Next Article in Journal
Association between High-Fat Diet during Pregnancy and Heart Weight of the Offspring: A Multivariate and Mediation Analysis
Next Article in Special Issue
Sensitivity and Specificity of Body Mass Index for Sarcopenic Dysphagia Diagnosis among Patients with Dysphagia: A Multi-Center Cross-Sectional Study
Previous Article in Journal
Antioxidant Efficacy of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Elderly Subjects: A Randomized, Double Blind, Controlled Study
Previous Article in Special Issue
Association of Existence of Sarcopenia and Poor Recovery of Swallowing Function in Post-Stroke Patients with Severe Deglutition Disorder: A Multicenter Cohort Study
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 14
Issue 20
10.3390/nu14204236
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Preoperative High Visceral Fat Increases Severe Complications but Improves Long-Term Prognosis after Gastrectomy for Patients with Advanced Gastric Cancer: A Propensity Score Matching Analysis

by
Ryota Matsui
1,2,*,
Noriyuki Inaki
1,2,
Toshikatsu Tsuji
1,2,
Yoji Kokura
3 and
Ryo Momosaki
4
1
Department of Gastroenterological Surgery, Ishikawa Prefectural Central Hospital, 2-1 Kuratsuki-higashi, Kanazawa 920-8530, Ishikawa, Japan
2
Department of Gastrointestinal Surgery/Breast Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa 920-8641, Ishikawa, Japan
3
Department of Nutritional Management, Keiju Hatogaoka Integrated Facility for Medical and Long-Term Care, Hosu 927-0023, Ishikawa, Japan
4
Department of Rehabilitation Medicine, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Mie, Japan
*
Author to whom correspondence should be addressed.
Nutrients 2022, 14(20), 4236; https://doi.org/10.3390/nu14204236
Submission received: 29 August 2022 / Revised: 27 September 2022 / Accepted: 8 October 2022 / Published: 11 October 2022
(This article belongs to the Special Issue Rehabilitation Nutrition in Older People)
Browse Figures
Review Reports Versions Notes

Abstract

:
This study investigated the paradox of high visceral fat mass increasing severe complications but improving long-term prognosis after radical gastrectomy for gastric cancer. This was a retrospective cohort study of consecutive patients with primary stage I–III gastric cancer who underwent gastrectomy between April 2008 and June 2018. The visceral adipose tissue index (VAI) was calculated by dividing the visceral fat mass preoperatively measured on computed tomography by the square of the height. Patients with VAIs below the median cut-off value were classified as low-VAI, while those above it were classified as high-VAI. We compared the postoperative complication rate and overall survival (OS) in the low- and high-VAI groups after adjusting patient characteristics using propensity score matching (PSM). There were 155 patients in both groups after PSM. After matching, there was no significant difference in factors other than BMI and VAI that were not adjusted. The high-VAI group had more severe postoperative complications (p = 0.018), but the OS was significantly better in the high-VAI group (hazard ratio 0.611, 95%CI 0.403–0.928, p = 0.021). Preoperative high visceral fat mass not only increased severe complications, but also improved OS after gastrectomy in patients with advanced gastric cancer.

1. Introduction

In patients with gastric cancer, preoperative body composition has recently been shown to be a useful measure of postoperative complications following gastrectomy. When visceral fat content is high, infectious complications such as pancreatic fistula, intraabdominal abscess, anastomotic leakage, and wound infection increase [1,2,3,4,5,6,7,8,9,10]. The reason for this is that the greater the amount of visceral fat, the longer the operating time, the greater the amount of intraoperative blood loss, and the greater the difficulty of the operation [7,11,12]. Indeed, obese patients with c-stage I gastric cancer and metabolic syndrome who underwent gastrectomy after a one-month preoperative exercise program experienced a decrease in visceral fat mass and postoperative complications [13]. This suggests that having low visceral fat before surgery may help to prevent complications.
On the other hand, there is still no certain consensus on the impact of visceral fat content on long-term prognosis after gastrectomy in gastric cancer patients. According to reports, postoperative complications following a gastrectomy are linked to a poor long-term prognosis [14], and complications that are severe have a worse prognosis [15]. A high visceral fat content increases postoperative complications and may result in a poor long-term prognosis following gastrectomy. In cancer patients, obesity has been linked to the development of cancer [16], although paradoxical associations with prolonged long-term survival have also been observed [17]. Among cancers, the prognosis of lung and colorectal cancer is improved by obesity [18,19], while it has been linked to a poor prognosis in breast cancer, pancreatic cancer, and hepatocellular carcinoma [20,21,22]. Since obesity is a global issue, it is crucial to comprehend how visceral fat mass affects a patient’s long-term prognosis following gastrectomy for gastric cancer.
In this study, we investigated postoperative complications and overall survival (OS) in advanced gastric cancer according to preoperative visceral fat mass. We hypothesized that a high preoperative visceral fat content would increase postoperative complications and lead to poor OS in patients with advanced gastric cancer.

