Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.

No long-term survival benefit with sustained-release 5-fluorouracil implants in patients with stages II and III gastric cancer.

BACKGROUND: The prognosis of gastric cancer in an advanced stage remains poor. The exact efficacy of the use of intraoperative sustained-release chemotherapy with 5-fluorouracil (5-FU) in advanced-stage gastric cancer is still unelucidated. AIM: To explore the long-term survival benefit of using sustained-release 5-FU implants in stage II and stage III gastric cancer patients. METHODS: Patients with gastric cancer in a locally advanced stage and who underwent an R0 radical resection between Jan 2014, to Dec 2016, in this single institution were included. Patients with pathological diagnoses other than adenocarcinoma were excluded. All included patients were grouped according to whether intraoperative sustained-release (SR) chemotherapy with 5-FU was used or not (NSR). The primary end-point was 5-year overall survival. Kaplan-Meier method with log-rank test was used to analyze the overall survival of patients and Cox analysis was used to analyze prognosis factors of these patients. RESULTS: In total, there were 563 patients with gastric cancer with locally advanced stage, who underwent an R0 radical resection. 309 patients were included in the final analysis. 219 (70.9%) were men, with an average age of 58.25 years. Furthermore, 56 (18.1%) received neoadjuvant chemotherapy, and 191 (61.8%) were in TNM stage III. In addition, 158 patients received intraoperative sustained-release chemotherapy with 5-FU and were included in the SR group, while the other 161 patients were included in the NSR group. The overall complication rate was 12.94% in the whole group and 10.81%, 16.46% in SR and NSR groups, respectively. There were no significant differences between the two groups in overall survival and complication rate (P > 0.05). The multivariate cox analysis indicated that only N Stage and neoadjuvant therapy were independent influencing factors of survival. CONCLUSION: Intraoperative sustained-release chemotherapy usage with 5-FU, did not improve the survival of patients who underwent an R0 radical resection in locally advanced stage of gastric cancer.

Investigation of the factors influencing surgical treatment of duodenal gastrointestinal stromal tumors.

BACKGROUND: Duodenal gastrointestinal stromal tumor (DGIST) is a rare tumor with a specific anatomic site and biological characteristics. As the incidence of lymph node metastasis is very low, the main treatment method is surgery. Two main surgical techniques (local resection and Whipple) are performed in patients with DGISTs. The critical question is which surgical technique to choose. AIM: To identify factors influencing the choice of surgery for DGISTs. METHODS: The clinicopathological data of patients with DGISTs who underwent surgery between January 1999 and January 2021 were analyzed. We used the Student's t-test or Mann-Whitney U-test and the χ 2 test or Fisher's exact test to determine the differences between the two groups of patients. Furthermore, we used logistic analysis to identify the relevant factors and independent factors related to the type of surgery. The Kaplan-Meier method was used to analyze the patient's survival information and Cox regression analysis was performed to determine prognostic risk factors. RESULTS: Overall, 86 patients were analyzed, including 43 men (50%) and 43 women (50%). We divided the patients into two groups based on surgical technique (local resection or Whipple surgery). There were no differences in the age, mitotic figures, and complications between the two groups; however, the tumor size, tumor location, risk grade, postoperative hospital stay, and abdominal drainage time were significantly different. Based on univariate logistic analysis, the Whipple procedure was chosen if the tumor size was ≥ 5.0 cm, the tumor was located in the descending part of the duodenum, or the risk grade was medium or high. In our research, the five-year overall survival rate of patients was more than 90%. We also describe two DGIST patients with liver metastases at first diagnosis and analyzed their management in order to provide advice on complicated cases. CONCLUSION: The Whipple procedure was performed if the primary tumor was in the descending part of the duodenum, tumor size was ≥ 5.0 cm, or the tumor risk grade was medium or high.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Risk factors for surgical-site infections after radical gastrectomy for gastric cancer: a study in China.

