ABSTRACT
Aim
Minimally invasive surgery (MIS) is increasingly used for gastric cancer surgery. MIS is expected to facilitate surgical precision because of its magnified view, and facilitating identification of anatomical dissection layers is expected to reduce postoperative complications. To our knowledge, there is no consensus on the most appropriate surgical approach for gastric cancer following chemotherapy.
Methods
This nationwide, observational study used data from the National Clinical Database. Patients who underwent total gastrectomy (TG) or distal gastrectomy (DG) for gastric cancer after receiving chemotherapy between January 2014 and December 2022 were included. The incidence of overall complications of Clavien‐Dindo (CD) grade ≥ 1 was set as the primary outcome, and the risk ratio (RR) was estimated using inverse probability of treatment weighting based on propensity scores and G‐computation, comparing MIS and open surgery. The incidence of each complication was considered the secondary outcome.
Results
Overall, 18 100 patients were included in this study (TG, 9481; DG, 8619). MIS was associated with a lower incidence of overall complications of CD grade ≥ 1 in both TG (RR 0.91, 95% confidence interval [CI] 0.85–0.98) and DG (RR 0.78, 95% CI 0.72–0.84). MIS was also significantly associated with a lower incidence of superficial incisional surgical site infection (SSI), deep incisional SSI, and pancreatic fistulas in both gastrectomy groups.
Conclusions
MIS was associated with lower rates of overall postoperative complications of CD grade ≥ 1, and wound‐related complications and pancreatic fistulas than open surgery in patients with gastric cancer who underwent TG and DG after chemotherapy.
Keywords: gastrectomy, laparoscopy, postoperative complications, stomach neoplasms
This nationwide observational study used data from the National Clinical Database. Patients who underwent total or distal gastrectomy for gastric cancer after chemotherapy between January 2014 and December 2022 were included. Minimally invasive surgery was associated with lower incidences of overall postoperative complications of Clavien–Dindo grade ≥ 1, superficial and deep incisional surgical site infections, and pancreatic fistulas than open surgery.
1. Introduction
Gastric cancer treatment is tailored to the disease stage and includes endoscopic resection, surgery, chemotherapy, immunotherapy, and radiotherapy. For locally advanced or Stage IV gastric cancer, surgery is often performed after chemotherapy, such as neoadjuvant chemotherapy (NAC), followed by gastrectomy or conversion surgery [1]. However, to our knowledge, there is no consensus on the most appropriate surgical approach for gastric cancer following chemotherapy.
Gastric cancer has traditionally been treated with open surgery. Minimally invasive surgery for gastric cancer was first reported by Kitano et al. in 1994 [2]. Because small incisions offer greater cosmetic benefits and less postoperative pain, leading to faster recovery, they have now become widely adopted in clinical practice [3, 4]. Furthermore, in 2003, Hashizume et al. reported that robotic gastrectomy and minimally invasive surgery have become the standard approaches for gastric cancer operations [5]. Besides smaller incisions, minimally invasive surgery is expected to facilitate surgical precision because of the magnified view it provides, facilitating identification of accurate dissection layers and performing appropriate lymph node dissection, which is expected to reduce postoperative complications [6, 7].
In patients with gastric cancer who have undergone chemotherapy, changes occur that are not observed in those who do not receive preoperative chemotherapy, leading to a higher risk of complications [8, 9]. Patient‐related factors include deterioration of nutritional and immune status due to chemotherapy and bone marrow suppression. From a surgical perspective, the difficulty of surgery increases because of tissue fibrosis, which obscures the dissection planes around the blood vessels and pancreas. Thus, both patient and tumor factors contribute to an increased risk of postoperative complications in gastric cancer surgery following chemotherapy. Minimally invasive surgery, with its precise techniques, may reduce postoperative complications, even in challenging cases; however, there have been few reports on this topic. Therefore, this study summarized the surgical outcomes of patients who underwent total or distal gastrectomy after chemotherapy for gastric cancer and conducted a comparative analysis of postoperative complications.
2. Materials and Methods
2.1. Study Design and Setting
This nationwide observational study used the National Clinical Database (NCD) data. This study included patients who underwent total or distal gastrectomy for gastric cancer after receiving chemotherapy between January 2014 and December 2022. Because detailed data on preoperative chemotherapy were not collected, it was not possible to distinguish between surgeries performed after NAC and conversion surgeries for unresectable gastric cancer. Patients aged < 18 years and those who had undergone emergency surgery were excluded. Minimally invasive and open surgeries were compared. Perioperative and postoperative observation items included anesthesia time, operation time, intraoperative blood loss, intraoperative fluid volume, postoperative hospital stay, intraoperative blood transfusion, intraoperative events, readmission within 30 days after surgery, and residual cancer. The primary outcome was the incidence of overall postoperative complications (grade ≥ 1), selected to comprehensively assess postoperative morbidity after gastrectomy. The secondary outcomes were the incidence of overall postoperative complications (grade ≥ 2 and grade ≥ 3) and individual complications. Postoperative complications were assessed according to the Clavien‐Dindo (CD) classification [10]. Postoperative pancreatic fistula was defined as clinically relevant postoperative pancreatic fistula (Grade B or C) according to the International Study Group of Pancreatic Surgery classification [11].
This study was approved by the Ethics Committee of Kyoto University (ID: R4101). The need for informed consent was waived because of the anonymity of the study data; however, the opportunity to withdraw consent through an opt‐out process was guaranteed.
2.2. Statistical Analysis
Categorical variables are presented as numbers and percentages, and continuous variables are summarized as medians and interquartile ranges (IQR). A descriptive comparison of patient backgrounds, surgical outcomes, and postoperative complications between the minimally invasive and open surgery groups was conducted. Cases with missing values were excluded, and a complete case analysis was conducted.
Inverse Probability of Treatment Weighting (IPTW) was performed to minimize treatment selection bias and confounding factors in the comparison of postoperative complications between minimally invasive and open surgeries. The analysis was conducted using the average Treatment Effect on the Treated (ATT), effect estimation by G‐computation, and standard errors by M‐estimation. Propensity scores were calculated based on age, sex, body mass index (BMI), diabetes, smoking, habitual drinking, dyspnea, activities of daily living, artificial respiration, chronic obstructive pulmonary disease, pneumonia, ascites, hypertension, congestive heart failure, myocardial infarction, angina pectoris, acute renal failure, hemodialysis, cerebrovascular disease, advanced metastatic cancer, long‐term steroid use, weight loss, bleeding risk factors, preoperative blood transfusion, sepsis, American Society of Anesthesiologists–Physical Status, radiation therapy, immunotherapy, cT, cN, and cM. Covariates with only one observed category were excluded from the propensity scoring model. Covariate balance after weighting was evaluated using standardized mean differences (SMD), with an absolute SMD of < 0.1 indicating adequate balance.
For each binary postoperative complication, an outcome regression model was fitted under ATT weights, and treatment effects were obtained using G‐computation. Treatment‐specific risks were obtained using marginal standardization. Risk ratios (RRs; primary measure) and risk differences (RDs) with 95% confidence intervals (CIs) were estimated, and standard errors were computed using M‐estimation. Treatment–covariate interaction terms in the outcome model were evaluated, but when sparse data led to numerical instability or implausibly wide CIs, interaction terms were omitted; in such cases, treatment‐specific risks were presented as reference values. Outcomes with model‐fitting errors owing to very low event counts were excluded. p values were two‐sided, and statistical significance was set at p < 0.05.
