In 1994, Kitano et al. first reported laparoscopic gastrectomy (LG) [1]. Since then, use of LG has been increasing gradually [2,3,4]. Several randomized trials and meta-analyses have shown the feasibility and surgical safety of LG, along with earlier patient recovery, reduced postoperative pain, and better quality of life after LG than after open gastrectomy (OG) [5,6,7,8,9,10]. The indications for LG are expanding, including advanced gastric cancer and remnant gastric cancer [11,12,13,14].

The number of overweight people in Japan has increased dramatically in recent years, due in part to changes in lifestyle behaviors. Similarly, the number of overweight gastric cancer patients has increased in Japan [15]. Body mass index (BMI) has been commonly used as one of the most reliable indices of obesity because of its simplicity and objectivity. A high BMI is a well-known risk factor for postoperative complications after gastrectomy for gastric cancer [16,17,18,19,20]. However, BMI may not reflect the body fat distribution, that is, BMI does not correlate with visceral fat area (VFA) [21, 22]. Asians have more visceral fat than Caucasians with the same BMI [21]. Several studies have reported that high VFA is more strongly associated with longer operative time and greater intraoperative blood loss, and it is a risk factor for postoperative complications compared to high BMI for OG [23,24,25,26]. However, few reports have examined the impact of VFA on laparoscopic procedures. This study aimed to compare the impacts of preoperative VFA and preoperative BMI on outcomes of total laparoscopic resection for cancer.

Materials and methods

Patients

This was a retrospective, cohort study. From January 2015 to December 2019, a total of 587 patients with gastric cancer underwent gastrectomy at Osaka Medical College Hospital, Japan. As per the exclusion criteria, patients who underwent OG or robotic gastrectomy, had macroscopic residual disease following surgery (R2 resection), had simultaneous resection of other organs except for the gallbladder or spleen, or had remnant gastric cancer were excluded. Therefore, data from 409 patients were analyzed in the present study.

Patients’ preoperative examinations included upper gastrointestinal endoscopy, abdominal computed tomography (CT), and laboratory tests including tumor markers such as CEA and CA19-9. Gastric cancer diagnoses were based on pathological findings.

Patients’ preoperative characteristics, including age, sex, BMI, American Society of Anesthesiologists (ASA) score, pathological stage, and history of diabetes mellitus, anti-thrombotic therapy, upper abdominal surgery, and neoadjuvant chemotherapy, were retrospectively evaluated from hospital records. Pathological stage was defined by the Japanese classification of gastric carcinoma [27]. The study protocol was approved by the ethics committee of Osaka Medical and Pharmaceutical University Hospital (approval no. 2020-005), which waived the need for informed consent due to the retrospective nature of the study.

Surgical techniques

Lymph node dissection, surgical procedure, and gastric reconstruction were determined according to the Japanese gastric cancer treatment guidelines [28]. Splenectomy was performed when the tumor was located on the greater curvature of the upper third of the stomach. In our institute, almost all resections for gastric cancer were performed laparoscopically regardless of clinical stage, except for clinical trials limited to open surgery procedures and emergency surgery, such as for perforation or acute bleeding. Surgical procedures for gastric cancer consisted of laparoscopic total gastrectomy (LTG), laparoscopic distal gastrectomy (LDG), laparoscopic proximal gastrectomy (LPG), and laparoscopic pylorus-preserving gastrectomy (LPPG). All reconstruction procedures were performed intracorporeally. In LDG, intracorporeal Billroth I reconstruction with a delta-shaped mechanical anastomosis was performed. In cases of a small remnant stomach, reflux esophagitis, or elderly persons, intracorporeal Billroth II, or Roux-en-Y reconstruction was performed [4, 14]. Reconstruction of the esophagojejunostomy following LTG or double-tract LPG, esophagogastrostomy following LPG, gastrogastrostomy following LPPG, and both Billroth I and Billroth II following LDG involved side-to-side anastomosis using a linear stapler with closure of the entry hole using two unidirectional barbed sutures, but Roux-en-Y reconstruction following LDG involved both side-to-side anastomosis and closure of the entry hole using a linear stapler. Details of our procedures have been reported elsewhere [3, 4, 14, 29,30,31]. All surgeries were performed or supervised by surgeons who had performed more than 500 cases and were certified by the Japan Society for Endoscopic Surgery [32].

Definition of early surgical outcomes and postoperative complications

The primary endpoint was surgical outcomes, including operative time, intraoperative blood loss, number of retrieved lymph nodes, C-reactive protein (CRP) on postoperative day (POD) one or three, number of postoperative hospital days, and first day of flatus.