2. Materials and Methods

2.1. Study Design

This was a single-institution, retrospective cohort study conducted at Ishikawa Prefectural Central Hospital, which included consecutive patients who underwent gastrectomy for primary stage I–III gastric cancer, diagnosed according to the 15th edition of the Japanese Classification of Gastric Carcinoma, between April 2008 and June 2018. Clinical and laboratory data, including medical records and images, were collected retrospectively using the hospital’s electronic patient record system. As an inclusion criterion, we considered three factors: (1) primary gastric cancer; (2) gastrectomy; and (3) computed tomography (CT) images preoperatively. The following patients were excluded: (1) pathologically diagnosed early gastric cancer, (2) residual gastric cancer, (3) cancers of other organs, (4) preoperative treatment, (5) pStage IV, (6) non-gastrectomy surgical procedures, and (7) insufficient CT imaging data. The patients who met the criteria outlined above were divided into two groups based on their visceral fat levels. Using propensity score matching (PSM), we compared postoperative outcomes between the two groups after adjusting for patient background.

2.2. Postoperative Chemotherapy

The S-1 postoperative adjuvant chemotherapy regimen begun at 80–120 mg/m2 per day in p-stage II–III and reduced in accordance with recommendations if side effects were detected. S-1 postoperative chemotherapy was administered for a maximum of a year, and no additional therapy was provided until recurrence. In accordance with the Japanese Gastric Cancer Treatment Guidelines, chemotherapy was given to patients who experienced recurrences.
The outpatient clinic conducted patient follow-ups. Hematological tests were performed at least once every two to three weeks while receiving S-1 treatment and at least once every three months for five years after treatment finished. For the first five years after surgery, patients received an endoscopy once a year and a CT scan every six months. After relapse, patients underwent a CT scan every two to three months.

2.3. Body Composition Analysis

Using the graphic analysis software Ziostation (ZIOSOFT, Tokyo, Japan), we assessed the amount of skeletal muscle and visceral fat on preoperative CT scans. Skeletal muscle mass was assessed at the level of the third lumbar vertebra, whereas visceral fat mass was assessed at the umbilical level. We calculated the visceral adipose tissue index (VAI) and skeletal muscle mass index (SMI) by dividing visceral fat and skeletal muscle mass measured in a single slice by the square of height in m2 [1].
Cut-off values for VAI and SMI were determined separately for men and women based on the median values. The cut-off value for VAI was 35.98 cm2/m2 for men and 28.61 cm2/m2 for women. Patients whose VAIs were below and above the cut-off value were classified as low-VAIs and high-VAIs, respectively. The cut-off values for SMI were 42.06 cm2/m2 for men and 33.85 cm2/m2 for women. Additionally, patients with an SMI below and above the cut-off value were classified as having a low or high SMI, respectively.

2.4. Outcomes

The primary outcome was overall survival (OS), with secondary outcomes including cancer-specific survival (CSS), other-cause survival (OCS), disease-free survival (DFS), total number of postoperative complications, severe postoperative complications, infectious complications, and postoperative body weight loss (BWL). The OS is the period between surgery and death. The DFS is the period between surgery and recurrence or death. OCS is the period between surgery and non-cancer death. Postoperative complications of Clavien-Dindo (CD) classification grade 2 or higher were recorded as those occurring within 30 days after surgery. CD grade 3 or higher was considered a severe complication. The BWL rate was measured at 1 month, 6 months, and 1 year postoperatively.

2.5. Statistical Analyses

We used PSM to account for differences in patient background and to reduce selection bias. A logistic regression model with the following covariates was used to evaluate the propensity score: sex, age, surgical procedure, surgical approach, clinical stage, comorbidities, lymph node dissection, and SMI; body mass index (BMI) and VAI were excluded. The nearest-neighbor matching method was used, and the two groups were matched one-to-one. The caliper size was 0.20. After matching, we compared the postoperative outcomes between the two groups. The Mann–Whitney U test was used to compare patient characteristics and postoperative outcomes for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. We used the log-rank test for Kaplan–Meier survival analyses. To identify prognostic factors for OS, we used a forward stepwise procedure of Cox proportional hazards regression for multivariate analysis and calculated hazard ratios (HRs). EZR software was used to perform all statistical analyses, which is based on R (The R Foundation for Statistical Computing, Vienna, Austria) and R commander [23]. The statistical significance was set at p < 0.05.

3. Results

3.1. Patient Background

This study’s flowchart is shown in Figure 1. A total of 417 patients met the eligibility criteria, and 209 (50.1%) and 208 (49.9%) were assigned to the low- and high-VAI groups, respectively. Following PSM, both groups had 155 patients. Patient background is shown in Table 1. Before matching, the high-VAI group had a higher BMI (p < 0.001), a greater number of patients with diabetes (p = 0.018), a higher SMI (p < 0.001), and a higher VAI (p < 0.001). After matching, there was no significant difference in factors other than BMI and VAI that were not adjusted.

3.2. Comparison of Postoperative Outcomes after Matching

The postoperative outcomes after matching are shown in Table 2. There was no difference in pathological findings, operating time, and intraoperative blood loss. A higher number of severe postoperative complications were reported in the high-VAI group (p = 0.026). BWL rates were significantly higher in the high-VAI group at 6 months and 1 year (p < 0.001 and p < 0.001, respectively). There was no difference in the rate of postoperative chemotherapy, but the completion rate for one year was significantly higher in the high-VAI group (p = 0.007).

3.3. Long-Term Outcomes According to VAI after Matching

The median duration of follow-up was 48 months (interquartile range, 21–60 months). The OS was significantly better in the high-VAI group (HR 0.611, 95%CI 0.403–0.928, p = 0.021). There was no difference in the OCS (HR 0.691, 95%CI 0.331–1.440, p = 0.323), but the CSS was significantly better for the high-VAI group (HR 0.563, 95%CI 0.339–0.933, p = 0.026). The DFS was better in the high-VAI group (HR 0.678, 95%CI 0.470–0.977, p = 0.037) (Figure 2).

