HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

A Nomogram to Predict Individual Survival of Patients with Liver-Limited Metastases from Gastroenteropancreatic Neuroendocrine Neoplasms: A US Population-Based Cohort Analysis and Chinese Multicenter Cohort Validation Study.

INTRODUCTION: Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. METHODS: Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. RESULTS: A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all p < 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. CONCLUSION: A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.

The role of lymph node dissection in intrahepatic cholangiocarcinoma: a multicenter retrospective study.

BACKGROUND: Lymph node dissection (LND) is of great significance in intrahepatic cholangiocarcinoma (ICC). Although the National Comprehensive Cancer Network (NCCN) guidelines recommend routine LND in ICC, the effects of LND remains controversial. This study aimed to explore the role of LND and some related issues and of in ICC. METHODS: Patients were identified in two Chinese academic centers. Inverse probability of treatment weighting (IPTW) was used to reduce bias. Kaplan-Meier curves and Cox proportional hazards models were used to compare overall survival (OS) and disease-free survival (DFS). RESULTS: Of 232 patients, 177 (76.3%) underwent LND, and 71 (40.1%) had metastatic lymph nodes. A minimum of 6 lymph nodes were dissected in 66 patients (37.3%). LND did not improve the prognosis of ICC. LNM > 3 may have worse OS and DFS than LNM 1-3, especially in the LND > = 6 group. For patients who did not underwent LND, the adjuvant treatment group had better OS and DFS. CONCLUSIONS: The proportions of patients who underwent LND and removed > = 6 lymph nodes were not high enough. LND has no definite predictive effect on prognosis. Patients with 4 or more LNMs may have a worse prognosis than patients with 1-3 LNMs. Adjuvant therapy may benefit patients of nLND.

CDCA8, a mitosis-related gene, as a prospective pan-cancer biomarker: implications for survival prognosis and oncogenic immunology.

BACKGROUND: Human cell division cycle-associated protein 8 (CDCA8), a critical regulator of mitosis, has been identified as a prospective prognostic biomarker in several cancer types, including breast, colon, and lung cancers. This study analyzed the diagnostic/prognostic potential and clinical implications of CDCA8 across diverse cancers. METHODS: Bioinformatics and molecular experiments. RESULTS: Analyzing TCGA data via TIMER2 and GEPIA2 databases revealed significant up-regulation of CDCA8 in 23 cancer types compared to normal tissues. Prognostically, elevated CDCA8 expression correlated with poorer overall survival in KIRC, LUAD, and SKCM, emphasizing its potential as a prognostic marker. UALCAN analysis demonstrated CDCA8 up-regulation based on clinical variables, such as cancer stage, race, and gender, in these cancers. Epigenetic exploration indicated reduced CDCA8 promoter methylation levels in Kidney Renal Clear Cell Carcinoma (KIRC), Lung Adenocarcinoma (LUAD), and Skin Cutaneous Melanoma (SKCM) tissues compared to normal controls. Promoter methylation and mutational analyses showcased a hypomethylation and low mutation rate for CDCA8 in these cancers. Correlation analysis revealed positive associations between CDCA8 expression and infiltrating immune cells, particularly CD8+ and CD4+ T cells. Protein-protein interaction (PPI) network analysis unveiled key interacting proteins, while gene enrichment analysis highlighted their involvement in crucial cellular processes and pathways. Additionally, exploration of CDCA8-associated drugs through DrugBank presented potential therapeutic options for KIRC, LUAD, and SKCM. In vitro validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) confirmed elevated CDCA8 expression in LUAD cell lines (A549 and H1299) compared to control cell lines (Beas-2B and NL-20). CONCLUSION: This study provides concise insights into CDCA8's multifaceted role in KIRC, LUAD, and SKCM, covering expression patterns, diagnostic and prognostic relevance, epigenetic regulation, mutational landscape, immune infiltration, and therapeutic implications.

Surface Treat Method to Improve the Adhesion between Stainless Steel and Resin: A Review.

Combining metal and polymer into hybrid composite materials is finding increasing interest in many industries. Special attention is being paid to increase the adhesion between the metal and polymer interface. In this paper, the current research progress of surface treatment methods for improving the interfacial adhesion of stainless steel and resin is reviewed. It involves the stainless steel surface treatment method, resin surface treatment method, and adhesion test methods of stainless steel and resin. The methods of improving the interfacial adhesion of stainless steel and resin are summarized and prospected according to the research status.

Molecular diagnosis of pancreatobiliary tract cancer by detecting mutations and methylation changes in bile samples.

