological features.
Univariate and multivariate logistic regression analysis of predictors of LBM loss. Clinicopathologic factors are summarized in Table II. Univariate analysis showed that males, use of Roux-en-Y reconstruction, and intake of less than one-third of the daily protein requirement were significant risk factors for LBM loss. Multivariate analysis similarly showed that men [odds ratio (OR)=2.78, 95% confidence interval (CI)=1.81-4.28, p<0.001], use of Roux-en-Y reconstruction (OR=1.75, 95%CI=1.07-2.87, p=0.02), and intake of less than one-third of the daily protein requirement (OR=1.75, 95%CI=1.14-2.68, p<0.01) were independent predictors of LBM loss.
Univariate and multivariate logistic regression analyses of predictive factors for the loss of lean mass body (LBM).
Discussion
In this study, to verify the importance of adequate protein intake at breakfast in patients with gastric cancer who underwent curative gastrectomy, patients were divided into two groups by their protein intake at breakfast during the first month after surgery: those who consumed at least one-third of the required daily intake and those who consumed less than one-third of the required daily intake. We found that the rate of decrease in LBM at one month postoperatively was lower in the group consuming at least one-third of the daily protein intake than in the group consuming less than one-third of the daily protein intake. This indicates that morning protein intake may be effective for muscle maintenance in patients who have undergone gastrectomy.
Previous reports on weight and LBM after distal gastrectomy have reported an 8.8% decrease in weight and a 4.1% decrease in LBM by one month postoperatively (9, 25). These reports suggested that a decrease in LBM by one month after gastrectomy may be a risk factor for worse continuation of adjuvant chemotherapy (9, 25). In addition, weight loss and LBM reduction per se have recently been reported to worsen the prognosis of various cancers (10, 26). Thus, maintenance of postoperative weight and LBM in gastric cancer is crucial from a therapeutic outcome standpoint.
Since muscle protein synthesis is induced by dietary protein, protein intake is important for the maintenance of LBM and muscle mass (27). Although daily protein intake is important for muscle synthesis, factors such as the quality and distribution of daily protein intake have recently been reported to be more related to muscle synthesis, and the benefit of morning protein intake has been reported (17). Several genes associated with muscle synthesis and breakdown have been identified as having circadian rhythms, and similar rhythms may exist in muscle synthesis. For example, the expression of MyoD, a gene involved in muscle differentiation, has a circadian rhythm regulated by clock genes and has been reported to be greatly influenced by diet (28). Furthermore, it has been reported that morning protein intake may improve insulin sensitivity and may stimulate muscle synthesis (29). These mechanisms suggest that breakfast protein intake may be effective in maintaining LBM after gastrectomy in gastric cancer patients.
Study limitations. First, this was a retrospective, single-center cohort study. The results of this study need to be validated in a large multicenter prospective study. Second, we do not know if all of the supplemental foods that patients may have eaten were reported. Third, although no information on the exercise status of the patients were available in this study, it is likely that the amount of exercise did not vary markedly among patients, since our clinic prohibits patients from performing abdominal muscle-intensive exercises, such as strength training, for approximately one month after surgery. Fourth, this study used a bioelectrical impedance analyzer to perform a segmental analysis of body composition, including not only muscle mass, but also liver and kidney mass. As visceral mass does not change after surgery, it is likely that muscle was the major contributor to changes in LBM. However, the bioelectrical impedance analyzer could not directly measure only muscle mass.
Conclusion
In conclusion, our results suggested that morning protein intake may be useful in maintaining LBM at one month after distal gastrectomy. These results may be very important for prognosis, as LBM influences the continuation of adjuvant chemotherapy and thus survival after gastrectomy in patients with gastric cancer.
Acknowledgements
The Authors thank the patients, their families, and the staff at Kanagawa Cancer Center for their participation in this study.
Footnotes
Authors’ Contributions
Study concept and study design: SN. Data collection and literature search: SN, HA, MT, YN, SO, JM, IH, HS, MN, TY, TO, NY, AS, and TO. Data analysis and interpretation: SN, and TO. Draft manuscript and figure preparation: SN, and TO. The final manuscript was revised and approved by all investigators. All Authors actively participated in this study.
Funding
No financial support was provided for this study.
Conflicts of Interest
None of the Authors have any conflicts of interest to declare regarding this study.
- Received August 23, 2024.
- Revision received September 16, 2024.
- Accepted September 17, 2024.
- Copyright © 2024 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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