No abstract

N6-methyladenosine (m 6 A), the most abundant internal RNA modification, serves a critical role in cancer development. However, the clinical implications of m 6 A in hepatocellular carcinoma (HCC) remain unclear. The present study sought to reveal the potential roles of m 6 A readers, which recognize m 6 A, in HCC. A total of 177 HCC and paired non-cancerous liver tissues from patients who underwent hepatectomy were analysed using quantitative PCR for the expression of m 6 A readers: YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 2 (YTHDF2). The expression levels of both YTHDF1 and YTHDF2 were not significantly different between tumour and non-cancerous tissues (P= 0.93 and P= 0.7, respectively). Analysis of the association between clinical features and m 6 A reader expression revealed that YTHDF1 expression was associated with formation of capsule (P= 0.02), whereas low YTHDF2 expression was associated with septal formation (P= 0.02). Furthermore, high YTHDF1 expression and high YTHDF2 expression were significantly associated with shorter recurrence-free survival (RFS) [YTHDF1: Mean survival time (MST), 34.0 vs. 19.0 months, P= 0.014; YTHDF2: MST, 30.1 vs. 12.9 months, P= 0.0032], whereas YTHDF1 and YTHDF2 expression was not significantly associated with overall survival (OS) (YTHDF1: MST, 99.4 vs. 70.2 months, P= 0.74; YTHDF2: MST, 98.4 vs. 64.1 months, P= 0.28). According to multivariate analysis, serosal invasion [hazard ratio (HR), 2.39; 95% CI 1.30-4.42; P= 0.005), portal vein or hepatic vein invasion (HR, 2.82; 95% CI 1.26-6.28; P= 0.01) and YTHDF2 expression in HCC tissues (HR, 1.85; 95% CI 1.09-3.15; P= 0.02) were identified as significant independent prognostic factors for RFS. α-fetoprotein (HR, 1.79; 95% CI 1.10-2.92; P= 0.02), serosal invasion (HR, 1.99; 95% CI 1.17-3.34; P= 0.01) and portal vein or hepatic vein invasion (HR, 3.02; 95% CI 1.38-6.61; P= 0.006) were identified as significant independent prognostic factors for OS. In conclusion, the present study revealed that high YTHDF2 expression, an m 6 A reader, in HCC tissues was associated with cancer recurrence.

BackgroundAdvanced gastric cancer frequently recurs even after radical resection followed by adjuvant chemotherapy. The aim of this study was to evaluate the relationship between pathological infiltrative pattern (INF) and initial recurrence patterns in patients with stage II/III gastric cancer using a large multicenter database.MethodsWe retrospectively analyzed 1098 eligible patients who underwent curative gastrectomy for stage II/III gastric cancer at nine institutions between 2010 and 2014. Patients were categorized into the INF‐a/b and INF‐c groups and adjusted using propensity score matching.ResultsAfter propensity score matching, 686 patients (343 for each) were classified in the INF‐a/b and INF‐c groups. There were no significant differences in overall and disease‐free survival between the two groups. In the INF‐a/b group, frequencies of recurrence at the peritoneum, lymph node, and liver were equivalent. In contrast, the peritoneum was the most frequent site and accounted for 60% of the total recurrences in the INF‐c group. The cumulative peritoneal recurrence rate was significantly higher in the INF‐c group than in the INF‐a/b group (hazard ratio 2.47). INF‐c was a significant risk factor for peritoneal recurrences in most subgroups including age, sex, macroscopic type, tumor differentiation, and disease stage, and whether the postoperative treatment was given. Multivariate analysis identified INF‐c as an independent risk factor for peritoneal recurrences. The cumulative liver recurrence rate was significantly higher in the INF‐a/b group than in the INF‐c group (hazard ratio 3.44).ConclusionsINF may represent an important predictor of recurrence patterns after curative resection of stage II/III gastric cancer.

Background/Aim: N6-Methyladenosine (m6A), the most abundant internal modification of RNA, plays a critical role in cancer development. However, the clinical implications of m 6 A in hepatocellular carcinoma (HCC) remain unclear. Materials and Methods: We analyzed 177 HCC and paired noncancerous liver tissues from patients who underwent hepatectomy according to global m 6 A quantification and expression of m 6 A demethylases fat mass and obesity-associated protein (FTO) and alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5). Results: The global m 6 A quantification revealed no significant difference between HCC and non-cancerous tissue. The expression of m 6 A demethylases FTO and ALKBH5, was significantly lower in HCC than in non-cancerous tissues (both p<0.001). Furthermore, low ALKBH5 expression in non-cancerous tissues was significantly correlated with worse recurrence-free survival (median of 16.3 vs. 38.9 months, p=0.001). Conclusion: m 6 A in HCC and its demethylase in surrounding non-cancerous liver tissues might be involved in inherent mechanisms for HCC development and affect malignant potential after HCC resection.

Patients with resectable pancreatic cancer are considered to already have micro-distant metastasis, because most of the recurrence patterns postoperatively are distant metastases. Multimodal treatment dramatically improves prognosis; thus, micro-distant metastasis is considered to be controlled by chemotherapy. The survival benefit of “regional lymph node dissection” for pancreatic head cancer remains unclear. We reviewed the literature that could be helpful in determining the appropriate resection range. Regional lymph nodes with no suspected metastases on preoperative imaging may become areas treated with preoperative and postoperative adjuvant chemotherapy. Many studies have reported that the R0 resection rate is associated with prognosis. Thus, “dissection to achieve R0 resection” is required. The recent development of high-quality computed tomography has made it possible to evaluate the extent of cancer infiltration. Therefore, it is possible to simulate the dissection range to achieve R0 resection preoperatively. However, it is often difficult to distinguish between areas of inflammatory changes and cancer infiltration during resection. Even if the “dissection to achieve R0 resection” range is simulated based on the computed tomography evaluation, it is difficult to identify the range intraoperatively. It is necessary to be aware of anatomical landmarks to determine the appropriate dissection range during surgery.