Background: Patients with pancreatobiliary tract cancer usually have a poor clinical outcome, with a 5-year overall survival rate below 20%. This is mainly associated with the late diagnosis. In addition, the standard-of-care for patients with malignant biliary stenosis involves a major surgery, the Whipple procedure. An accurate preoperative diagnosis, including differentiation from benign diseases, is critical to avoid unnecessary treatment. Here we developed BileScreen, a sensitive detection modality for the diagnosis of pancreatobiliary tract cancer based on massively parallel sequencing mutation and methylation changes in bile samples. Methods: A total of 338 patients, from five hospitals in China, with pancreatobiliary system disorders were enrolled in this study between November 2018 and October 2020, and 259 were included for the analysis of BileScreen. We profiled 23 gene mutations and 44 genes with methylation modifications in parallel from bile samples, and set up a model for the detection of malignancy based on multi-level biomarkers. Findings: We applied the BileScreen assay in a training cohort (n = 104) to set up the model and algorithm. The model was further evaluated in a validation cohort (n = 105), resulting in 92% sensitivity and 98% specificity. The performance of BileScreen was further assessed in a prospective test cohort (n = 50) of patients diagnosed with suspicious or negative pathology by endoscopic retrograde cholangiopancreatography and were confirmed in follow-up. BileScreen yielded 90% sensitivity and 80% specificity, and outcompeted serum carbohydrate antigen 19-9 in detecting pancreatobiliary tract cancer in all three cohorts, especially in terms of specificity. Interpretation: Taken together, BileScreen has the ability to interrogate mutations and methylation changes in bile samples in parallel, thus rendering it a potentially sensitive detection method to help in the diagnosis of pancreatobiliary tract cancer in a safe, convenient and less-invasive manner. Funding: This study was supported by the Capital's Funds for Health Improvement and Research (2020-2-4025 to S.H.), the National Natural Science Foundation of China (81972311 to H.Z.), CAMS Innovation Fund for Medical Sciences (CIFMS) (2017-12M-4-002 to H.Z.), the CAMS Innovation Fund for Medical Sciences(CIFMS) (2021-I2M-1-066 to CJQ), the Non-profit Central Research Institution Fund of Chinese Academy of Medical Sciences (2019PT310026 to H.Z.) and Sanming Project of Medicine in Shenzhen (SZSM202011010 to H.Z.).

Epidemiology of adenosarcoma and the inverse probability of treatment weighting (IPTW) adjusted survival analysis of lymph node dissection in uterine adenosarcoma.

The objective for the study was to analysis the epidemiology of adenosarcoma, and independent prognostic factors and impact of lymph node dissection (LND) of uterine adenosarcoma. Cases of patients with primary adenosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. Overall survival was analyzed by the Kaplan-Meier method and log-rank test. The differences in baseline covariates between the 2 groups were adjusted by inverse probability of treatment weighting method. The prognostic factors were identified by univariate and multivariate Cox regression analysis and hazard ratio and 95% confidence interval (CI) of covariates were also estimated. 1129 patients with pathological primary adenosarcoma between 2000 and 2016 were identified from the surveillance, epidemiology, and end results database. The only 4 patients were male. 1027 patients with primary uterine adenosarcoma, and 53.1% underwent LND and only 3.5% patients were with positive lymph node. Age, marital status, largest tumor size, tumor grade, T stage and chemotherapy were significantly correlated with survival. Race, tumor number, LND, and radiotherapy did not affect overall survival in patients. Inverse probability of treatment weighting-adjusted K-M curve showed that LND did not improve survival and lymph node metastasis (LNM) did not affect survival. The majority of primary adenosarcoma patients are female with high incidence of uterus and rare incidence of distant metastasis. Age, marital status, tumor size, T stage, grade, and chemotherapy are independent prognostic factors of uterine adenosarcoma. LNM was not a significant prognostic risk factor, and LND did not benefit survival.

The first successful treatment and genetic sequencing of primary hepatic adenosarcoma with sarcomatous overgrowth: a case report.

Adenosarcoma is a rare type of tumor with a mixture of epithelial and stromal components and often occurs in the female reproductive system. Primary hepatic adenosarcoma (PHAS) is extremely rare, with only two cases reported so far. Both patients had poor outcomes. Here, we report the case of a 36-year-old man with pain under the xiphoid process who was diagnosed with a bile duct tumor. He was treated with adjuvant radiotherapy when surgery was performed on him. Pathologically, the tumor contained benign epithelial tissue, and the submucosa of the bile duct in the liver showed infiltrating growth of spindle cell components. The cells were dense, mildly heterotypic, and occasionally mitotic, and the patient was diagnosed with PHAS. Whole-exome sequencing results showed that a total of 12 mutations were shared by the two tissues. The patient received adjuvant radiotherapy and he was tumor-free until 31 months postoperatively. This case will provide some references of the disease to other researchers.