The secondary endpoint was the incidence of postoperative complications included anastomotic leakage, pancreatic fistula, intra-abdominal abscess, pneumonia, ileus, delayed gastric emptying, wound infection, anastomotic bleeding, hemorrhage, and others determined as grade II or higher complications based on the Clavien–Dindo classification [33]. Pancreatic fistula was diagnosed on the basis of the definitions of the International Study Group on Pancreatic Fistula (ISGPF) [34]. Anastomotic leakage was diagnosed by radiological examination using orally administered contrast media.

Definition of VFA and BMI

Abdominal fat distribution was analyzed on preoperative CT images at the level of the umbilicus [35] (Fig. 1). The Volume Analyzer SYNAPSE VINCENT image analysis system (Fujifilm Medical, Tokyo, Japan) was used to quantify abdominal adipose tissue area and volume. The intraperitoneal area was defined by tracing its contour automatically or manually when it was not correct on the scan. Adipose tissue was determined by setting the attenuation level within the range of − 190 to − 30 Hounsfield units [36]. VFA was quantified automatically by the software. The cutoff value for VFA was set at 100 cm2. This value is equivalent to that used in Japan for the diagnosis of metabolic syndrome, among other criteria [22]. On the other hand, the cutoff value for BMI was 25 kg/m2, because it is used in the definition of obesity of the Japan Society for the Study of Obesity [22].

Fig. 1
figure 1

Visceral fat area at the level of the umbilicus (red field) measured on preoperative computed tomography with the Volume Analyzer SYNAPSE VINCENT image analysis system

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Propensity score matching

Propensity score matching was used to reduce potential bias. Propensity scores were estimated using a logistic regression model with the following 12 factors: age, sex, ASA score, pathological stage, surgical procedure, reconstruction procedure, lymph node dissection, splenectomy, history of diabetes mellitus, anti-thrombotic therapy, upper abdominal surgery, and neoadjuvant chemotherapy. Propensity scores were matched using one-to-one nearest-neighbor matching. A caliper width of 0.2 of the standard deviation of the logit of the propensity score was used.

Statistical analysis

All statistical analyses were performed using JMP pro 15 (ver. 15, SAS Institute, Cary, NC, USA). Continuous variables are presented as means ± standard deviation (SD) and were compared using the Wilcoxon rank-sum test. The Chi-squared test and Fisher’s exact probability test were used to compare differences in the categorical variables. Spearman’s rank correlation coefficient was used to evaluate relationships between VFA and BMI. Associations of surgical outcomes with the VFA were analyzed using multiple linear regression models. Associations between postoperative complications and the variables were analyzed by logistic regression analysis. A p value of less than 0.05 was considered significant.

Perioperative management

In our institute, the Enhanced Recovery after Surgery (ERAS) protocol has been introduced in perioperative care [37]. The patients took 250 ml of oral carbohydrate solution on the night before surgery and 2 h before anesthesia. On POD 1, patients started walking and were allowed to drink clear fluids. The patients started to ingest a liquid diet on POD 2, after which the diet continued through four daily steps to eventually eating regular food on POD 6. Acetaminophen was administered orally twice daily until POD 5.

Results

Patients’ characteristics

The patient selection flowchart is shown in Fig. 2. A total of 587 patients who underwent gastrectomy for gastric cancer were reviewed. Of these, 122 patients who underwent OG, 25 who underwent robotic gastrectomy, 15 who underwent remnant gastrectomy, eight who underwent R2 resection, and eight who underwent simultaneous resection of other organs for other diseases such as colorectal cancer (n = 4), esophageal cancer (n = 1), hepatic cancer (n = 2), and endometrial cancer (n = 1) were excluded.

Fig. 2
figure 2

Flowchart of the patients assessed in this study

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Thus, 409 patients who underwent LG were enrolled in this study. In this cohort, 226 patients were in the high-VFA group, and 183 patients were in the low-VFA group. Patients’ characteristics according to VFA values are listed in Table 1. There were significant differences in sex, ASA score, and history of upper abdominal surgery. After propensity score matching, data of 144 pairs of patients were extracted. Patients’ characteristics after propensity score matching are listed in Table 2, and there were no significant differences.

Table 1 Patients’ characteristics by VFA group
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Table 2 Patients’ characteristics by VFA group after propensity score matching
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Similarly, 319 patients constituted the high-BMI group, and 90 patients constituted the low-BMI group. Patients’ characteristics according to BMI values are listed in Table 3. There were significant differences in ASA score and history of diabetes mellitus. After propensity score matching, data of 82 pairs of patients were extracted. Patients’ characteristics after propensity score matching are listed in Table 4, and there were no significant differences in their background characteristics.

