Billroth-I anastomosis in distal subtotal gastrectomy for non-early gastric adenocarcinoma

Outcomes of distal subtotal gastrectomy for NEGA were compared between the patients who had received B-I anastomosis and those who had received B-II anastomosis. The primary endpoints of this study were long-term oncologic outcomes, namely, recurrence and survival. Secondary endpoints intra- and postoperative outcomes.

Patient demographics, clinical presentation and perioperative parameters were prospectively registered in the database throughout the study period. The long-term oncologic data were obtained from outpatient hospital visits and telephone interviews. Propensity score matching (PSM) was applied to minimize selection bias. Propensity scores were based on age, gender, tumor location, tumor size, type of resection, tumor stage and nodal stage as we believe most of these factors may influence the choice of anastomosis technique. Patients with either of these variables missing were excluded from the matching procedure.

The study protocol was considered by the accredited Institutional Review Board for Medical Ethics. The requirement for approval was waived by the ethics committee due to the retrospective nature of this study.

All patients who had undergone distal subtotal gastrectomy for NEGA within the study period met the inclusion criteria for this study. NEGA was defined as stage IB-IIIC gastric adenocarcinoma confirmed on final pathology. Patients with NEGA who had undergone surgical procedures other than distal subtotal gastrectomy, were excluded from the analysis. So were those with distant metastases or with gastric tumors other than adenocarcinoma.

Extended gastrectomy was defined as en-bloc resection of adjacent organs and structures due to clinically verified tumor invasion (cT4b stage gastric cancer) as described elsewhere.⁷ Morbidity was defined according to Clavien and Dindo.⁸ Grade ≥ IIIa complications were considered severe.

The 8^th edition of American Joint Committee on Cancer (AJCC) staging manual for gastric cancer was used for TNM classification and disease staging.⁹ Tumor size was determined by its morphometric measurement at the pathology work-up. R0 was defined as no microscopic residual cancer at the resection margins.

Tumor recurrence was diagnosed based on radiological evidence of intra-/extra-abdominal soft tissue and/or signs of peritoneal carcinomatosis. Three types of tumor recurrence were reported in this study – local recurrence, distant metastases and peritoneal carcinomatosis. Overall survival was defined as the time between the date of surgery until the date of death from any cause or the date of censoring. Data were censored at the last follow-up.

Data were analysed using R version 4.2.2. Continuous variables are presented as mean (± standard deviation) and median (range) for normally and non-normally distributed data, respectively. The two-sample T-test was used to compare normally distributed data, while the Mann-Whitney U test was used for non-normally distributed data. Categorical data are presented as frequencies (percentages). The Chi-square test or Fisher's exact test, when applicable, were applied to compare categorical variables. A two-tailed p-value < 0.05 was considered statistically significant.

PSM was applied to achieve balanced groups with comparable baseline characteristic and potentially minimizing confounding. Logistic regression was performed to estimate the propensity to undergo two different surgical procedures for gastric cancer. The R package ‘MatchIt’ (version 4.5.0) was used to create the final matched cohort. The matching was done using one-to-one nearest neighbour propensity score matching without replacement within a predefined propensity score radius (ie, caliper = 0.1) with a propensity score estimated using logistic regression of the treatment on the covariates. After matching, all standardized mean differences were below 0.1, indicating adequate balance. For the propensity-score matched cohort, paired methods were used in the analysis. The paired T-test was utilized for normally distributed data, and the Wilcoxon signed-rank test was employed for non-normally distributed data. Categorical variables were analysed using McNemar's test.

A multivariable binary logistic regression model with backward selection was used to examine the association between disease recurrence and clinicopathological parameters significant in the univariable analysis (p-value < 0.05). Median survival was estimated by using the Kaplan-Meier method and survival curves were plotted. The log-rank test was used to compare median survival between the groups.

A total number of 332 patients underwent distal subtotal gastrectomy for NEGA. B-I and B-II reconstructions were performed in 165 (49.7%) and 167 (50.3%) patients, respectively.

After applying PSM, 97 patients were analyzed in each group. These were comparable in terms of age, gender, and body mass index (Table 1). The total number of comorbidities was greater in patients receiving B-II reconstruction. Before PSM, the use of B-I reconstruction was associated with the smaller tumor size (4.5 vs. 6.2 cm, p = 0.001), tumor location in gastric antrum (97% vs. 79.6%, p = 0.001) and multi-organ resections were less common in this group (1.8 vs. 15%, p = 0.001). These differences became statistically non-significant after matching. Despite PSM, operative time with B-I remained shorter in comparison to B-II (143 vs. 165 min, p = 0.001). Other postoperative outcomes were similar in the two matched groups.

The two matched groups were not significantly different in terms of tumor size pT, pN, AJCC stages, R0 resection rates and tumor differentiation (Table 2). Significantly greater mean lymph node yield was observed in patients who had received B-I anastomosis (27 vs. 19, p = 0.001). Other lymph node-related parameters such as total number of positive lymph nodes and lymph node ratio were comparable between the two methods.

Median follow-up for the patients was 28 (2–150) months. Less than one-third (29%) of the patients received adjuvant chemotherapy overall and no significant differences were found between the groups (Table 3). The recurrence rate was lower following B-I in the unmatched cohort. The difference became statistically non-significant after applying PSM – 21.9% vs. 35.8%, p = 0.054. When analyzing for specific types of recurrence, local recurrence was significantly lower in patients with B-I reconstruction (3.1% vs. 11.6%, p = 0.022). No significant differences were found for other types of recurrence. Median survival was 38 (30–46) months, while 3- and 5-year survival rates were 52 and 32%, respectively. Overall survival was not significantly different between the groups after PSM (Figure 1).

FIGURE 1.

Uni- and multivariable analyses were performed to identify prognostic factors for tumor recurrence following distal subtotal gastrectomy for NEGA (Table 4). According to the univariable analysis, operative time, reconstruction method, pT and pN stages, total number of harvested lymph nodes, lymph node ratio and R1 resection were associated with recurrence. In the multivariable analysis, reconstruction method was not associated with recurrence. pT stage and lymph node ratio were the only independent predictors for tumor recurrence.