Statistical analyses were performed using R software (version 4.3.3). IPTW weights were estimated using the weightit() function in the WeightIt package (v1.2.0), and covariate balance was assessed using SMD, referring to the bal.tab() function in the cobalt package (v4.5.5). Weighted outcome models were fitted using the glm_weightit() function in the WeightIt package (v1.2.0), and treatment‐specific risk and effect estimates were obtained using the avg_predictions() and avg_comparisons() functions in the Marginaleffects package (v0.21.0).
3. Results
3.1. Patient Characteristics Before IPTW
Between January 2014 and December 2022, 537 469 gastric cancer patients were registered in the NCD. Among these, 35 787 patients received preoperative chemotherapy, and 19 054 underwent total or distal gastrectomy. After excluding patients involving emergency surgery, duplicate registrations, patients aged < 18 years, and those with missing values for the evaluation items and covariates, 18 100 patients were included in this study (total gastrectomy, 9481; distal gastrectomy, 8619) (Figure 1). The numbers and proportions of missing values for each variable are presented in Table S1. The annual trends in the numbers of open and minimally invasive surgeries are presented in Table S2. Because laparoscopic and robotic surgery could be distinguished from 2018 onward, their annual trends are presented in Table S3.
FIGURE 1.
Flow diagram of patient selection.
The patient characteristics are shown in Table 1. Among the patients who underwent total gastrectomy, the proportion of patients with advanced cancer and multiple metastases, preoperative weight loss, preoperative blood transfusion, and cT4, cN3, and cM1 was lower in the minimally invasive surgery group than in the open surgery group. No apparent differences were observed in the other patient backgrounds between the two groups. Among the patients who underwent distal gastrectomy, the proportion of those with low BMI, advanced cancer and multiple metastases, preoperative weight loss, preoperative blood transfusion, and cT4, cN3, and cM1 levels was lower in the minimally invasive surgery group than in the open surgery group. Conversely, the proportion of patients who received preoperative radiotherapy or immunotherapy was higher in the minimally invasive surgery group. No differences were observed between the two groups with respect to other patient backgrounds.
TABLE 1.
Patient characteristics.
| Factor | Category | Total gastrectomy | Distal gastrectomy | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MIS (n = 2225) | Open (n = 7256) | SMD | MIS (n = 2803) | Open (n = 5816) | SMD | ||||||
| n | % | n | % | n | % | n | % | ||||
| Age (years) | < 70 | 1176 | 52.9 | 3950 | 54.4 | 0.03 | 1219 | 43.5 | 2737 | 47.1 | 0.07 |
| ≥ 70 | 1049 | 47.1 | 3306 | 45.6 | −0.03 | 1584 | 56.5 | 3079 | 52.9 | −0.07 | |
| Sex | Male | 1554 | 69.8 | 5276 | 72.7 | 0.06 | 1961 | 70 | 4195 | 72.1 | 0.05 |
| Female | 671 | 30.2 | 1980 | 27.3 | −0.06 | 842 | 30 | 1621 | 27.9 | −0.05 | |
| Body mass index | < 18.5 | 376 | 16.9 | 1400 | 19.3 | 0.06 | 430 | 15.3 | 1093 | 18.8 | 0.10 |
| 18.5 ≤, < 25 | 1501 | 67.5 | 4915 | 67.7 | 0.01 | 1928 | 68.8 | 3902 | 67.1 | −0.04 | |
| ≥ 25 | 348 | 15.6 | 941 | 13 | −0.07 | 445 | 15.9 | 821 | 14.1 | −0.05 | |
| Diabetes | + | 381 | 17.1 | 1298 | 17.9 | 0.02 | 527 | 18.8 | 1074 | 18.5 | −0.01 |
| Smoking (within 1 year before surgery) | + | 539 | 24.2 | 1871 | 25.8 | 0.04 | 615 | 21.9 | 1369 | 23.5 | 0.04 |
| Habitual drinking | + | 728 | 32.7 | 2179 | 30 | −0.06 | 858 | 30.6 | 1682 | 28.9 | −0.04 |
| Dyspnea (within 30 days before surgery) | + | 22 | 1 | 86 | 1.2 | 0.02 | 37 | 1.3 | 80 | 1.4 | 0.00 |
| Activities of daily living (just before surgery) | Independence | 2183 | 98.1 | 7094 | 97.8 | −0.03 | 2713 | 96.8 | 5652 | 97.2 | 0.02 |
| Non‐independence | 42 | 1.9 | 162 | 2.2 | 0.03 | 90 | 3.2 | 164 | 2.8 | −0.02 | |
| Artificial respiration (48 h before surgery) | + | 1 | 0 | 5 | 0.1 | 0.01 | 1 | 0 | 3 | 0.1 | 0.01 |
| Chronic obstructive pulmonary disease | + | 91 | 4.1 | 344 | 4.7 | 0.03 | 161 | 5.7 | 272 | 4.7 | −0.05 |
| Pneumonia on admission | + | 9 | 0.4 | 26 | 0.4 | −0.01 | 9 | 0.3 | 29 | 0.5 | 0.03 |
| Ascites (within 30 days before surgery) | + | 90 | 4 | 340 | 4.7 | 0.03 | 84 | 3 | 197 | 3.4 | 0.02 |
| Hypertension (within 30 days before surgery) | + | 769 | 34.6 | 2438 | 33.6 | −0.02 | 1162 | 41.5 | 2176 | 37.4 | −0.08 |
| Congestive heart failure (within 30 days before surgery) | + | 5 | 0.2 | 17 | 0.2 | 0.00 | 13 | 0.5 | 27 | 0.5 | 0.00 |
| Myocardial infarction (within 6 months before surgery) | + | 11 | 0.5 | 15 | 0.2 | −0.04 | 12 | 0.4 | 19 | 0.3 | −0.02 |
| Angina pectoris (within 30 days before surgery) | + | 13 | 0.6 | 64 | 0.9 | 0.04 | 27 | 1 | 37 | 0.6 | −0.03 |
| Acute renal failure (within 24 h before surgery) | + | 1 | 0 | 2 | 0 | −0.01 | 0 | 0 | 0 | 0 | 0.00 |
| Hemodialysis (within 14 days before surgery) | + | 1 | 0 | 1 | 0 | −0.01 | 3 | 0.1 | 11 | 0.2 | 0.03 |
| Cerebrovascular disease | + | 77 | 3.5 | 240 | 3.3 | −0.01 | 136 | 4.9 | 197 | 3.4 | −0.07 |