3.4. Long-Term Outcomes According to Severe Complications after Matching

The OS was worse in the severe complications group (HR 2.223, 95%CI 1.295–3.816, p = 0.004) (Figure 3a). The OS rates, stratified for both VAI and severe complications, are shown in Figure 3b. Patients with high-VAI without severe complications had the best survival rates, and patients with low-VAI with severe complications had the worst survival rates (p = 0.005).

3.5. Long-Term Outcomes Stratified by VAI and pStage after Matching

The OS rates, stratified for both VAI and pStage, are shown in Figure 4. In pStage III, patients with high-VAI had better survival rates than patients with low-VAI (p < 0.001).

3.6. Prognostic Factors for OS

The results of multivariate analysis with forward stepwise procedure of the prognostic factors for OS in all patients without matching are shown in Table 3. Multivariate analysis showed that age ≥ 70 years (HR = 2.101, 95%CI 1.399–3.155, p < 0.001), open surgery (HR 2.091, 95%CI 1.411–3.098, p < 0.001), pStage ≥ III (HR 4.110, 95%CI 1.411–3.098, p < 0.001), postoperative chemotherapy (HR 0.492, 95%CI 0.315–0.767, p = 0.002), diabetes (HR 1.580, 95%CI 1.013–2.465, p = 0.044), severe postoperative complications (HR 1.791, 95%CI 1.085–2.958, p = 0.023), and high-VAI (HR 0.457, 95%CI 0.307–0.680, p < 0.001) were independent prognostic factors for OS.

4. Discussion

In this study of patients with advanced gastric cancer, a comparison of the two groups after background adjustment using PSM revealed that preoperative high visceral fat was associated not only with an increase in severe complications but also with an increase in infectious complications. However, both OS and DFS were better in the high visceral fat group despite an increase in postoperative complications, which indicates the existence of an obesity paradox in advanced gastric cancer patients. The results of the multivariate analysis support these findings. This is the first report to show that despite the heightened risk of postoperative complications, increased visceral fat retains an advantage in long-term prognosis.
In the comparison of long-term prognosis, OS and CSS were significantly better in the high-VAI group, and DFS was better. The prognosis in the group with severe complications was worse than that in the group without severe complications. In a stratified analysis, high-VAI without severe complications had the best prognosis. High-VAI with severe complications, low-VAI with severe complications, and low-VAI without severe complications had similar prognoses. These results indicate that high-VAI is a favorable prognostic factor, and that although severe complications are a poor prognostic factor, severe complications may counteract their positive impact on prognosis.
Obesity, customarily defined by BMI, has been previously examined in relation to prognosis in gastric cancer with conflicting results. While some studies showed that a high BMI did not affect prognosis [24,25,26], others showed that a BMI over 25 kg/m2 was associated with either a poor prognosis [27] or a good prognosis [28]. This discrepancy may be due to the difficulty in determining whether a patient has a high muscle mass or a high visceral fat mass based on BMI alone. Indeed, visceral adiposity has been shown to be more useful than BMI in predicting postoperative complications [2,7,9], and body composition assessment is considered to be more accurate in predicting postoperative outcomes.
Regarding the relationship between visceral fat mass and prognosis, Harada et al. [29] reported in a study of 507 patients, half with esophageal cancer and half with gastric cancer that low visceral fat, measured by preoperative CT, was associated with poor prognosis. This is because low visceral fat mass may be an indicator of undernutrition, whereas high visceral fat mass is a rich source of energy that can be replenished. One of the reasons visceral fat mass is associated with a good prognosis is because of the extensive and persistent postoperative BWL, which is unique to gastrectomy. After gastrectomy, BWL persists for up to 6 months, during which time skeletal muscle mass decreases, mainly during the immediate postoperative period and up to approximately 3 months, and is replaced by adipose tissue thereafter [29,30,31,32,33,34]. The skeletal muscle mass loss is particularly prominent in the first week [31], followed by visceral fat-center changes in body composition, which are understood as metabolic changes that maintain muscle mass. The greater the rate of postoperative weight loss, the worse the compliance with postoperative treatment [35] and the poorer the survival [36,37,38]. Regarding visceral fat mass, Park et al. [39] reported that a large postoperative loss of visceral fat mass was associated with a poor prognosis. These results suggest that visceral fat mass reflects the amount of energy stored in the whole body, and low preoperative fat or large postoperative fat loss indicates nutritional depletion, leading to a poor prognosis.
BWL was significantly greater in the high-VAI group at 6 months and up to 1 year, while there was no difference in the rate up to 1 month postoperatively. This means that there was no difference in the rate of skeletal muscle mass loss in the acute phase, but there was a difference in the time when visceral fat mass decreased. This is thought to reflect the difference in body size before surgery and may be the result of adjusting for the skeletal muscle mass in the PSM to create a model in which only the visceral fat mass was different. Although it has been reported that the greater the postoperative weight loss, the worse the prognosis [36,37,38], the long-term prognosis was better in the high-VAI group, which had a greater weight loss. This indicates that the positive impact of preoperative visceral fat mass on long-term prognosis is greater than the negative impact of postoperative weight loss.
Regarding the choice of method to measure visceral fat mass, while BMI is a convenient method for determining obesity, it is difficult to distinguish between skeletal muscle mass, visceral fat, and subcutaneous fat using BMI alone. A CT scan has the advantage of evaluating body components separately. CT scans are the gold standard for measuring visceral fat mass [40], and recently, there have been an increasing number of reports of body composition assessed by CT. Kobayashi et al. showed that a single slice of visceral fat area measured at the umbilical level correlated strongly with the overall visceral fat mass [41]. Therefore, the measurement of visceral fat mass in a single slice in this study is likely to reflect visceral fat mass accumulation in the whole body. Since the cut-off value for skeletal muscle mass has been examined using height-corrected indexes [42], visceral fat mass was also calculated using height correction in this study. We used the median as the cut-off value for comparison between the two groups, although there is no validated cut-off value for visceral fat in gastric cancer patients.
The limitations of this study include the following: (1) the fact that it was a single-center retrospective cohort study, (2) the fact that there was no postoperative nutritional support, (3) racial differences, and (4) cut-off values for visceral fat. Only patients with insufficient dietary intake received oral nutrition supplementation in this study. It is also necessary to consider racial differences in body size. Asians have a lower BMI and are less likely to be obese than Europeans, which could have influenced the findings. As a result, the findings must be replicated in other racial groups. Furthermore, the VAI cut-off values need to be validated in additional multicenter cohort studies. To the best of our knowledge, this is the first report showing that increased visceral fat has an advantage over risk of postoperative complications in improving long-term prognosis in patients with gastric cancer who exhibit postoperative BWL. Our results suggest that there is a high need for postoperative nutritional support in the low-VAI group, while the high-VAI group requires preoperative nutritional intervention and prehabilitation to prevent postoperative complications. In the future, we would like to investigate whether a support system that includes exercise and nutritional intervention for preoperative weight loss in the high-VAI group and postoperative nutritional support in the low-VAI group will lead to longer DFS and OS.