Table 3 Patients’ characteristics by BMI group
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Table 4 Patients’ characteristics by BMI group after propensity score matching
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Comparison between high-VFA and low-VFA groups

Table 5 compares the surgical outcomes and postoperative complications between the high-VFA and low-VFA groups. For surgical outcomes, operative time was significantly longer and intraoperative blood loss was significantly higher in the high-VFA group than in the low-VFA group (p = 0.003, p = 0.0006; respectively). CRP levels on POD 1 and POD 3 were significantly higher in the high-VFA group (p = 0.001, p = 0.004; respectively). There were no significant differences in the number of retrieved lymph nodes, duration of postoperative hospital days, and first day of flatus between the two groups. Major postoperative complications including anastomotic leakage, pancreatic fistula, intra-abdominal abscess, and pneumonia did not differ between the high-VFA and low-VFA groups.

Table 5 Comparison of surgical outcomes and postoperative complications between the low-VFA group and the high-VFA group
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Correlation between VFA and BMI

Figure 3 shows the correlation between VFA and BMI. VFA and BMI were significantly correlated (R2 = 0.64), but the correlation was not strong. The enrolled patients in this study were divided into 4 subgroups (low VFA/low BMI, high VFA/low BMI, low VFA/high BMI, high VFA/high BMI) (Table 6). The low-VFA/low-BMI group was the most common (50.2%), followed by the high-VFA/low-BMI group (27.8%), high-VFA/high-BMI group (16.8%), and low-VFA/high-BMI group (5.1%).

Fig. 3
figure 3

Correlation between body mass index (BMI) and visceral fat area (VFA)

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Table 6 Division of the patients in this study into 4 subgroups by VFA and BMI
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Comparison between high-BMI and low-BMI groups

Table 7 compares the surgical outcomes and postoperative complications between the high-BMI and low-BMI groups. For surgical outcomes, the first day of flatus was significantly later in the high-BMI group than in the low-BMI group. Regarding postoperative complications, there were no significant differences between the two groups.

Table 7 Comparison of surgical outcomes and postoperative complications between the low-BMI group and the high-BMI group
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Relationships between VFA or BMI and surgical outcomes

The relationships between surgical outcomes and VFA were investigated by univariate and multivariate analyses. Potential confounding variables with p < 0.2 on univariate analysis were included in the multivariate analyses. Independent variables were selected from among age (continuous), sex, VFA (< 100 cm2 or ≥ 100 cm2), BMI (< 25 kg/m2 or ≥ 25 kg/m2), ASA (≤ 2 or ≥ 3) score, pathological stage (I, II or III, IV), surgical procedure (DG, PG, PPG or TG), reconstruction procedure (Billroth I or other than Billroth I), lymph node dissection (≤ D1 + or ≥ D2), splenectomy (yes or no), history of diabetes mellitus (yes or no), anti-thrombotic therapy (yes or no), upper abdominal surgery (yes or no), and neoadjuvant chemotherapy (yes or no).

The univariate and multivariate analyses of operative time are shown in Table 8. Age, sex, BMI, VFA, pathological stage, surgical procedure, reconstruction procedure, splenectomy, lymph node dissection, and preoperative chemotherapy were included as explanatory variables in the multivariate regression analyses. The VFA was an independent predictor of operative time (regression coefficient (β): 0.11, 95% confidence interval (CI) 3.5–16.27, p = 0.002).

Table 8 Univariate and multivariate analyses for operative time
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The results for intraoperative blood loss are shown in Table 9. Age, BMI, VFA, pathological stage, surgical procedure, reconstruction procedure, splenectomy, lymph node dissection, preoperative chemotherapy, diabetes mellitus, anti-thrombotic therapy, and upper abdominal surgery were included as explanatory variables in the multivariate regression analyses. VFA was not significantly associated with intraoperative blood loss on multivariate analysis (β: 0.01, 95% CI − 5.88 to 8.25, p = 0.74).

Table 9 Univariate and multivariate analyses for intraoperative blood loss
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On the other hand, regarding the BMI, there were no significant relationships with operative time (β: 0.04, 95% CI − 2.94–11.66, p = 0.24) and intraoperative blood loss (β: 0.07, 95% CI − 2.19–14.67, p = 0.14).