| Advanced metastatic cancer (just before surgery) | + | 94 | 4.2 | 555 | 7.6 | 0.17 | 144 | 5.1 | 516 | 8.9 | 0.17 |
| Long‐term steroid use | + | 20 | 0.9 | 79 | 1.1 | 0.02 | 44 | 1.6 | 66 | 1.1 | −0.03 |
| Weight loss of ≥ 10% (within 6 months before surgery) | + | 203 | 9.1 | 918 | 12.7 | 0.12 | 201 | 7.2 | 658 | 11.3 | 0.16 |
| Bleeding risk factors (just before surgery) | + | 61 | 2.7 | 265 | 3.7 | 0.06 | 105 | 3.7 | 202 | 3.5 | −0.01 |
| Preoperative blood transfusion (72 h before surgery) | + | 39 | 1.8 | 248 | 3.4 | 0.13 | 73 | 2.6 | 244 | 4.2 | 0.10 |
| Sepsis (just before surgery) | + | 4 | 0.2 | 10 | 0.1 | −0.01 | 3 | 0.1 | 5 | 0.1 | −0.01 |
| American Society of Anesthesiologists—Physical Status | 1,2 | 1996 | 89.7 | 6444 | 88.8 | −0.03 | 2460 | 87.8 | 5049 | 86.8 | −0.03 |
| 3–5 | 229 | 10.3 | 812 | 11.2 | 0.03 | 343 | 12.2 | 767 | 13.2 | 0.03 | |
| Radiation therapy (within 90 days before surgery) | + | 27 | 1.2 | 92 | 1.3 | 0.00 | 111 | 4 | 71 | 1.2 | −0.14 |
| Immunotherapy (within 90 days before surgery) | + | 42 | 1.9 | 58 | 0.8 | −0.08 | 75 | 2.7 | 52 | 0.9 | −0.11 |
| cT | T0, Tis | 31 | 1.4 | 114 | 1.6 | 0.02 | 80 | 2.9 | 144 | 2.5 | −0.02 |
| T1 | 181 | 8.1 | 491 | 6.8 | −0.05 | 579 | 20.7 | 617 | 10.6 | −0.25 | |
| T2 | 185 | 8.3 | 506 | 7 | −0.05 | 362 | 12.9 | 669 | 11.5 | −0.04 | |
| T3 | 784 | 35.2 | 2272 | 31.3 | −0.08 | 890 | 31.8 | 1926 | 33.1 | 0.03 | |
| T4 | 1028 | 46.2 | 3811 | 52.5 | 0.13 | 866 | 30.9 | 2400 | 41.3 | 0.22 | |
| TX | 16 | 0.7 | 62 | 0.9 | 0.02 | 26 | 0.9 | 60 | 1 | 0.01 | |
| cN | N0 | 740 | 33.3 | 1838 | 25.3 | −0.17 | 1144 | 40.8 | 1588 | 27.3 | −0.27 |
| N1 | 461 | 20.7 | 1414 | 19.5 | −0.03 | 617 | 22 | 1225 | 21.1 | −0.02 | |
| N2 | 499 | 22.4 | 1715 | 23.6 | 0.03 | 593 | 21.2 | 1434 | 24.7 | 0.09 | |
| N3 | 502 | 22.6 | 2175 | 30 | 0.18 | 421 | 15 | 1442 | 24.8 | 0.27 | |
| NX | 23 | 1 | 114 | 1.6 | 0.05 | 28 | 1 | 127 | 2.2 | 0.12 | |
| cM | M0 | 1883 | 84.6 | 5488 | 75.6 | −0.25 | 2400 | 85.6 | 4441 | 76.4 | −0.26 |
| M1 | 342 | 15.4 | 1768 | 24.4 | 0.25 | 403 | 14.4 | 1375 | 23.6 | 0.26 | |
Abbreviations: MIS, minimally invasive surgery; SMD, standardized mean difference.
3.2. Surgical Outcomes
The surgical outcomes of the total and distal gastrectomies are shown in Table 2. In the total gastrectomy group, the minimally invasive surgery group had a lower rate of intraoperative blood transfusion (12.6% vs. 25.8%) and a higher rate of R0 resection (87.8% vs. 81.4%) than the open surgery group. The incidence of intraoperative events and the rate of readmission within 30 days postoperatively were similar in both groups. Furthermore, compared with the open surgery group, the minimally invasive surgery group had longer anesthesia (470 min vs. 356 min) and operation times (405 min vs. 297 min), lower blood loss (140 mL vs. 467.5 mL), and shorter postoperative hospital stay (13 days vs. 16 days). The amount of intraoperative fluid infusion was similar between groups.
TABLE 2.
Surgical outcomes.
| Factor | Category | Total gastrectomy | Distal gastrectomy | ||||||
|---|---|---|---|---|---|---|---|---|---|
| MIS (n = 2225) | Open (n = 7256) | MIS (n = 2803) | Open (n = 5816) | ||||||
| n | % | n | % | n | % | n | % | ||
| Intraoperative transfusion | + | 280 | 12.6 | 1873 | 25.8 | 228 | 8.1 | 1148 | 19.7 |
| Intraoperative events | + | 26 | 1.2 | 41 | 0.6 | 25 | 0.9 | 18 | 0.3 |
| Readmission within 30 days after surgery | + | 84 | 3.8 | 236 | 3.3 | 83 | 3 | 218 | 3.7 |
| R status | R0 | 1953 | 87.8 | 5907 | 81.4 | 2503 | 89.3 | 4810 | 82.7 |
| R1 | 145 | 6.5 | 643 | 8.9 | 106 | 3.8 | 345 | 5.9 | |
| R2 | 91 | 4.1 | 580 | 8 | 158 | 5.6 | 559 | 9.6 | |
| Rx | 36 | 1.6 | 126 | 1.7 | 36 | 1.3 | 102 | 1.8 | |
| Median | IQR | Median | IQR | Median | IQR | Median | IQR | |
|---|---|---|---|---|---|---|---|---|
| Anesthesia time (min) | 470 | [383, 567] | 356 | [293, 435] | 388 | [324, 465] | 318 | [259, 395] |
| Operation time (min) | 405 | [323, 494] | 297 | [238, 370] | 323 | [263, 397] | 263 | [205.75, 335] |
| Estimated blood loss (mL) | 140 | [40, 350] | 467.5 | [247, 825] | 50 | [10, 175] | 330 | [160, 610] |
| Intraoperative fluid volume (mL) | 2900 | [2200, 3800] | 2800 | [2100, 3700] | 2322 | [1800, 3100] | 2402.5 | [1800, 3251.75] |
| Length of stay (days) | 13 | [10, 19] | 16 | [12, 24] | 11 | [9, 15.5] | 14 | [11, 20] |
Abbreviations: IQR, interquartile range; MIS, minimally invasive surgery; R, Residual tumor status.
In the distal gastrectomy group, the minimally invasive surgery group had a lower rate of intraoperative blood transfusion than the open surgery group (8.1% vs. 19.7%) and a higher rate of R0 resection (89.3% vs. 82.7%). The incidence of intraoperative events and the rate of readmission within 30 days after surgery were similar in both groups. Furthermore, compared with the open surgery group, the minimally invasive surgery group had longer anesthesia time (388 min vs. 318 min) and operative time (323 min vs. 263 min), less blood loss (50 mL vs. 330 mL), and shorter postoperative hospital stay (11 days vs. 14 days). The amount of intraoperative fluid infusion was similar between groups.