5. Conclusions

Preoperative high visceral fat mass increased postoperative infectious and severe complications, while at the same time improved OS after gastrectomy in patients with advanced gastric cancer.

Author Contributions

Conceptualization, R.M. (Ryota Matsui) and N.I.; methodology, R.M. (Ryota Matsui), N.I., T.T., Y.K. and R.M. (Ryo Momosaki); formal analysis, R.M. (Ryota Matsui); investigation, R.M. (Ryota Matsui) and T.T.; data curation, R.M. (Ryota Matsui) and T.T.; writing—original draft preparation, R.M. (Ryota Matsui) and N.I.; writing—review and editing, R.M. (Ryota Matsui), N.I., T.T., Y.K. and R.M. (Ryo Momosaki); visualization, R.M. (Ryota Matsui), N.I., T.T., Y.K. and R.M. (Ryo Momosaki); supervision, N.I., Y.K. and R.M. (Ryo Momosaki). All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Ishikawa Prefectural Central Hospital (authorization number: 1748).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The datasets generated and/or analyzed during the current study are available upon reasonable request from the corresponding author.

Acknowledgments

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Zhang, Y.; Wang, J.P.; Wang, X.L.; Tian, H.; Gao, T.T.; Tang, L.M.; Tian, F.; Wang, J.W.; Zheng, H.J.; Zhang, L.; et al. Computed tomography-quantified body composition predicts short-term outcomes after gastrectomy in gastric cancer. Curr. Oncol. 2018, 25, e411–e422. [Google Scholar] [CrossRef] [Green Version]
  2. Yang, S.-J.; Li, H.-R.; Zhang, W.-H.; Liu, K.; Zhang, D.-Y.; Sun, L.-F.; Chen, X.-L.; Zhao, L.-Y.; Chen, X.-Z.; Yang, K.; et al. Visceral fat area (VFA) superior to BMI for predicting postoperative complications after radical gastrectomy: A prospective cohort study. J. Gastrointest. Surg. 2020, 24, 1298–1306. [Google Scholar] [CrossRef] [PubMed]
  3. Sugisawa, N.; Tokunaga, M.; Tanizawa, Y.; Bando, E.; Kawamura, T.; Terashima, M. Intra-abdominal infectious complications following gastrectomy in patients with excessive visceral fat. Gastric Cancer 2012, 15, 206–212. [Google Scholar] [CrossRef] [Green Version]
  4. Sato, Y.; Inokuchi, M.; Otsuki, S.; Fujimori, Y.; Kojima, K. Risk factor of pancreatic fistula after radical gastrectomy from the viewpoint of fatty pancreas. Dig. Surg. 2017, 34, 455–461. [Google Scholar] [CrossRef]
  5. Tokunaga, M.; Hiki, N.; Fukunaga, T.; Ogura, T.; Miyata, S.; Yamaguchi, T. Effect of individual fat areas on early surgical outcomes after open gastrectomy for gastric cancer. Br. J. Surg. 2009, 96, 496–500. [Google Scholar] [CrossRef]
  6. Kunisaki, C.; Makino, H.; Takagawa, R.; Sato, K.; Kawamata, M.; Kanazawa, A.; Yamamoto, N.; Nagano, Y.; Fujii, S.; Ono, H.A.; et al. Predictive factors for surgical complications of laparoscopy-assisted distal gastrectomy for gastric cancer. Surg. Endosc. 2009, 23, 2085–2093. [Google Scholar] [CrossRef] [PubMed]
  7. Miyaki, A.; Imamura, K.; Kobayashi, R.; Takami, M.; Matsumoto, J. Impact of visceral fat on laparoscopy-assisted distal gastrectomy. Surgeon 2013, 11, 76–81. [Google Scholar] [CrossRef] [PubMed]
  8. Yoshikawa, K.; Shimada, M.; Kurita, N.; Iwata, T.; Nishioka, M.; Morimoto, S.; Miyatani, T.; Komatsu, M.; Mikami, C.; Kashihara, H. Visceral fat area is superior to body mass index as a predictive factor for risk with laparoscopy-assisted gastrectomy for gastric cancer. Surg. Endosc. 2011, 25, 3825–3830. [Google Scholar] [CrossRef]
  9. Takeuchi, M.; Ishii, K.; Seki, H.; Yasui, N.; Sakata, M.; Shimada, A.; Matsumoto, H. Excessive visceral fat area as a risk factor for early postoperative complications of total gastrectomy for gastric cancer: A retrospective cohort study. BMC Surg. 2016, 16, 1–7. [Google Scholar] [CrossRef] [Green Version]
  10. Wang, S.-L.; Ma, L.-L.; Chen, X.-Y.; Zhou, N.-L.; Li, B.; Huang, D.-D.; Yu, Z.; Shen, X.; Zhuang, C.-L. Impact of visceral fat on surgical complications and long-term survival of patients with gastric cancer after radical gastrectomy. Eur. J. Clin. Nutr. 2018, 72, 436–445. [Google Scholar] [CrossRef] [PubMed]
