Evaluation of postoperative quality of life by PGSAS-45 following local gastrectomy based on the sentinel lymph node concept in early gastric cancer
基于前哨淋巴结概念的胃癌局部切除术后 PGSAS-45 生活质量评价
- 作者列表："Okubo, Keishi","Arigami, Takaaki","Matsushita, Daisuke","Sasaki, Ken","Kijima, Takashi","Noda, Masahiro","Uenosono, Yoshikazu","Yanagita, Shigehiro","Ishigami, Sumiya","Maemura, Kosei","Natsugoe, Shoji
Background The usefulness of sentinel node navigation surgery (SNNS) for early gastric cancer has been demonstrated in a multicenter prospective study. However, quality of life (QOL) after local resection remains unclear. This present study investigated QOL after local resection and distal gastrectomy. Methods We examined 69 patients who underwent laparoscopic distal gastrectomy (LADG) ( n = 44) and laparoscopic local resection (LLR) ( n = 25) in our hospital between September 2011 and May 2018. We conducted a combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET) with SNNS as LLR. All patients had pStage I or II and none had received adjuvant chemotherapy. We evaluated QOL using the postgastrectomy syndrome assessment scale questionnaire (PGSAS-45) 1, 6, and 12 months after surgery. Results In PGSAS-45, no significant differences were observed between LLR and LADG at 1 and 6 months after surgery. At 12 months, the LLR group scored better for some of the subscales (SS). In the endoscopic evaluation, the LLR group showed significant improvements in residual gastritis at 6 months ( P = 0.006) and esophageal reflux and residual gastritis at 12 months ( P = 0.021 and P = 0.017). A significant difference was observed in the prognostic nutritional index, which was assessed using serum samples, between the two groups at 6 months ( P = 0.028). The body weight ratio was better in the LLR group than in the LADG group at 6 and 12 months ( P = 0.041 and P = 0.007, respectively). Conclusions CLEAN-NET with SNNS preserved a better QOL and nutrition status than LADG in patients with early gastric cancer.
背景一项多中心前瞻性研究证实了前哨淋巴结导航手术 (SNNS) 对早期胃癌的有效性。然而，局部切除后的生活质量 (QOL) 仍不清楚。本研究调查了局部切除和远端胃切除术后的 QOL。方法我们检查了 69 例接受腹腔镜远端胃切除术 (LADG) (n = 44) 和腹腔镜局部切除术 (LLR) (n = 25) 的患者。我院于 2011年9月至 2018年5月。我们采用 SNNS 作为 LLR 的非暴露技术 (CLEAN-NET) 进行了腹腔镜和内镜联合手术治疗肿瘤。所有患者均处于 I 期或 II 期，均未接受辅助化疗。我们在术后 1 、 6 和 12 个月使用胃切除术后综合征评估量表问卷 (PGSAS-45) 评估 QOL。结果在 PGSAS-45 中，术后 1 个月和 6 个月的 LLR 和 LADG 之间无显著差异。12 个月时，LLR 组的一些分量表 (SS) 得分较高。在内镜评估中，LLR 组在 6 个月时残留胃炎明显改善 (P = 0.006) 12 个月时食管反流和残余胃炎 (P = 0.021 和 P = 0.017)。在 6 个月时，使用血清样本评估两组之间的预后营养指数存在显著差异 (P = 0.028)。在 6 个月和 12 个月时，LLR 组的体重比优于 LADG 组 (分别为 P = 0.041 和 P = 0.007)。结论与 LADG 相比，SNNS 联合 CLEAN-NET 能更好地保留早期胃癌患者的 QOL 和营养状况。
METHODS::Aims: Radiotherapy is predominantly used as one of the treatment modalities to treat local tumor in colorectal cancer (CRC). Hindrance in disease treatment can be attributed to radio-tolerance of cancer stem cells (CSCs) subsistence in the tumor. Understanding the radio-resistant property of CSCs might help in the accomplishment of targeted radiotherapy treatment and increased disease-free survival. Telomeric RAP1 contributes in modulation of various transcription factors leading to aberrant cell proliferation and tumor cell migration. Therefore, we investigated the role of RAP1 in maintaining resistance phenotype and acquired stemness in radio-resistant cells.Main Methods: Characterization of HCT116 derived radio-resistant cell (HCT116RR) was performed by cell survival and DNA damage profiling. RAP1 silenced cells were investigated for DNA damage and expression of CSC markers through western blotting and Real-time PCR post-irradiation. Molecular docking and co-immunoprecipitation study