BACKGROUND: About 10% of patients get a surgical-site infection (SSI) after radical gastrectomy for gastric cancer, but SSI remains controversial among surgeons. The aim of this study was to explore the risk factors for SSIs after radical gastrectomy in patients with gastric cancer to guide clinical therapies and reduce the incidence of SSI. METHODS: The study was a retrospective cohort study in patients who underwent radical gastrectomy for gastric cancer. SSI was defined in accordance with the National Nosocomial Infection Surveillance System. We evaluated patient-related and peri-operative variables that could be risk factors for SSIs. The Chi-squared test and logistic regression analysis were used to assess the association between these risk factors and SSI. RESULTS: Among the 590 patients, 386 were men and 204 were women. The mean age was 56.6 (28-82) years and 14.2% (84/590) of these patients had an SSI. Among them, incisional SSI was observed in 23 patients (3.9%) and organ/space SSI in 61 patients (10.3%). Multivariate logistic regression analysis identified sex (odds ratios [ORs] = 2.548, and 95% confidence interval [CI]: 1.268-5.122, P = 0.009), total gastrectomy (OR = 2.327, 95% CI: 1.352-4.004, P = 0.002), albumin level (day 3 after surgery) <30 g/L (OR = 1.868, 95% CI: 1.066-3.274, P = 0.029), and post-operative total parenteral nutrition (OR = 2.318, 95% CI: 1.026-5.237, P = 0.043) as independent risk factors for SSI. CONCLUSIONS: SSI was common among patients after radical gastrectomy for gastric cancer. The method supporting post-operative nutrition and the duration of prophylactic antibiotics may be important modifiable influencing factors for SSI.

Role of D2 gastrectomy in gastric cancer with clinical para-aortic lymph node metastasis.

BACKGROUND: Owing to the technical difficulty of pathological diagnosis, imaging is still the most commonly used method for clinical diagnosis of para-aortic lymph node metastasis (PALM) and evaluation of therapeutic effects in gastric cancer, which leads to inevitable false-positive findings in imaging. Patients with clinical PALM may have entirely different pathological stages (stage IV or not), which require completely different treatment strategies. There is no consensus on whether surgical intervention should be implemented for this group of patients. In particular, the value of D2 gastrectomy in a multidisciplinary treatment (MDT) approach for advanced gastric cancer with clinical PALM remains unknown. AIM: To investigate the value of D2 gastrectomy in a MDT approach for gastric cancer patients with clinical PALM. METHODS: In this real-world study, clinico-pathological data of all gastric cancer patients treated at the Cancer Hospital, Chinese Academy of Medical Sciences between 2011 and 2016 were reviewed to identify those with clinically enlarged PALM. All the clinico-pathological data were prospectively documented in the patient medical record. For all the gastric cancer patients with advanced stage disease, especially those with suspicious distant metastasis, the treatment methods were determined by a multidisciplinary team. RESULTS: In total, 48 of 7077 primary gastric cancer patients were diagnosed as having clinical PALM without other distant metastases. All 48 patients received chemotherapy as the initial treatment. Complete or partial response was observed in 39.6% (19/48) of patients in overall and 52.1% (25/48) of patients in the primary tumor. Complete response of PALM was observed in 50.0% (24/48) of patients. After chemotherapy, 45.8% (22/48) of patients received D2 gastrectomy, and 12.5% (6/48) of patients received additional radiotherapy. The postoperative major complication rate and mortality were 27.3% (6/22) and 4.5% (1/22), respectively. The median overall survival and progression-free survival of all the patients were 18.9 and 12.1 mo, respectively. The median overall survival of patients who underwent surgical resection or not was 50.7 and 12.8 mo, respectively. The 3-year and 5-year survival rates were 56.8% and 47.3%, respectively, for patients who underwent D2 resection. Limited PALM and complete response of PALM after chemotherapy were identified as favorable factors for D2 gastrectomy. CONCLUSION: For gastric cancer patients with radiologically suspicious PALM that responds well to chemotherapy, D2 gastrectomy could be a safe and effective treatment and should be adopted in a MDT approach for gastric cancer with clinical PALM.