  11. Shin, H.J.; Son, S.Y.; Cui, L.H.; Byun, C.; Hur, H.; Lee, J.H.; Kim, Y.C.; Han, S.U.; Cho, Y.K. Is there any role of visceral fat area for predicting difficulty of laparoscopic gastrectomy for gastric cancer? J. Gastric Cancer 2015, 15, 151–158. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Ueda, J.; Ichimiya, H.; Okido, M.; Kato, M. The impact of visceral fat accumulation on laparoscopy-assisted distal gastrectomy for early gastric cancer. J. Laparoendosc. Adv. Surg. Tech. 2009, 19, 157–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Cho, H.; Yoshikawa, T.; Oba, M.S.; Hirabayashi, N.; Shirai, J.; Aoyama, T.; Hayashi, T.; Yamada, T.; Oba, K.; Morita, S.; et al. Matched pair analysis to examine the effects of a planned preoperative exercise program in early gastric cancer patients with metabolic syndrome to reduce operative risk: The Adjuvant Exercise for General Elective Surgery (AEGES) study group. Ann. Surg. Oncol. 2014, 21, 2044–2050. [Google Scholar] [CrossRef] [PubMed]
  14. Wang, S.; Xu, L.; Wang, Q.; Li, J.; Bai, B.; Li, Z.; Wu, X.; Yu, P.; Li, X.; Yin, J. Postoperative complications and prognosis after radical gastrectomy for gastric cancer: A systematic review and meta-analysis of observational studies. World J. Surg. Oncol. 2019, 17, 1–10. [Google Scholar] [CrossRef] [Green Version]
  15. Jiang, N.; Deng, J.Y.; Ding, X.W.; Zhang, L.; Liu, H.G.; Liang, Y.X.; Liang, H. Effect of complication grade on survival following curative gastrectomy for carcinoma. World J. Gastroenterol. 2014, 20, 8244–8252. [Google Scholar] [CrossRef] [PubMed]
  16. Colditz, G.A.; Peterson, L.L. Obesity and cancer: Evidence, impact, and future directions. Clin. Chem. 2018, 64, 154–162. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Lennon, H.; Sperrin, M.; Badrick, E.; Renehan, A.G. The obesity paradox in cancer: A Review. Curr. Oncol. Rep. 2016, 18, 1–8. [Google Scholar] [CrossRef] [Green Version]
  18. Li, S.; Wang, Z.; Huang, J.; Fan, J.; Du, H.; Liu, L.; Che, G. Systematic review of prognostic roles of body mass index for patients undergoing lung cancer surgery: Does the ‘obesity paradox’ really exist? Eur. J. Cardiothorac. Surg. 2017, 51, 817–828. [Google Scholar] [CrossRef]
  19. Caan, B.J.; Meyerhardt, J.A.; Kroenke, C.H.; Alexeeff, S.; Xiao, J.; Weltzien, E.; Feliciano, E.C.; Castillo, A.L.; Quesenberry, C.P.; Kwan, M.L.; et al. Explaining the obesity paradox: The association between body composition and colorectal cancer survival (C-SCANS Study). Cancer Epidemiol. Biomark. Prev. 2017, 26, 1008–1015. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  20. Jiralerspong, S.; Goodwin, P.J. Obesity and breast cancer prognosis: Evidence, challenges, and opportunities. J. Clin. Oncol. 2016, 34, 4203–4216. [Google Scholar] [CrossRef]
  21. Okumura, S.; Kaido, T.; Hamaguchi, Y.; Kobayashi, A.; Shirai, H.; Yao, S.; Yagi, S.; Kamo, N.; Hatano, E.; Okajima, H.; et al. Visceral adiposity and sarcopenic visceral obesity are associated with poor prognosis after resection of pancreatic cancer. Ann. Surg. Oncol. 2017, 24, 3732–3740. [Google Scholar] [CrossRef] [PubMed]
  22. Fujiwara, N.; Nakagawa, H.; Kudo, Y.; Tateishi, R.; Taguri, M.; Watadani, T.; Nakagomi, R.; Kondo, M.; Nakatsuka, T.; Minami, T.; et al. Sarcopenia, intramuscular fat deposition, and visceral adiposity independently predict the outcomes of hepatocellular carcinoma. J. Hepatol. 2015, 63, 131–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Kanda, Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013, 48, 452–458. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Bickenbach, K.A.; Denton, B.; Gonen, M.; Brennan, M.F.; Coit, D.G.; Strong, V.E. Impact of obesity on perioperative complications and long-term survival of patients with gastric cancer. Ann. Surg. Oncol. 2013, 20, 780–787. [Google Scholar] [CrossRef] [PubMed]