3.2.1. Postoperative Complications
Postoperative complications before IPTW for total and distal gastrectomies are listed in Table 3. For total gastrectomy, the overall incidences of grade ≥ 1 (29.3% vs. 32.8%), grade ≥ 2 (23.4% vs. 24.8%), and grade ≥ 3 (9.2% vs. 10.5%) postoperative complications were slightly lower in the minimally invasive surgery group than in the open surgery group. Regarding individual complications, the incidences of superficial incisional surgical site infection (SSI) and pancreatic fistulas were slightly lower in the minimally invasive surgery group, whereas the incidences of other complications were similar in both groups. The proportion of patients who received blood transfusions was higher in the open surgery group.
TABLE 3.
Postoperative complications.
| Total gastrectomy | Distal gastrectomy | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| MIS (n = 2225) | Open (n = 7256) | MIS (n = 2803) | Open (n = 5816) | ||||||
| n | % | n | % | n | % | n | % | ||
| Overall complication (Clavien‐Dindo classification) | Grade 0 | 1573 | 70.7 | 4875 | 67.2 | 2155 | 76.9 | 4078 | 70.1 |
| Grade I | 132 | 5.9 | 581 | 8 | 175 | 6.2 | 546 | 9.4 | |
| Grade II | 315 | 14.2 | 1042 | 14.4 | 300 | 10.7 | 766 | 13.2 | |
| Grade III | 180 | 8.1 | 679 | 9.4 | 146 | 5.2 | 368 | 6.3 | |
| Grade IV | 14 | 0.6 | 46 | 0.6 | 16 | 0.6 | 34 | 0.6 | |
| Grade V | 11 | 0.5 | 33 | 0.5 | 11 | 0.4 | 24 | 0.4 | |
| Individual complications | |||||||||
| Superficial incisional surgical site infection | + | 41 | 1.8 | 202 | 2.8 | 45 | 1.6 | 188 | 3.2 |
| Deep incisional surgical site infection | + | 17 | 0.8 | 95 | 1.3 | 12 | 0.4 | 55 | 0.9 |
| Organ/space surgical site infection | + | 112 | 5 | 402 | 5.5 | 99 | 3.5 | 198 | 3.4 |
| Wound dehiscence with fascial disruption | + | 9 | 0.4 | 37 | 0.5 | 8 | 0.3 | 33 | 0.6 |
| Anastomotic leakage | + | 100 | 4.5 | 316 | 4.4 | 76 | 2.7 | 136 | 2.3 |
| Pancreatic fistula | + | 69 | 3.1 | 333 | 4.6 | 50 | 1.8 | 165 | 2.8 |
| Delayed gastric emptying | + | 16 | 0.7 | 56 | 0.8 | 58 | 2.1 | 139 | 2.4 |
| Bile fistula | + | 6 | 0.3 | 41 | 0.6 | 9 | 0.3 | 37 | 0.6 |
| Pneumonia | + | 79 | 3.6 | 273 | 3.8 | 61 | 2.2 | 145 | 2.5 |
| Unplanned endotracheal intubation | + | 27 | 1.2 | 82 | 1.1 | 17 | 0.6 | 40 | 0.7 |
| Pulmonary embolism | + | 8 | 0.4 | 15 | 0.2 | 0 | 0 | 8 | 0.1 |
| Mechanically ventilated (≥ 48 h) | + | 25 | 1.1 | 82 | 1.1 | 14 | 0.5 | 36 | 0.6 |
| Renal dysfunction | + | 15 | 0.7 | 60 | 0.8 | 15 | 0.5 | 38 | 0.7 |
| Urinary tract infection | + | 15 | 0.7 | 46 | 0.6 | 8 | 0.3 | 32 | 0.6 |
| Central nervous system disorder | + | 4 | 0.2 | 11 | 0.2 | 5 | 0.2 | 11 | 0.2 |
| Cardiac arrest | + | 6 | 0.3 | 16 | 0.2 | 5 | 0.2 | 9 | 0.2 |
| Myocardial infarction | + | 0 | 0 | 1 | 0 | 1 | 0 | 3 | 0.1 |
| Blood transfusion | + | 91 | 4.1 | 421 | 5.8 | 74 | 2.6 | 280 | 4.8 |
| Deep venous thrombosis | + | 16 | 0.7 | 46 | 0.6 | 8 | 0.3 | 34 | 0.6 |
| Sepsis | + | 26 | 1.2 | 126 | 1.7 | 25 | 0.9 | 79 | 1.4 |
| Reoperation within 30 days after surgery | + | 67 | 3 | 229 | 3.2 | 76 | 2.7 | 163 | 2.8 |
| Death within 30 days after surgery | + | 12 | 0.5 | 44 | 0.6 | 11 | 0.4 | 28 | 0.5 |
Abbreviation: MIS, minimally invasive surgery.
For distal gastrectomy, the overall postoperative complication rates of grade ≥ 1 (23.1% vs. 29.9%), grade ≥ 2 (16.9% vs. 20.5%), and grade ≥ 3 (6.2% vs. 7.3%) were slightly lower in the minimally invasive surgery group than in the open surgery group. Regarding individual complications, the incidences of superficial incisional SSI and pancreatic fistulas were slightly lower in the minimally invasive surgery group; however, the rates of other complications were similar in both groups. The proportion of patients who received blood transfusions was higher in the open surgery group.
3.2.2. Patient Characteristics After IPTW
To ensure the validity of the comparison between minimally invasive and open surgeries regarding the incidence rate of complications set as evaluation items in this study, an adjustment was performed using IPTW. For both total and distal gastrectomies, all background variables showed an absolute SMD of < 0.1 between the minimally invasive and open surgery groups, indicating that the balance between the two groups was sufficiently adjusted (Table 4).
TABLE 4.
Patient characteristics after IPTW.