Univariate and multivariate analyses of postoperative complications

The results of univariate and multivariate analyses of postoperative complications are shown in Table 10. Age, sex, VFA, pathological stage, and reconstruction procedures were included as explanatory variables in the multiple logistic regression analyses. VFA was not a risk factor for postoperative complications (odds ratio (OR): 1.407, 95% CI 0.894–2.218, p = 0.13).

Table 10 Univariate and multivariate analyses for postoperative complications
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Discussion

The results of the present study showed that high VFA may be more related to longer operative time than high BMI following LG. However, even in patients with high VFA, although operative time was longer, there were no significant differences in postoperative complications compared with low VFA.

In the present study, no similar conclusion was obtained in the BMI group because BMI does not reflect body fat distribution, such as visceral fat and subcutaneous fat. In the present study, VFA and BMI were not strongly correlated. Approximately 30% of enrolled patients had normal BMI (< 25 kg/m2) but high VFA (≥ 100 cm2). The effect of visceral fat is stronger than that of subcutaneous fat in laparoscopic surgery.

Some reports showed that, with high VFA, the operative time was significantly longer [38,39,40], the intraoperative blood loss was significantly increased [39, 40], and the number of retrieved lymph nodes was significantly decreased [38, 41] than with high BMI. However, these reports were derived from a surgical procedure of LDG, not including other gastric resections. There are two reports including surgical procedures besides LDG. Liu et al. reported that VFA better evaluated the operative time and the risk of postoperative complications than BMI [42]. Shin et al. reported that VFA might be a better predictive marker than BMI for operative time and intraoperative blood loss [43]. These reports involved laparoscopic-assisted gastrectomy (LAG) with extracorporeal reconstruction through minilaparotomy. That is, there have been no reports about pure LG. Okabe et al. reported that the incidence of postoperative complications after gastrectomy increased in proportion to the VFA [44]. This report included open and laparoscopic approaches. To the best of our knowledge, the present study was the first evaluate the contributions of VFA and BMI for predicting surgical outcomes and postoperative complications in total LG using propensity score matching.

The reason why patients with high VFA may have difficulty with gastrectomy is that lymph nodes are embedded in thick fat tissue and are hard to distinguish when surrounded by fat, making lymph node dissection difficult. In addition, excessive visceral fat leads to a poor visual operative field, causing vulnerable organization and increased ease of bleeding, naturally leading to longer operative time and increased intraoperative blood loss. However, due to the progress of energy devices such as laparoscopic coagulating shears or vessel sealing systems in recent years, hemostatic ability has improved; so, although intraoperative blood loss has increased significantly, it is considered to be within the acceptable range with high VFA (mean: 27 ml with high VFA). Therefore, high VFA was not an independent risk factor for intraoperative blood loss. In addition, endoscopic images have been sharpened, and the magnifying effect enables the recognition of fat layers and the lymph node dissection along the outermost layer, which refers to the dissectible layer around the artery [45], so that lymph node dissection is possible without decreasing the number of retrieved lymph nodes.

CRP levels on both POD 1 and POD 3 were significantly higher in the high-VFA group than in the low-VFA group. Iida et al. only reported that patients with high VFA have high CRP levels after laparoscopic-assisted gastrectomy compared with low VFA with or without postoperative complications and suggested that visceral fat might promote the postoperative inflammatory response [46]. Fontane et al. reported that interleukin-6 concentrations were significantly higher in the portal vein of obese patients who underwent open gastric bypass surgery and suggested that visceral fat itself is a source of inflammation [47]. The present study showed similar results, but in addition to that consideration, it is also considered that postoperative invasion, such as longer operative time and greater intraoperative blood loss, increases the CRP level. From the clinical perspective, even if the postoperative CRP level is high, if the physical findings are unremarkable, there is no need to start antibiotics or delay oral intake based on suspicion of complications such as infection.

It was interesting that a high VFA had no effect on postoperative complications in the present study. However, several studies have reported that high VFA is more strongly associated with postoperative complications following OG [23,24,25,26]. For overweight patients undergoing OG, anastomotic leakage may occur due to the deep surgical field with the high subcutaneous fat that is difficult to anastomose. Furthermore, with LAG as well, the anastomosis is performed through a minilaparotomy made in the epigastrium. There is often difficulty performing the anastomosis in the narrow and restricted space, especially for overweight patients with high subcutaneous fat. However, this effect of high subcutaneous fat is relatively small in total LG with intracorporeal anastomosis. Esophagojejunostomy after LTG is generally a difficult procedure, but it can be performed safely with the recent improvements in the technique of laparoscopic surgery in terms of the incidence of anastomotic leakage (JCOG1401) [48]. With the improvement of the automatic suturing device and the use of barbed sutures, intracorporeal esophagojejunostomy can be performed with greater safety [29]; therefore, high VFA does not lead to an increased risk of anastomotic leakage.