  25. Chen, H.; Sui, W. Influence of obesity on short- and long-term outcomes after laparoscopic distal gastrectomy for gastric cancer. J. BUON 2017, 22, 417–423. [Google Scholar] [PubMed]
  26. Struecker, B.; Biebl, M.; Dadras, M.; Chopra, S.; Denecke, C.; Spenke, J.; Heilmann, A.-C.; Bahra, M.; Sauer, I.; Pratschke, J.; et al. The impact of obesity on outcomes following resection for gastric cancer. Dig. Surg. 2017, 34, 133–141. [Google Scholar] [CrossRef]
  27. Kambara, Y.; Yuasa, N.; Takeuchi, E.; Miyake, H.; Nagai, H.; Yoshioka, Y.; Okuno, M.; Miyata, K. Overweight or obesity is an unfavorable long-term prognostic factor for patients who underwent gastrectomy for stage II/III gastric cancer. World J. Surg. 2019, 43, 1766–1776. [Google Scholar] [CrossRef]
  28. Shimada, S.; Sawada, N.; Ishiyama, Y.; Nakahara, K.; Maeda, C.; Mukai, S.; Hidaka, E.; Ishida, F.; Kudo, S.-E. Impact of obesity on short- and long-term outcomes of laparoscopy assisted distal gastrectomy for gastric cancer. Surg. Endosc. 2018, 32, 358–366. [Google Scholar] [CrossRef]
  29. Harada, K.; Baba, Y.; Ishimoto, T.; Kosumi, K.; Tokunaga, R.; Izumi, D.; Ida, S.; Imamura, Y.; Iwagami, S.; Miyamoto, Y.; et al. Low visceral fat content is associated with poor prognosis in a database of 507 upper gastrointestinal cancers. Ann. Surg. Oncol. 2015, 22, 3946–3953. [Google Scholar] [CrossRef]
  30. Abdiev, S.; Kodera, Y.; Fujiwara, M.; Koike, M.; Nakayama, G.; Ohashi, N.; Tanaka, C.; Sakamoto, J.; Nakao, A. Nutritional recovery after open and laparoscopic gastrectomies. Gastric Cancer 2011, 14, 144–149. [Google Scholar] [CrossRef]
  31. Kiyama, T.; Mizutani, T.; Okuda, T.; Fujita, I.; Tokunaga, A.; Tajiri, T.; Barbul, A. Postoperative changes in body composition after gastrectomy. J. Gastrointest. Surg. 2005, 9, 313–319. [Google Scholar] [CrossRef] [PubMed]
  32. Aoyama, T.; Yoshikawa, T.; Maezawa, Y.; Kano, K.; Hara, K.; Sato, T.; Hayashi, T.; Yamada, T.; Cho, H.; Ogata, T.; et al. A Comparison of the body composition changes between laparoscopy-assisted and open total gastrectomy for gastric cancer. Vivo 2018, 32, 1513–1518. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Aoyama, T.; Kawabe, T.; Hirohito, F.; Hayashi, T.; Yamada, T.; Tsuchida, K.; Sato, T.; Oshima, T.; Rino, Y.; Masuda, M.; et al. Body composition analysis within 1 month after gastrectomy for gastric cancer. Gastric Cancer 2016, 19, 645–650. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Yoon, D.Y.; Kim, H.K.; Kim, J.A.; Choi, C.S.; Yun, E.J.; Chang, S.K.; Park, C.H.; Lee, Y.-J. Changes in the abdominal fat distribution after gastrectomy: Computed tomography assessment. ANZ J. Surg. 2007, 77, 121–125. [Google Scholar] [CrossRef]
  35. Aoyama, T.; Yoshikawa, T.; Shirai, J.; Hayashi, T.; Yamada, T.; Tsuchida, K.; Hasegawa, S.; Cho, H.; Yukawa, N.; Oshima, T.; et al. Body weight loss after surgery is an independent risk factor for continuation of S-1 adjuvant chemotherapy for gastric cancer. Ann. Surg. Oncol. 2013, 20, 2000–2006. [Google Scholar] [CrossRef]
  36. Takayoshi, K.; Uchino, K.; Nakano, M.; Ikejiri, K.; Baba, E. Weight loss during initial chemotherapy predicts survival in patients with advanced gastric cancer. Nutr. Cancer 2017, 69, 408–415. [Google Scholar] [CrossRef]
  37. Aoyama, T.; Sato, T.; Maezawa, Y.; Kano, K.; Hayashi, T.; Yamada, T.; Yukawa, N.; Oshima, T.; Rino, Y.; Masuda, M.; et al. Postoperative weight loss leads to poor survival through poor S-1 efficacy in patients with stage II/III gastric cancer. Int. J. Clin. Oncol. 2017, 22, 476–483. [Google Scholar] [CrossRef]
  38. Hynes, O.; Anandavadivelan, P.; Gossage, J.; Johar, A.M.; Lagergren, J.; Lagergren, P. The impact of pre- and post-operative weight loss and body mass index on prognosis in patients with oesophageal cancer. Eur. J. Surg. Oncol. 2017, 43, 1559–1565. [Google Scholar] [CrossRef] [Green Version]