| Factor | Category | Total gastrectomy | Distal gastrectomy | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| MIS (n = 2225) | Open (n = 2224.1) | SMD | MIS (n = 2803) | Open (n = 2800.9) | SMD | ||||||
| n | % | n | % | n | % | n | % | ||||
| Age (years) | < 70 | 1176 | 52.9 | 1177.2 | 52.9 | 0.00 | 1219 | 43.5 | 1204.1 | 43 | −0.01 |
| ≥ 70 | 1049 | 47.1 | 1046.9 | 47.1 | 0.00 | 1584 | 56.5 | 1596.8 | 57 | 0.01 | |
| Sex | Male | 1554 | 69.8 | 1556.3 | 70 | 0.00 | 1961 | 70 | 1966.3 | 70.2 | 0.01 |
| Female | 671 | 30.2 | 667.9 | 30 | 0.00 | 842 | 30 | 834.6 | 29.8 | −0.01 | |
| Body mass index | < 18.5 | 376 | 16.9 | 379 | 17 | 0.00 | 430 | 15.3 | 425.1 | 15.2 | 0.00 |
| 18.5 ≤, < 25 | 1501 | 67.5 | 1496.9 | 67.3 | 0.00 | 1928 | 68.8 | 1928 | 68.8 | 0.00 | |
| ≥ 25 | 348 | 15.6 | 348.2 | 15.7 | 0.00 | 445 | 15.9 | 447.8 | 16 | 0.00 | |
| Diabetes | + | 381 | 17.1 | 377.3 | 17 | 0.00 | 527 | 18.8 | 539.8 | 19.3 | 0.01 |
| Smoking (within 1 year before surgery) | + | 539 | 24.2 | 538.2 | 24.2 | 0.00 | 615 | 21.9 | 615.9 | 22 | 0.00 |
| Habitual drinking | + | 728 | 32.7 | 726.8 | 32.7 | 0.00 | 858 | 30.6 | 852.4 | 30.4 | 0.00 |
| Dyspnea (within 30 days before surgery) | + | 22 | 1 | 21.4 | 1 | 0.00 | 37 | 1.3 | 38.4 | 1.4 | 0.00 |
| Activities of daily living (just before surgery) | Independence | 2183 | 98.1 | 2181.6 | 98.1 | 0.00 | 2713 | 96.8 | 2708 | 96.7 | −0.01 |
| Non‐independence | 42 | 1.9 | 42.5 | 1.9 | 0.00 | 90 | 3.2 | 92.8 | 3.3 | 0.01 | |
| Artificial respiration (48 h before surgery) | + | 1 | 0 | 0.9 | 0 | 0.00 | 1 | 0 | 0.7 | 0 | −0.01 |
| Chronic obstructive pulmonary disease | + | 91 | 4.1 | 91.8 | 4.1 | 0.00 | 161 | 5.7 | 154.1 | 5.5 | −0.01 |
| Pneumonia on admission | + | 9 | 0.4 | 9.1 | 0.4 | 0.00 | 9 | 0.3 | 9.3 | 0.3 | 0.00 |
| Ascites (within 30 days before surgery) | + | 90 | 4 | 90.8 | 4.1 | 0.00 | 84 | 3 | 87.4 | 3.1 | 0.01 |
| Hypertension (within 30 days before surgery) | + | 769 | 34.6 | 768 | 34.5 | 0.00 | 1162 | 41.5 | 1166.9 | 41.7 | 0.00 |
| Congestive heart failure (within 30 days before surgery) | + | 5 | 0.2 | 5.3 | 0.2 | 0.00 | 13 | 0.5 | 15.2 | 0.5 | 0.01 |
| Myocardial infarction (within 6 months before surgery) | + | 11 | 0.5 | 10.6 | 0.5 | 0.00 | 12 | 0.4 | 10.9 | 0.4 | −0.01 |
| Angina pectoris (within 30 days before surgery) | + | 13 | 0.6 | 14.2 | 0.6 | 0.01 | 27 | 1 | 28.2 | 1 | 0.00 |
| Acute renal failure (within 24 h before surgery)* | + | 1 | 0 | 0.8 | 0 | 0.00 | 0 | 0 | 0 | 0 | 0.00 |
| Hemodialysis (within 14 days before surgery) | + | 1 | 0 | 1 | 0 | 0.00 | 3 | 0.1 | 5.9 | 0.2 | 0.03 |
| Cerebrovascular disease | + | 77 | 3.5 | 76.7 | 3.4 | 0.00 | 136 | 4.9 | 137.1 | 4.9 | 0.00 |
| Advanced metastatic cancer (just before surgery) | + | 94 | 4.2 | 92.6 | 4.2 | 0.00 | 144 | 5.1 | 140.5 | 5 | −0.01 |
| Long‐term steroid use | + | 20 | 0.9 | 19.9 | 0.9 | 0.00 | 44 | 1.6 | 46.2 | 1.7 | 0.01 |
| Weight loss of ≥ 10% (within 6 months before surgery) | + | 203 | 9.1 | 200.7 | 9 | 0.00 | 201 | 7.2 | 198.6 | 7.1 | 0.00 |
| Bleeding risk factors (just before surgery) | + | 61 | 2.7 | 60.5 | 2.7 | 0.00 | 105 | 3.7 | 108.8 | 3.9 | 0.01 |
| Preoperative blood transfusion (72 h before surgery) | + | 39 | 1.8 | 40.3 | 1.8 | 0.00 | 73 | 2.6 | 74.2 | 2.7 | 0.00 |
| Sepsis (just before surgery) | + | 4 | 0.2 | 3.3 | 0.1 | −0.01 | 3 | 0.1 | 3.1 | 0.1 | 0.00 |
| American Society of Anesthesiologists—Physical status | 1,2 | 1996 | 89.7 | 1994.9 | 89.7 | 0.00 | 2460 | 87.8 | 2454 | 87.6 | 0.00 |
| 3–5 | 229 | 10.3 | 229.3 | 10.3 | 0.00 | 343 | 12.2 | 346.9 | 12.4 | 0.00 | |
| Radiation therapy (within 90 days before surgery) | + | 27 | 1.2 | 28.9 | 1.3 | 0.01 | 111 | 4 | 109.6 | 3.9 | 0.00 |
| Immunotherapy (within 90 days before surgery) | + | 42 | 1.9 | 41.3 | 1.9 | 0.00 | 75 | 2.7 | 91 | 3.2 | 0.04 |
| cT | T0, Tis | 31 | 1.4 | 31.3 | 1.4 | 0.00 | 80 | 2.9 | 79.7 | 2.8 | 0.00 |
| T1 | 181 | 8.1 | 180.5 | 8.1 | 0.00 | 579 | 20.7 | 555 | 19.8 | −0.02 | |
| T2 | 185 | 8.3 | 185 | 8.3 | 0.00 | 362 | 12.9 | 361.3 | 12.9 | 0.00 | |
| T3 | 784 | 35.2 | 787.4 | 35.4 | 0.00 | 890 | 31.8 | 902.3 | 32.2 | 0.01 | |
| T4 | 1028 | 46.2 | 1023.5 | 46 | 0.00 | 866 | 30.9 | 876.1 | 31.3 | 0.01 | |
| TX | 16 | 0.7 | 16.5 | 0.7 | 0.00 | 26 | 0.9 | 26.4 | 0.9 | 0.00 | |
| cN | N0 | 740 | 33.3 | 741.7 | 33.3 | 0.00 | 1144 | 40.8 | 1124.5 | 40.1 | −0.01 |
| N1 | 461 | 20.7 | 460.5 | 20.7 | 0.00 | 617 | 22 | 626.5 | 22.4 | 0.01 | |
| N2 | 499 | 22.4 | 499.3 | 22.4 | 0.00 | 593 | 21.2 | 600.1 | 21.4 | 0.01 | |
| N3 | 502 | 22.6 | 499.7 | 22.5 | 0.00 | 421 | 15 | 421.1 | 15 | 0.00 | |
| NX | 23 | 1 | 22.9 | 1 | 0.00 | 28 | 1 | 28.7 | 1 | 0.00 | |
| cM | M0 | 1883 | 84.6 | 1882.5 | 84.6 | 0.00 | 2400 | 85.6 | 2395.2 | 85.5 | 0.00 |
| M1 | 342 | 15.4 | 341.6 | 15.4 | 0.00 | 403 | 14.4 | 405.7 | 14.5 | 0.00 | |
Abbreviations: IPTW, Inverse probability of treatment weighting; MIS, minimally invasive surgery.
Acute renal failure was excluded from the propensity score model for DG because only one category was observed.
3.2.3. Postoperative Complications After IPTW
Postoperative complications after IPTW for total and distal gastrectomies are listed in Table 5. In total gastrectomy, the primary outcome, overall complications of grade ≥ 1, was significantly lower in the minimally invasive surgery group than in the open surgery group (29.3% vs. 32.1%, RR: 0.91, 95% CI: 0.85–0.98). There was no significant difference between the two groups in terms of overall complications of grade ≥ 2 (23.4% vs. 24.4%, RR: 0.96, 95% CI: 0.88–1.04) and grade ≥ 3 (9.2% vs. 10.3%, RR: 0.90, 95% CI: 0.77–1.04). For individual complications, superficial incisional SSI (1.8% vs. 2.6%, RR: 0.70, 95% CI: 0.50–0.98), deep incisional SSI (0.8% vs. 1.3%, RR: 0.59, 95% CI: 0.36–0.99), and pancreatic fistula (3.1% vs. 4.6%, RR: 0.67, 95% CI: 0.52–0.86) were all significantly lower with minimally invasive surgery. No significant differences were observed between the groups in terms of other complications. The proportion of patients who received blood transfusions was significantly lower in the minimally invasive surgery group (4.1% vs. 5.2%; RR: 0.78; 95% CI: 0.63–0.98).
TABLE 5.
Postoperative complications after IPTW.
| Total gastrectomy* | Distal gastrectomy** | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIS (%) | Open (%) | RD (%) | 95% CI (%) | p | RR | 95% CI | p | MIS (%) | Open (%) | RD (%) | 95% CI (%) | p | RR | 95% CI | p | |
| Overall complications (CD grade ≥ 1) | 29.3 | 32.1 | −2.8 | (−5.0, −0.6) | 0.011 | 0.91 | (0.85, 0.98) | 0.013 | 23.1 | 29.7 | −6.6 | (−8.6, −4.6) | < 0.001 | 0.78 | (0.72, 0.84) | < 0.001 |
| Overall complications (CD grade ≥ 2) | 23.4 | 24.4 | −1.0 | (−3.0, 1.0) | 0.320 | 0.96 | (0.88, 1.04) | 0.325 | 16.9 | 20.1 | −3.2 | (−5.0, −1.4) | < 0.001 | 0.84 | (0.76, 0.93) | < 0.001 |
| Overall complications (CD grade ≥ 3) | 9.2 | 10.3 | −1.1 | (−2.5, 0.3) | 0.137 | 0.90 | (0.77, 1.04) | 0.148 | 6.2 | 7.0 | −0.8 | (−2.0, 0.3) | 0.161 | 0.88 | (0.74, 1.05) | 0.168 |
| Individual complications | ||||||||||||||||
| Superficial incisional surgical site infection | 1.8 | 2.6 | −0.8 | (−1.5, −0.1) | 0.023 | 0.7 | (0.50, 0.98) | 0.038 | 1.6 | 3.2 | −1.6 | (−2.3, −0.9) | < 0.001 | 0.51 | (0.36, 0.70) | < 0.001 |
| Deep incisional surgical site infection a , b | 0.8 | 1.3 | −0.5 | (−1.0, −0.1) | 0.021 | 0.59 | (0.36, 0.99) | 0.045 | 0.4 | 0.9 | −0.5 | (−0.9, −0.1) | 0.009 | 0.47 | (0.25, 0.88) | 0.019 |
| Organ/space surgical site infection | 5.0 | 5.3 | −0.3 | (−1.4, 0.7) | 0.557 | 0.94 | (0.76, 1.16) | 0.574 | 3.5 | 3.3 | 0.2 | (−0.6, 1.1) | 0.565 | 1.08 | (0.84, 1.37) | 0.562 |
| Wound dehiscence with fascial disruption a , b | 0.4 | 0.5 | −0.1 | (−0.4, 0.2) | 0.649 | 0.85 | (0.40, 1.79) | 0.662 | 0.3 | 0.5 | −0.3 | (−0.5, 0.0) | 0.062 | 0.52 | (0.24, 1.12) | 0.096 |
| Anastomotic leakage a , b | 4.5 | 4.4 | 0.1 | (−0.9, 1.1) | 0.831 | 1.02 | (0.82, 1.28) | 0.83 | 2.7 | 2.1 | 0.6 | (−0.2, 1.3) | 0.122 | 1.27 | (0.95, 1.69) | 0.112 |
| Pancreatic fistula b | 3.1 | 4.6 | −1.5 | (−2.4, −0.7) | < 0.001 | 0.67 | (0.52, 0.86) | 0.002 | 1.8 | 2.5 | −0.7 | (−1.4, −0.1) | 0.026 | 0.71 | (0.51, 0.98) | 0.036 |
| Delayed gastric emptying a , b | 0.7 | 0.8 | 0.0 | (−0.4, 0.4) | 0.876 | 0.96 | (0.54, 1.69) | 0.877 | 2.1 | 2.5 | −0.5 | (−1.2, 0.3) | 0.206 | 0.82 | (0.59, 1.12) | 0.214 |
| Bile fistula b | 0.3 | 0.5 | −0.3 | (−0.5, 0.0) | 0.065 | 0.51 | (0.22, 1.19) | 0.12 | 0.3 | 0.6 | −0.3 | (−0.6, 0.0) | 0.053 | 0.52 | (0.25, 1.09) | 0.084 |
| Pneumonia | 3.6 | 3.7 | −0.1 | (−1.0, 0.7) | 0.763 | 0.96 | (0.75, 1.23) | 0.765 | 2.2 | 2.4 | −0.2 | (−0.9, 0.5) | 0.566 | 0.92 | (0.68, 1.24) | 0.571 |
| Unplanned endotracheal intubation a , b | 1.2 | 1.1 | 0.1 | (−0.4, 0.7) | 0.587 | 1.13 | (0.73, 1.76) | 0.577 | 0.6 | 0.6 | 0.0 | (−0.4, 0.3) | 0.933 | 0.98 | (0.55, 1.72) | 0.934 |
| Pulmonary embolism a | 0.4 | 0.2 | 0.2 | (−0.1, 0.4) | 0.236 | 1.86 | (0.74, 4.69) | 0.186 | Not applicable | |||||||
| Mechanically ventilated (≥ 48 h) a , b | 1.1 | 1.0 | 0.1 | (−0.4, 0.6) | 0.769 | 1.07 | (0.68, 1.69) | 0.766 | 0.5 | 0.6 | −0.1 | (−0.4, 0.2) | 0.574 | 0.84 | (0.46, 1.55) | 0.584 |
| Renal dysfunction a , b | 0.7 | 0.8 | −0.1 | (−0.5, 0.3) | 0.697 | 0.9 | (0.51, 1.58) | 0.704 | 0.5 | 0.6 | 0.0 | (−0.4, 0.3) | 0.864 | 0.95 | (0.52, 1.74) | 0.864 |
| Urinary tract infection a , b | 0.7 | 0.6 | 0.1 | (−0.3, 0.5) | 0.759 | 1.1 | (0.60, 2.03) | 0.754 | 0.3 | 0.6 | −0.3 | (−0.7, 0.1) | 0.133 | 0.50 | (0.20, 1.23) | 0.132 |
| Central nervous system disorder b | Not applicable | 0.2 | 0.2 | 0.0 | (−0.2, 0.2) | 0.692 | 0.82 | (0.31, 2.22) | 0.701 | |||||||
| Cardiac arrest a | 0.3 | 0.2 | 0.1 | (−0.1, 0.3) | 0.459 | 1.49 | (0.57, 3.93) | 0.416 | Not applicable | |||||||
| Blood transfusion a | 4.1 | 5.2 | −1.1 | (−2.1, −0.2) | 0.022 | 0.78 | (0.63, 0.98) | 0.032 | 2.6 | 4.3 | −1.7 | (−2.5, −0.9) | < 0.001 | 0.61 | (0.47, 0.79) | < 0.001 |
| Deep venous thrombosis a , b | 0.7 | 0.6 | 0.1 | (−0.3, 0.5) | 0.646 | 1.15 | (0.64, 2.06) | 0.636 | 0.3 | 0.7 | −0.4 | (−0.7, −0.1) | 0.020 | 0.43 | (0.20, 0.94) | 0.033 |
| Sepsis a , b | 1.2 | 1.5 | −0.3 | (−0.8, 0.2) | 0.264 | 0.8 | (0.52, 1.22) | 0.294 | 0.9 | 1.1 | −0.2 | (−0.7, 0.2) | 0.341 | 0.80 | (0.50, 1.28) | 0.358 |
| Reoperation within 30 days after surgery b | 3.0 | 3.1 | −0.1 | (−0.9, 0.7) | 0.781 | 0.96 | (0.74, 1.26) | 0.783 | 2.7 | 2.7 | 0.0 | (−0.8, 0.8) | 0.994 | 1.00 | (0.75, 1.32) | 0.994 |
| Death within 30 days after surgery a , b | 0.5 | 0.5 | 0.1 | (−0.3, 0.4) | 0.647 | 1.18 | (0.60, 2.30) | 0.635 | 0.4 | 0.3 | 0.1 | (−0.2, 0.4) | 0.503 | 1.34 | (0.59, 3.05) | 0.489 |
Note: Treatment‐specific risks are shown as reference values because treatment–covariate interaction terms were omitted from the outcome model due to sparse data/instability.
Abbreviations: CI, confidence interval; IPTW, Inverse probability of treatment weighting; MIS, minimally invasive surgery; RD, risk difference; RR, risk ratio.
Estimates for central nervous system disorder and myocardial infarction were not reported due to model non‐convergence caused by very low event counts.
Estimates for pulmonary embolism, cardiac arrest, and myocardial infarction were not reported due to model non‐convergence caused by very low event counts.
Outcomes applicable to total gastrectomy.
Outcomes applicable to distal gastrectomy.
In distal gastrectomy, both the primary outcome, overall complications of grade ≥ 1 (23.1% vs. 29.7%, RR: 0.78, 95% CI: 0.72–0.84), and overall complications of grade ≥ 2 (16.9% vs. 20.1%, RR: 0.84, 95% CI: 0.76–0.93) were significantly lower in the minimally invasive surgery group than in the open surgery group. There was no significant difference between the two groups in terms of overall complications of grade ≥ 3 (6.2% vs. 7.0%, RR: 0.88, 95% CI: 0.74–1.05). Regarding individual complications, superficial incisional SSI (1.6% vs. 3.2%, RR: 0.51, 95% CI: 0.36–0.70), deep incisional SSI (0.4% vs. 0.9%, RR: 0.47, 95% CI: 0.25–0.88), pancreatic fistula (1.8% vs. 2.5%, RR: 0.71, 95% CI: 0.51–0.98), and deep venous thrombosis (0.3% vs. 0.7%, RR: 0.43, 95% CI: 0.20–0.94) were all significantly lower in the minimally invasive surgery group. There were no significant differences in other complications between the two groups. The blood transfusion rate was significantly lower in the minimally invasive surgery group (2.6% vs. 4.3%; RR, 0.61; 95% CI: 0.47–0.79).
4. Discussion
This study examined minimally invasive and open surgeries in patients who underwent total or distal gastrectomy after chemotherapy, using nationwide data from Japan. Subsequently, postoperative complications were compared between the minimally invasive and open surgeries using propensity scores. In patients who underwent minimally invasive surgery, both total and distal gastrectomies had longer operative times, less blood loss, and shorter hospital stays than open surgery. Regarding postoperative complications, the overall complication rate and many individual complication rates were lower with minimally invasive surgery. In comparative studies using propensity scores, the incidence of overall postoperative complications was lower with minimally invasive surgery, and incidences of superficial incisional SSI, deep incisional SSI, and pancreatic fistulas were also lower.
Several randomized controlled trials, including the KLASS‐01, KLASS‐02, JCOG0912, and CLASS‐02 trials, have demonstrated that minimally invasive surgery provides short‐term outcomes comparable or superior to those of open gastrectomy, particularly with respect to overall postoperative morbidity and wound‐related complications [12, 13, 14, 15, 16]. However, the effect of minimally invasive surgery on pancreatic fistula remains controversial. With recent advancements in endoscopic technology, it has become possible to perform laparoscopic surgery using a 3D visual field, and the outcomes of laparoscopic surgery for gastric cancer have continued to facilitate [17, 18]. Furthermore, as robotic surgery becomes more widespread, stable visualization and prevention of hand tremors during fine maneuvers have facilitated, likely enhancing the precision of dissection techniques [19]. According to an analysis based on the NCD by Hiki et al., the incidence of Grade B or higher pancreatic fistulas was 2.2% after laparoscopic surgery and 1.0% after open surgery, with a significantly higher incidence of pancreatic leakage in the laparoscopic group [20]. In contrast, Fujiya et al. examined the risk factors for pancreatic fistulas; however, the surgical approach was not identified as a significant factor [21]. In a recent RCT, the LOGICA trial, no difference was found between laparoscopic and open surgeries for pancreatic leakage [22]. Results from meta‐analyses include reports that the incidence of pancreatic fistulas is higher with laparoscopic surgery, and others that it is similar to open surgery [23, 24]. Several studies have reported that robotic surgery for gastric cancer was associated with a lower incidence of postoperative complications compared with open surgery; however, no studies have reported that robotic surgery was associated with the lower incidence of pancreatic fistulas [25, 26]. There is no consensus on whether minimally invasive or open surgery is superior for preventing postoperative pancreatic fistulas in patients with gastric cancer.
In this study, minimally invasive (laparoscopic/robotic) surgery was associated with a lower incidence of pancreatic fistulas than open surgery in patients with gastric cancer who underwent gastrectomy after preoperative chemotherapy. This finding differs from that of a previous NCD‐based analysis that reported a higher incidence of pancreatic fistulas after laparoscopic gastrectomy. Because robotic surgery for gastric cancer was approved for insurance coverage in Japan in April 2018, it was assumed that the majority of minimally invasive surgeries in this study were laparoscopic. Several factors may have accounted for this discrepancy. First, in gastric cancer surgery following chemotherapy, tissue fibrosis occurs, making it difficult to identify the dissection planes around the pancreas and blood vessels [8, 9]. A precise anatomical understanding, enabled by minimally invasive surgery, may help reduce pancreatic fistulas. Second, this study spanned recent years, and temporal advancements in surgical techniques and perioperative management, including case concentration in experienced centers, may also have contributed to the lower fistula rates in the laparoscopic group. Third, surgery for gastric cancer after chemotherapy is highly challenging and is often performed by expert surgeons [20].
Evidence, specifically in postchemotherapy settings, is limited. An RCT of distal gastrectomy after NAC reported pancreatic fistula rates of 0% after laparoscopic surgery and 2% after open surgery, without a significant difference [27]. To our knowledge, no other studies have reported a significant difference in the incidence of pancreatic fistulas between laparoscopic and open surgery after NAC [28, 29]. The incidence of pancreatic fistulas was 2.4% in minimally invasive surgery and 1.9% in open surgery, with no significant difference observed between the two groups in conversion surgery [30]. A plausible explanation for these null findings is the relatively small sample size and low frequency of pancreatic fistulas, which may limit the statistical power. In contrast, our large nationwide cohort enabled the detection of a statistically significant but modest absolute reduction in the incidence of pancreatic fistulas (1.5% in total gastrectomy and 0.7% in distal gastrectomy), and its clinical significance should therefore be interpreted cautiously. Nevertheless, clinically relevant postoperative pancreatic fistula remains one of the most important complications after gastrectomy because it may lead to severe secondary complications, prolonged hospitalization, and increased healthcare utilization.
The strength of this study lies in the use of complete data on total and distal gastrectomies for gastric cancer in Japan. This descriptive investigation provides a comprehensive overview of current treatment outcomes in Japan. Furthermore, with respect to postoperative complications, patient backgrounds were adjusted using propensity scores to ensure the validity of the comparisons. Consistent with previous reports, this study demonstrated that minimally invasive surgery was associated with lower incidences of overall postoperative and incision‐related complications. Additionally, it revealed that minimally invasive surgery was associated with a lower incidence of pancreatic fistulas following gastric cancer surgery after chemotherapy, a finding that remains unclear. However, this study had some limitations. Laparoscopic and robotic procedures were analyzed together as minimally invasive surgery, and their individual associations with postoperative outcomes could not be evaluated. Patients who underwent conversion to open surgery were included in the minimally invasive surgery group. Because these patients were not analyzed separately, the potential impact of conversion to open surgery on the observed association between surgical approach and postoperative outcomes could not be fully evaluated. Also, complete‐case analysis was performed after exclusion of patients with missing values. Therefore, selection bias may have been introduced if the missingness was not completely random, and the findings should be interpreted with this limitation in mind. Moreover, the study period spanned nearly a decade, during which substantial advances occurred in laparoscopic surgery, robotic surgery, perioperative management, and pancreatic fistula prevention techniques. In addition, the adoption of minimally invasive surgery increased over time in Japan and may have been concentrated in high‐volume institutions and among experienced surgeons. Therefore, part of the observed association between minimally invasive surgery and improved postoperative outcomes may reflect temporal advancements in surgical practice and institutional expertise rather than the surgical approach itself. In addition, because minimally invasive surgery was performed primarily at high‐volume centers, differences among institutions may have influenced the findings of this study. An important limitation of the present study is that neoadjuvant chemotherapy and conversion surgery could not be distinguished within the NCD dataset. These populations differ substantially in disease biology, operative complexity, and postoperative risk. In particular, conversion surgery is often performed for initially unresectable or metastatic disease and may involve greater technical difficulty than planned surgery after neoadjuvant chemotherapy. In addition, the higher proportion of cM1 disease in the open surgery group suggests that more advanced cases may have been preferentially treated with open surgery. Therefore, heterogeneity within the study population may have influenced the observed associations. The higher R0 resection rate observed in the minimally invasive surgery group may also reflect differences in patient selection. Despite extensive adjustment using IPTW, residual confounding may remain because patients with more advanced disease and greater operative complexity may have been preferentially selected for open surgery. Therefore, the observed association between minimally invasive surgery and improved postoperative outcomes should not be interpreted as evidence of a direct causal effect of the surgical approach itself. Although minimally invasive surgery was associated with a lower incidence of overall complications of CD grade ≥ 1, differences in more severe complications were less pronounced. Therefore, the clinical significance of the observed reduction in overall morbidity should be interpreted cautiously. This consideration may be particularly relevant in total gastrectomy, where no statistically significant difference was observed for complications of CD grade ≥ 2 and grade ≥ 3.
5. Conclusions
In patients with gastric cancer who underwent total or distal gastrectomy after chemotherapy, including NAC and conversion surgery, minimally invasive surgery was associated with lower rates of postoperative complications (CD grade ≥ 1), particularly wound‐related complications and pancreatic fistulas, compared to open surgery. However, differences in more severe complications were less pronounced and should be interpreted cautiously.
Author Contributions
Nobuaki Hoshino: conceptualization, methodology, writing – original draft, investigation. Shinya Hirakawa: methodology, data curation, writing – review and editing, formal analysis. Shiogeo Hisamori: conceptualization, methodology, investigation, writing – review and editing. Hisateru Tachimori: methodology, formal analysis, writing – review and editing. Yusuke Fujii: conceptualization, writing – review and editing, methodology. Koshi Kumagai: writing – review and editing, supervision. Hideki Ueno: supervision, writing – review and editing, project administration. Ken Shirabe: writing – review and editing, supervision, project administration. Kazutaka Obama: project administration, supervision, writing – review and editing.
Funding
The authors have nothing to report.
Ethics Statement
The protocol for this research project has been approved by the Ethics Committee of Kyoto University (Approval No. R4101).
Conflicts of Interest
Ken Shirabe is Editor‐in‐Chief of Annals of Gastroenterological Surgery. Hideki Ueno is Chief Associate Editor of Annals of Gastroenterological Surgery. Shinya Hirakawa and Hisateru Tachimori were affiliated with the Endowed Course for Health System Innovation at Keio University, funded by Takeda Pharmaceutical Company Limited, until March 31, 2024. Shinya Hirakawa and Hisateru Tachimori are affiliated with the Department, which receives grants from the National Clinical Database, Johnson & Johnson K.K., Nipro Corporation, and Intuitive Surgical Sàrl, and AstraZeneca K.K.
Supporting information
Table S1: Number of missing values per variable.
Table S2: Annual trends in the numbers of open and minimally invasive surgeries.
Table S3: Annual trends in the numbers of laparoscopic and robotic surgeries.
Data Availability Statement
The data that support the findings of this study are available from The Japanese Society of Gastroenterological Surgery. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the author(s) with the permission of The Japanese Society of Gastroenterological Surgery.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1: Number of missing values per variable.
Table S2: Annual trends in the numbers of open and minimally invasive surgeries.
Table S3: Annual trends in the numbers of laparoscopic and robotic surgeries.
Data Availability Statement
The data that support the findings of this study are available from The Japanese Society of Gastroenterological Surgery. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the author(s) with the permission of The Japanese Society of Gastroenterological Surgery.