were performed to investigate RAP1 and KLF4 interaction followed by RAP1 protein status profiling in CRC patient.Key findings: We established radio-resistant cells, which showed tolerance to radiotherapy and elevated expression of CSC markers along with RAP1. RAP1 silencing showed enhanced DNA damage and reduced expression of CSC markers post-irradiation. We observed strong physical interaction between RAP1 and KLF4 protein. Furthermore, higher RAP1 expression was observed in the tumor of CRC patients. Dataset analysis also revealed that high expression of RAP1 expression is associated with poor prognosis.Significance: We conclude that higher expression ofRAP1 implicates its possible role in promoting radio-resistance in CRC cells by modulating DNA damage and CSC phenotype.
METHODS::Cancer stem-like cells are rare immortal cells within tumor, which are thought to play important roles in ionizing radiation (IR) therapy-resistance. Quercetin is a natural flavonoid with potential anti-cancer properties without significant cytotoxicity in normal tissues. In this study, we demonstrated that quercetin-IR combination treatment exhibited more dramatic anti-cancer effect than either quercetin or IR treatment alone via targeting colon cancer stem cells (CSCs) and inhibiting the Notch-1 signaling. These effects were further verified by in vivo studies which showed remarkable decrease of the CSCs markers and the expression of Notch-1 signaling proteins in human colon cancer xenografts in nude mice. Co-treatment with quercetin and low dose of radiation significantly reduced the expressions of all five proteins of γ-secretase complex in HT-29 and DLD-1 cells. In addition, ectopic expression of the Notch intracellular domain (NICD) partly reversed the inhibition effects by the combination therapy. In conclusion, our results indicated that the combination of quercetin (20 μM) and IR (5Gy) might be a promising therapeutic strategy for colon cancer treatment by targeting colon cancer stem-like cells and inhibiting the Notch-1 signaling. In future studies, we intend to further explore the potential therapeutic efficacy of the quercetin-radiation combination treatment in clinical trials.
METHODS:OBJECTIVES:Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial. MATERIALS AND METHODS:Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer. Positivity for and fractional abundance of meth-ctDNA in baseline samples were estimated. Overall survival (OS) and the rate of distant metastases were compared between meth-ctDNA positive and negative patients; other prognostic factors were controlled for in multivariate Cox regression. Importance of quantitative load was examined by considering the fractional abundance of meth-ctDNA relative to total circulating DNA. RESULTS:Baseline serum samples were available for 146 patients. In total, 30 patients had presence of meth-ctDNA, with no correlation with cT (P=0.8) or cN (P=0.6) stages. Median follow-up was 10.6 years for OS and 5.1 years for freedom from distant metastases. Patients with meth-ctDNA had significantly worse 5-year OS (47% vs. 69%), even when controlling for other prognostic factors (hazard ratio=2.08; 95% confidence interval, 1.23-1.51). This seemed mainly driven by disparity in the rate of distant metastases (55% vs. 72% at 5 y, P=0.01); hazard ratio=2.20 (95% confidence interval, 1.19-4.07, P=0.01) in multivariate analysis. Increased quantitative load was highly significant for worse outcomes. CONCLUSIONS:Meth-ctDNA could be a potential prognostic marker in the neoadjuvant setting and may, if validated, identify patients at increased risk of distant metastases.