  39. Park, H.S.; Kim, H.S.; Beom, S.H.; Rha, S.Y.; Chung, H.C.; Kim, J.H.; Chun, Y.J.; Lee, S.W.; Choe, E.-A.; Heo, S.J.; et al. Marked loss of muscle, visceral fat, or subcutaneous fat after gastrectomy predicts poor survival in advanced gastric cancer: Single-center study from the CLASSIC trial. Ann. Surg. Oncol. 2018, 25, 3222–3230. [Google Scholar] [CrossRef]
  40. Seidell, J.C.; Bakker, C.J.; van der Kooy, K. Imaging techniques for measuring adipose-tissue distribution—A comparison between computed tomography and 1.5-T magnetic resonance. Am. J. Clin. Nutr. 1990, 51, 953–957. [Google Scholar] [CrossRef]
  41. Kobayashi, J.; Tadokoro, N.; Watanabe, M.; Shinomiya, M. A novel method of measuring intra-abdominal fat volume using helical computed tomography. Int. J. Obes. 2002, 26, 398–402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  42. Matsui, R.; Inaki, N.; Tsuji, T. Impact of preoperative muscle quality on postoperative severe complications after radical gastrectomy for gastric cancer patients. Ann. Gastroenterol. Surg. 2021, 5, 510–518. [Google Scholar] [CrossRef] [PubMed]
Nutrients 14 04236 g001 550
Figure 1. Study design.
Figure 1. Study design.
Nutrients 14 04236 g001
Nutrients 14 04236 g002 550
Figure 2. Kaplan–Meier survival curves according to visceral adipose tissue after matching. (a) For overall survival, (b) for cancer-specific survival, (c) for other-cause survival, (d) for disease-free survival.
Figure 2. Kaplan–Meier survival curves according to visceral adipose tissue after matching. (a) For overall survival, (b) for cancer-specific survival, (c) for other-cause survival, (d) for disease-free survival.
Nutrients 14 04236 g002
Nutrients 14 04236 g003 550
Figure 3. Kaplan-Meier survival curves for overall survival. (a) according to severe postoperative complications after matching; (b) stratified by visceral adipose tissue and severe postoperative complications after matching.
Figure 3. Kaplan-Meier survival curves for overall survival. (a) according to severe postoperative complications after matching; (b) stratified by visceral adipose tissue and severe postoperative complications after matching.
Nutrients 14 04236 g003
Nutrients 14 04236 g004 550
Figure 4. Kaplan–Meier survival curves for overall survival stratified by visceral adipose tissue and pathological stage after matching.
Figure 4. Kaplan–Meier survival curves for overall survival stratified by visceral adipose tissue and pathological stage after matching.
Nutrients 14 04236 g004
Table
Table 1. Patient characteristics before and after propensity score matching.
Table 1. Patient characteristics before and after propensity score matching.
All PatientsAfter Matching
Low-VAI Group
(N = 209)		High-VAI Group
(N = 208)		p ValueLow-VAI Group
(N = 155)		High-VAI Group
(N = 155)		p Value
Sex
Male
Female		140 (67.0%)
69 (33.0%)		140 (67.3%)
68 (32.7%)		1.000104 (67.1%)
51 (32.9%)		103 (66.5%)
52 (33.5%)		1.000
Age, mean ± SD67.48 ± 12.0967.91 ± 9.730.68967.99 ± 11.7467.63 ± 9.910.766
Body mass index, mean ± SD20.99 ± 2.5525.06 ± 3.12<0.00121.32 ± 2.5024.62 ± 2.99<0.001
Surgical approach
Laparoscopic surgery
Open surgery		110 (52.6%)
99 (47.6%)		117 (56.2%)
91 (43.8%)		0.49287 (56.1%)
68 (43.9%)		84 (54.2%)
71 (45.8%)		0.819
Surgical procedure
Distal gastrectomy
Proximal gastrectomy
Total gastrectomy		112 (53.6%)
11 (5.3%)
86 (41.1%)		122 (58.7%)
11 (5.3%)
75 (36.1%)		0.55185 (54.8%)
7 (4.5%)
63 (40.6%)		87 (56.1%)
9 (5.8%)
59 (38.1%)		0.812
Lymph node dissection
D1+
D2		82 (39.2%)
127 (60.8%)		101 (48.6%)
107 (51.4%)		0.06172 (46.5%)
83 (53.5%)		63 (40.6%)
92 (59.4%)		0.359
Clinical stage
I
II
III		32 (15.3%)
89 (42.6%)
88 (42.1%)		50 (24.0%)
75 (36.1%)
83 (39.9%)		0.06929 (18.7%)
62 (40.0%)
64 (41.3%)		32 (20.6%)
52 (33.5%)
71 (45.8%)		0.513
Comorbidity
CKD35 (16.7%)37 (17.8%)0.79729 (18.7%)21 (13.5%)0.280
COPD45 (21.5%)40 (19.2%)0.62737 (23.9%)27 (17.4%)0.206
Diabetes30 (14.4%)49 (23.6%)0.01828 (18.1%)26 (16.8%)0.881
CHF8 (3.8%)13 (6.2%)0.2736 (3.9%)8 (5.2%)0.786
SMI (cm2/m2), median (IQR)38.00 (32.06–43.13)41.52 (36.73–48.23)<0.00139.18 (34.20–44.21)39.16 (35.46–44.54)0.572
Low-SMI127 (60.8%)81 (38.9%)<0.00180 (51.6%)77 (49.7%)0.820