The reason why pancreatic fistulas may occur in OG with high VFA is that excessive visceral fat makes it difficult to find the border between the pancreas and lymph nodes, which may result in pancreatic injury during lymph node dissection. However, the border between the pancreas and lymph nodes can be recognized by improving the endoscopic image and the magnifying effect; therefore, as for anastomotic leakage, high VFA does not lead to increased pancreatic fistulas. Similar to VFA, there was no significant difference between the high-BMI and low-BMI groups. High BMI includes obesity, in which there is much subcutaneous fat, not visceral fat. Subcutaneous fat does not increase pancreatic fistulas in laparoscopic surgery.

There were no significant differences in the number of postoperative hospital days for both the VFA and BMI groups. Liu et al. reported that patients with high VFA had longer hospital stays, which indicated that high VFA would delay the postoperative recovery of patients [42]. However, we previously reported that the ERAS protocol shortened the postoperative hospital stay after gastrectomy for gastric cancer [37]; it did not lead to delayed postoperative recovery of patients in both the high-VFA and high-BMI groups. Similarly, there were no significant differences in postoperative complications such as pneumonia, ileus, and delayed gastric emptying. The fact that these complications did not increase may be due to the ERAS protocol. The first day of flatus was only delayed in the high-BMI group, but there is a possibility that postoperative ambulation was less in the high-BMI group than in the low-BMI group. However, it was not enough to lead to postoperative complications such as ileus and longer postoperative hospital stay.

There are several limitations to the present study. First, it was performed at a single institution in Japan, and the cutoff value for BMI was 25 kg/m2 according to the Japan Society for the Study of Obesity [22]. To define obesity, most countries use standards set by the World Health Organization (WHO), which defines overweight as a BMI of more than 25 kg/m2, and obesity as a BMI of 30 kg/m2 and above. Those levels are based largely on data from Caucasian populations. About 30% of Americans have a BMI of more than 30 kg/m2, but only a few Asians, less than 5%, have a BMI of more than 30 kg/m2. However, whereas a high proportion (30%) of Americans are obese, only 8% have diabetes mellitus, a rate on par with that in Asia [49]. Asians are thought to be prone to metabolic syndrome even with mild obesity. Therefore, it is used in the definition of obesity of the Japan Society for the Study of Obesity [22]. However, a BMI of more than 25 kg/m2 is very common among Americans, and it would be useful to examine whether there are any differences among overweight, obese, morbidly obese, and super-obese patients. However, even in the present study, only 2% of cases had a BMI of more than 30 kg/m2, which does not allow proper statistical analysis. Furthermore, Asians are more prone to visceral fat obesity than Caucasians [21]; therefore, the reproducibility of the results requires evaluation in other medical centers and racial groups. Second, there may have been unmeasurable confounding risk factors. However, most major risk factors for surgical outcomes and postoperative complications were included. In addition, men and women should be evaluated separately in order to evaluate the effects of abdominal shape on short-term surgical outcomes. However, dividing the patients by sex would decrease the number of patients in each analysis. In particular, in the present study, the sample size of females was small, they had few complications, and there were no significant differences between two groups. Therefore, we compared and examined the two groups using propensity score-matched analysis so that there would be no difference Thus, we believe that this minimized the effects of unmeasurable confounders. Third, operations were performed or supervised by surgeons certified by the Japan Society for Endoscopic Surgery and well experienced in LG for gastric cancer. Shin et al. reported that VFA accumulation was associated with technical difficulties for surgeons who had performed fewer than 50 cases of LG for gastric cancer [43]. Further retrospective studies are needed to confirm the impact of VFA on outcomes of LG for inexperienced surgeons to show real-world evidence. Fourth, there was no effect on short-term outcomes, and long-term outcomes, including survival rates, could not be addressed. Long-term follow-up is required in future studies. Tan et al. reported that long-term survival following LG was not significantly different between obese patients and non-obese patients [50]. In the present study, lymph node dissection was possible without decreasing the number of retrieved lymph nodes in the high-VFA group, and pathological stage was equivalent between the high-VFA group and the low-VFA group before the propensity score-matched analysis. That is, it is considered that no difference in long-term outcomes could be expected.

Conclusion

In conclusion, VFA is a better indicator of longer operative time than BMI. However, accumulation of VFA did not affect short-term outcomes, except for the duration of surgery.