In total patients men and women with a
In total, 215 patients (124 men and 91 women), with a median age at operation of 53 years (range, 16–89 years) were included. Pathological staging according to the seventh edition of the AJCC Manual showed Stages 0, I, and II for three patients, 142 patients, and 70 patients, respectively. Overall, 180 distal subtotal gastrectomies and 35 total gastrectomies were performed. All patients had undergone cholesterol absorption inhibitor node dissections [D1 or more (over D1), 197 patients; D0, 18 patients]. The extent of lymph node dissection was classified according to the Japanese gastric cancer treatment guidelines 2010 (version 3). Lymph node dissection around the liver hilum was not routinely performed in our patients. Moreover, splenectomy was also not a routine procedure accompanying total gastrectomy. Thirty-seven patients received postoperative concurrent chemoradiation therapy; 24 patients had type 2 diabetes mellitus.
The cumulative incidence of gallstones after gastrectomy was evaluated using the Kaplan–Meier method. Univariate analysis of risk factors for gallstone formation was performed using the Chi-square and Fisher\'s exact tests for categorical variables and Student t test for numerical variables. Multivariate analysis was performed using a logistic regression model. A p value < 0.05 was considered statistically significant. Statistical analyses were performed using SAS software, version 9.3 (SAS Institute, Cary, NC, USA).
Results Gallstones were detected in 46 of the 215 patients (21.4%) during a median follow-up period of 3.5 years (range, 0.5–14.5 years). Gallstones were diagnosed at a median of 2.3 years (range, 0.5–11.5 years) after gastrectomy. Half of the patients with gallstones were diagnosed within 2 years after surgery, mostly during routine abdominal ultrasonography. The incidence of new cases peaked 1–2 years after gastrectomy and then gradually decreased (Figure 1). The cumulative incidence of gallstones at 5 years and 10 years after gastrectomy was 18% and 20%, respectively (Figure 2). Furthermore, univariate and multivariate analyses revealed that an age at operation of ≥ 60 years, type 2 diabetes mellitus, total gastrectomy, and Billroth II reconstruction (vs. Billroth I) were independent risk factors for gallstone formation (Tables 1 and 2). Seven patients with complicated gallstones, accounting for 3.3% of all gastrectomy patients and 15.2% of patients with newly diagnosed gallstones, were clinically diagnosed with acute cholecystitis. Three patients had undergone cholecystectomy soon after visiting the emergency department of other hospitals, three patients had undergone urgent operations in our hospital, and one patient refused surgery. Moreover, three patients had common bile duct stones with associated bile duct obstruction and infection. An episode of acute cholecystitis occurred at a median of 4.3 years (range, 1.7–6 years) after the initial surgery. This event was more significant in patients who had undergone total gastrectomy (5 of 14; 35.7%) than in those who had undergone distal subtotal gastrectomy (2 of 32; 6.2%; p = 0.02). Diabetes mellitus and age at operation were unassociated with complicated gallstone.
Discussion Our study showed a cumulative incidence of gallstones in 21.4% (46 of 215 patients), which is consistent with previous reports. A pooled analysis of 16 studies on gallstone formation after upper gastrointestinal surgery reported an incidence of 17.5%. Moreover, a Peruvian observational case series analyzed the frequency and development of gallbladder stones after subtotal and total gastrectomy and reported a 19.6% incidence, with a mean development period of 3.1 years. In this study, the cumulative incidence of gallstones at 5 years and 10 years after gastrectomy was 18% and 20%, respectively, which is consistent with the report of Kobayashi et al (13.6% and 22.1%, respectively). Factors associated with gallstone formation after gastrectomy include lymph node dissection, extent of gastrectomy, and method of reconstruction. Increased gallstone formation has been observed after radical gastrectomy compared with that after simple gastrectomy. More extensive lymph node dissection results in higher incidences of gallstone formation. In our study, almost all patients had undergone an over-D1 dissection; therefore, this difference was not observed. Kobayashi et al reported that the dissection of lymph nodes in the hepatoduodenal ligament was the most significant risk factor for gallstones. However, a thorough dissection of the nodes of the hepatoduodenal ligament was not routinely performed in our patients.