VAI (cm2/m2), median (IQR)18.18 (8.95–25.10)51.86 (42.18–66.22)<0.00119.69 (9.62–25.84)50.17 (40.98–60.74)<0.001
CHF chronic heart failure, CKD chronic kidney disease, COPD chronic obstructive pulmonary disease, IQR interquartile range, SD standard deviation, SMI skeletal muscle mass index, VAI visceral adipose tissue index.
Table
Table 2. Comparison of postoperative outcomes after matching.
Table 2. Comparison of postoperative outcomes after matching.
Low-VAI Group
(N = 155)		High-VAI Group
(N = 155)		p Value
Pathological stage
I
II
III		29 (18.7%)
62 (40.0%)
64 (41.3%)		32 (20.6%)
52 (33.5%)
71 (45.8%)		0.513
Lymph node metastasis
Absent
Present		46 (29.7%)
109 (70.3%)		41 (26.5%)
114 (73.5%)		0.613
Histological type
Differentiated
Undifferentiated		63 (40.6%)
92 (59.4%)		75 (48.4%)
80 (51.6%)		0.209
Operating time (min), median (IQR)245.0 (207.5–302.5)245.0 (197.5–325.0)0.734
Intraoperative blood loss (g), median (IQR)30.0 (10.0–145.0)40.0 (17.5–165.0)0.286
Postoperative complication
Total number of postoperative complications28 (18.1%)41 (26.5%)0.101
Severe complications10 (6.5%)23 (14.8%)0.026
Infectious complications17 (11.0%)29 (18.7%)0.078
Abdominal abscess12 (7.7%)23 (14.8%)0.072
Incisional surgical site infection3 (1.9%)5 (3.2%)0.723
Anastomotic leakage6 (3.9%)9 (5.8%)0.598
Pancreatic leakage5 (3.2%)14 (9.0%)0.056
Pneumonia6 (3.9%)7 (4.5%)1.000
Ileus5 (3.2%)5 (3.2%)1.000
Cardiovascular complications1 (0.6%)2 (1.3%)1.000
Bleeding complications1 (0.6%)5 (3.2%)0.214
Postoperative chemotherapy
Completion rate for one year		99 (63.9%)
80 (76.9%)		99 (63.9%)
94 (91.3%)		1.000
0.007
Postoperative body weight loss (%)
For 1 month, median (IQR)
For 6 months, median (IQR)
For 1 year, median (IQR)		7.52 (5.40–11.42)
10.11 (6.09–15.75)
8.87 (5.02–14.77)		8.30 (5.76–11.94)
14.33 (9.50–18.98)
15.79 (10.41–19.62)		0.451
<0.001
<0.001
Pathological stage
I
II
III		29 (18.7%)
62 (40.0%)
64 (41.3%)		32 (20.6%)
52 (33.5%)
71 (45.8%)		0.513
IQR interquartile range, VAI visceral adipose tissue index.
Table
Table 3. Result of multivariate analysis of prognostic factors for overall survival.
Table 3. Result of multivariate analysis of prognostic factors for overall survival.
VariablesMultivariate Analysis
HR95%CIp Value
Age (years)<701
2.101
1.399–3.155
<0.001
≥70
Surgical approachLaparoscopic surgery1
2.091
1.411–3.098
<0.001
Open surgery
Pathological stage<III1
4.110
2.675–6.316
<0.001
≥III
Postoperative chemotherapyAbsent1
0.492
0.315–0.767
0.002
Present
DiabetesAbsent1
1.580
1.013–2.465
0.044
Present
Postoperative complicationsAbsent1
1.791
1.085–2.958
0.023
Clavien-Dindo ≥ 3
SMI (cm2/m2)High-SMI1
1.352
0.915–1.999
0.129
Low-SMI
VAI (cm2/m2)Low-VAI1
0.457
0.307–0.680
<0.001
High-VAI
CI confidence interval, CRP C-reactive protein, HR hazard ratio, SMI skeletal muscle mass index, VAI visceral adipose tissue index.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Matsui, R.; Inaki, N.; Tsuji, T.; Kokura, Y.; Momosaki, R. Preoperative High Visceral Fat Increases Severe Complications but Improves Long-Term Prognosis after Gastrectomy for Patients with Advanced Gastric Cancer: A Propensity Score Matching Analysis. Nutrients 2022, 14, 4236. https://doi.org/10.3390/nu14204236

AMA Style

Matsui R, Inaki N, Tsuji T, Kokura Y, Momosaki R. Preoperative High Visceral Fat Increases Severe Complications but Improves Long-Term Prognosis after Gastrectomy for Patients with Advanced Gastric Cancer: A Propensity Score Matching Analysis. Nutrients. 2022; 14(20):4236. https://doi.org/10.3390/nu14204236

Chicago/Turabian Style

Matsui, Ryota, Noriyuki Inaki, Toshikatsu Tsuji, Yoji Kokura, and Ryo Momosaki. 2022. "Preoperative High Visceral Fat Increases Severe Complications but Improves Long-Term Prognosis after Gastrectomy for Patients with Advanced Gastric Cancer: A Propensity Score Matching Analysis" Nutrients 14, no. 20: 4236. https://doi.org/10.3390/nu14204236

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop