RESUMEN
BACKGROUND: Wnt5a is the key ligand of the noncanonical Wnt pathway, and receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a receptor associated with Wnt5a. The association between the noncanonical Wnt-signaling pathway and carcinogenesis in hepatocellular carcinoma (HCC) is unclear. This study investigated the significance of ROR2 expression in HCC. METHODS: The study examined ROR2 expression in liver cancer cell lines. Immunohistochemical staining of ROR2 was performed on 243 resected HCC specimens. The study investigated ROR2 expression and its association with clinicopathologic factors and prognosis. RESULTS: Findings showed that ROR2 was expressed in well-differentiated Huh7 and HepG2 cells, but not in poorly differentiated HLE and HLF cells. Expression of ROR2 was positive in 147 (60.5%) and negative in 96 (39.5%) HCC specimens. A significant association was shown between ROR2 negativity and high alpha-fetoprotein (AFP) level (P = 0.006), poor differentiation (P = 0.015), and Wnt5a negativity (P = 0.024). The 5-year overall survival (OS) rate for the ROR2-negative group (64.2 %) tended to be worse than for the ROR2-positive group (73.8%), but the difference was not significant (P = 0.312). The 5-year OS rate was 78.7% for the ROR2+Wnt5a+ group, 71.3 % for the ROR2+Wnt5a- group, 80.8% for the ROR2-Wnt5a+ group, and 60.5 % for the ROR2-Wnt5a- group. The OS in the ROR2-Wnt5a- group was significantly poorer than in the ROR2+Wnt5a+ group (P = 0.030). The multivariate analysis showed that Wnt5a-ROR2- was an independent prognostic factor (hazard ratio, 2.058; 95% confidence interval, 1.013-4.180; P = 0.045). CONCLUSIONS: The combination of ROR2 and Wnt5a may be a prognostic indicator for HCC. The Wnt5a/ROR2 signal pathway may be involved in the differentiation of HCC. This pathway may be a new therapeutic target for HCC.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Diferenciación Celular , Neoplasias Hepáticas/patología , Pronóstico , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Vía de Señalización WntRESUMEN
AIM: This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions. METHODS: Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n = 24) or after (n = 43) TKI approval ("beforeTKI" and "afterTKI" group, respectively). RESULTS: There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1 months, respectively; p = 0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9 months, respectively; p = 0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p < 0.001). CONCLUSION: These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.
RESUMEN
BACKGROUND: Postoperative pancreatic fistula (POPF) is a critical complication of laparoscopic gastrectomy (LG). However, there are no widely recognized anatomical landmarks to prevent POPF during LG. This study aimed to identify anatomical landmarks related to POPF occurrence during LG for gastric cancer and to develop an artificial intelligence (AI) navigation system for indicating these landmarks. METHODS: Dimpling lines (DLs)-depressions formed between the pancreas and surrounding organs-were defined as anatomical landmarks related to POPF. The DLs for the mesogastrium, intestine, and transverse mesocolon were named DMP, DIP, and DTP, respectively. We included 50 LG cases to develop the AI system (45/50 were used for training and 5/50 for adjusting the hyperparameters of the employed system). Regarding the validation of the AI system, DLs were assessed by an external evaluation committee using a Likert scale, and the pancreas was assessed using the Dice coefficient, with 10 prospectively registered cases. RESULTS: Six expert surgeons confirmed the efficacy of DLs as anatomical landmarks related to POPF in LG. An AI system was developed using a semantic segmentation model that indicated DLs in real-time when this system was synchronized during surgery. Additionally, the distribution of scores for DMP was significantly higher than that of the other DLs (p < 0.001), indicating the relatively high accuracy of this landmark. In addition, the Dice coefficient of the pancreas was 0.70. CONCLUSIONS: The DLs may be used as anatomical landmarks related to POPF occurrence. The developed AI navigation system can help visualize the DLs in real-time during LG.