This retrospective study identified 88 consecutive inpatients who underwent primary hepatic resection for CRLM in the Department of Surgery at Onomichi General Hospital between June 2006 and April 2019. It was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. The study design was approved by our institutional review board (OJH-201509), and all patients provided informed consent for their treatment.
The initial surgery was performed using a laparoscopic or open method. The extent of resection was determined by the location of the tumor. Partial resection was selected if possible; if not, segment resection or lobectomy was selected to preserve liver function. The Pringle method was used as much as possible to control bleeding.
Fifty-eight patients received NAC. The regimens were as follows: 1) 5-fluorouracil (5FU), leucovorin (LV), and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) (n = 34); 2) 5FU, LV, and irinotecan (FOLFILI, n = 10); and 3) tegafur/gimeracil/oteracil (TS-1) or tegafur/uracil with either LV (UFT/UZEL) or capecitabine (n = 14). The FOLFOX and FOLFILLI regimens also included a molecularly targeted agent (bevacizumab, cetuximab, or panitumumab) if needed. the standard treatment at our facility has been NAC. The administration period depends on the case and regimen, but usually includes six treatment courses. Upfront hepatectomy was performed in the patients who refused to undergo NAC and in those whose general condition contraindicated NAC.
Complications and morbidity
Complications were classified as described by Dindo et al . Postoperative complications were defined as complications of grade IIIa or greater and postoperative mortality was defined as any death that occurred within 30 days after surgery. Survival values were calculated from the date of surgery.
All patients were followed until death and underwent annual follow-ups consisting of abdominal ultrasonography and laboratory tests for tumor markers, namely, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen. Dynamic computed tomography (CT) was performed every 6 months. If a definitive diagnosis of recurrence could not be established based on tumor marker data, ultrasonography-guided biopsy imaging (CT, magnetic resonance imaging, endoscopic ultrasonography, or fluorodeoxyglucose-positron emission tomography) was performed.
The following six preoperative factors were used to create the nomogram for DFS: synchronous metastasis (3 points); positive primary lymph node (3 points); tumor number, (4 points for 2–4 tumors and 9 points for ≥5 tumors); largest tumor diameter >5 cm (2 points); extrahepatic metastasis at hepatectomy (4 points); and preoperative CA19-9 level >100 (4 points). Zero, 5, 10, and >10 points corresponded to estimated median DFS times of >8.4 years, 1.9 years, 1 year, and <0.6 years, respectively. The total preoperative Beppu scores ranged from 0 to 25 points.
Recurrence-free survival (RFS) rates were determined using the Kaplan-Meier method and the log-rank test. Multivariate analyses for RFS were performed using Cox’s regression model. Appropriate calibration of the model was indicated by a P value of 0.620 in the Hosmer-Lemeshow test, and good discrimination was indicated by a C-statistic of 0.773 with a 95% confidence interval (CI) of 0.662–0.884 and a P value <0.001. Propensity score analysis using inverse probability of treatment weighting (IPTW) was performed to overcome bias related to the different distributions of the covariates between NAC recipients and non-recipients. After IPTW processing, differences in RFS between these groups were tested using Cox regression and multiple logistic regression analyses. Two-tailed P-values <0.05 were considered statistically significant, and all analyses were performed using SPSS software (version 24; IBM, Armonk, NY, USA).