Milling Parameter Optimization of Continuous-Glass-Fiber-Reinforced-Polypropylene Laminate.

The composite-material laminate structure will inevitably encounter connection problems in use. Among them, mechanical connections are widely used in aerospace, automotive and other fields because of their high connection efficiency and reliable connection performance. Milling parameters are important for the opening quality. In this paper, continuous-glass-fiber-reinforced-polypropylene (GFRPP) laminates were chosen to investigate the effects of different cutters and process parameters on the hole quality. The delamination factor and burr area were taken as the index to characterize the opening quality. After determining the optimal milling tool, the process window was obtained according to the appearance of the milling hole. In the selected process parameter, the maximum temperature did not reach the PP melting temperature. The best hole quality was achieved when the spindle speed was 18,000 r/min and the feed speed was 1500 mm/min with the corn milling cutter.

Parametric Investigation into the Shear Strength of Adhesively Bonded Single-Lap Joints.

In this paper, the shear strength of adhesively bonded single-lap joints were experimentally and numerically investigated. Based on the validated simulation, the effects of lap length, adhesive layer thickness, adhesive layer shape, adhesive layer overflow length, and laminate lay-up on the shear strength of adhesively bonded single-lap joints were studied. The load-displacement curves and shear strength under different parameters were compared. It was shown that the shear strength of single-lap joints gradually decreases with the increase of lap length and adhesive layer thickness, which were 53.83% and 16.15%, respectively. Considering the potential condition in fabrication, the adhesive layer shape and adhesive layer overflow length were also investigated. The adhesive with normal and triangle shape owned the comparable shear strength, which was higher than the arc one. The shear strength increased by 19.37% from 18.43 MPa to 22.00 MPa with increasing the adhesive layer overflow length to 50% of lap length. It was beneficial for shear strength to increase the adhesive layer overflow length to 50% of lap length. Among the selected four lay-ups, [0]16s had the highest shear strength, which was nearly 3 times greater than the one of [90]16s. In the real process preparation, increasing the number of 0° layers, selecting the appropriate lap length and thickness of the adhesive layer, and controlling the shape and length of the adhesive layer overflow are of great help to improve the tensile shear strength of the single-lap glue joint.

Mechanical Property of Long Glass Fiber Reinforced Polypropylene Composite: From Material to Car Seat Frame and Bumper Beam.

Long Fiber Reinforced Thermoplastic (LFT) is a lightweight, high-strength, and easy-to-recycle new vehicle composite material, and has good mechanical properties, heat resistance, and weather resistance, which has found increasing application in automobile industry. It is of importance to understand the relationship between micro phase, macro-mechanical properties and the structural performance of automobile components. This article evaluates the performance of LFT from the level of material to automobile components. The mechanical properties of LFT were numerically and theoretically predicted to provide instruction for the next material choice. Two typical structural components, namely, car seat frame and bumper beam, were selected to evaluate the performance of LGF/PP compared with other competing materials in terms of mechanical properties and cost. In the case of the same volume, the seat frame of 40% LECT/PP composite material is lighter and cheaper, which is conducive to energy saving and emission reduction. It was shown that the 40% LECT/PA66 car bumper beam had a higher energy absorption ratio, lighter weight, higher specific energy absorption, and advantageous material cost. LFT is a promising candidate for existing automobile components with its performance fulfilling the requirements.

RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy.

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138-/- mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation.

The role of lymph node dissection and a new N-staging system for intrahepatic cholangiocarcinoma: a study from the SEER database.

BACKGROUND: Although the National Comprehensive Cancer Network guidelines recommend routine lymph node dissection (LND) in intrahepatic cholangiocarcinoma (ICC), the role of LND remains controversial, and the node (N) stage is oversimplified. METHODS: Patients were identified from the Surveillance, Epidemiology, and End Results research data 18 (SEER 18). Propensity score matching (PSM) was used to reduce bias, and Kaplan-Meier curves and Cox proportional hazards models were used to compare overall survival (OS). The best cutoff values were found using X-tile software. RESULTS: Of 2037 patients included in SEER 18, 1147 underwent LND (56.3%); 389 (34.3%) had pathologically confirmed lymph node metastasis (LNM), and 316 (27.6%) had at least 6 LNDs. The median OS was worse for LND patients (34 months vs. 40 months, respectively), and this result remained after PSM. Male sex, age ≥60 years, tumor size > 5 cm, and LNM were independent prognostic risk factors for ICC. LNM ≥3 was associated with worse OS. CONCLUSIONS: Only a few LNDs met the requirements per the guidelines. LND does not improve OS in ICC, and the best approach to LND and a better N staging method should be explored further.

Current situation and trends of online academic activities for oncologists during the COVID-19 pandemic: a multicenter survey.

BACKGROUND: The present study aimed to investigate the current situation and future trends of online academic activities for oncologists during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: From April 22 to May 5, 2020, a multicenter survey was conducted using an online questionnaire platform. To compare categorical variables, χ2-test, the kappa consistency analysis, and Wilcoxon rank sum test were applied. For all statistical hypotheses, P<0.05 was considered significant. RESULTS: In the present study, 2,120 oncologists participated in the survey. Of these, 2,035 respondents participated in online academic activities. During the pandemic, online academic activities significantly increased [oncologists who participated in online academic activities ≥60%: 64.58% (during the pandemic) vs. 10.90% (before the pandemic), Cohen's kappa coefficient =0.0499, P<0.001]. The findings indicated that 90.6% of respondents considered that the online academic activities would become a future trend. The main reason for the increase in online academic activities was due to in-person academic conferences and diagnoses/treatment being affected by the pandemic. Both speakers/chairs and audiences agreed that online academic activities resulted in reduced stress (61.15% vs. 67.26%, respectively; χ2=7.009, P=0.03). In the present study, 62.21% of audiences considered that the recording function of online activities was very important (score 5), while only 53.86% of the speakers had the same opinion (Z=-3.5340, P<0.001). Compared with provincial capital cities and other cities, the participants from first-tier cities thought that online academic activities required significant physical energy (χ2=6.41, P=0.040), and were more reluctant for the playback of activity contents (χ2=9.33, P=0.002) and the screenshot of activity contents (χ2=41.99, P<0.001). CONCLUSIONS: During the COVID-19 pandemic, online academic activities have become the main form of academic exchanges for oncologists. Taking full advantage of online academic activities and paying adequate attention to the participants' requirements with different roles and titles, and from different cities, are key to improving the quality of and involvement in online academic activities.

PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies, and it's expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. METHODS: Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. RESULTS: Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. CONCLUSIONS: These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.

P53-R273H mutation enhances colorectal cancer stemness through regulating specific lncRNAs.

BACKGROUND: TP53 is one of the most frequently mutated genes among all cancer types, and TP53 mutants occur more than 60% in colorectal cancer (CRC). Among all mutants, there are three hot spots, including p53-R175H, p53-R248W and p53-R273H. Emerging evidence attributes cancer carcinogenesis to cancer stem cells (CSCs). Long noncoding RNAs (lncRNAs) play crucial roles in maintaining the stemness of CSCs. However, it is unknown if mutant p53-regulated lncRNAs are implicated in the maintenance of CSC stemness. METHODS: RNA-sequencing (RNA-seq) and ChIP-sequencing (ChIP-seq) were used to trace the lncRNA network regulated by p53-R273H in HCT116 endogenous p53 point mutant spheroid cells generated by the somatic cell knock-in method. RT-qPCR was used to detect lncRNA expression patterns, verifying the bioinformatics analysis. Transwell, spheroid formation, fluorescence activated cell sorter (FACS), xenograft nude mouse model, tumor frequency assessed by extreme limiting dilution analysis (ELDA), Western blot assays and chemoresistance analysis were performed to elucidate the functions and possible mechanism of lnc273-31 and lnc273-34 in cancer stem cells. RESULTS: p53-R273H exhibited more characteristics of CSC than p53-R175H and p53-R248W. RNA-seq profiling identified 37 up regulated and 4 down regulated differentially expressed lncRNAs regulated by p53-R273H. Combined with ChIP-seq profiling, we further verified two lncRNAs, named as lnc273-31 and lnc273-34, were essential in the maintenance of CSC stemness. Further investigation illustrated that lnc273-31 or lnc273-34 depletion dramatically diminished colorectal cancer migration, invasion, cancer stem cell self-renewal and chemoresistance in vitro. Moreover, the absence of lnc273-31 or lnc273-34 dramatically delayed cancer initiation and tumorigenic cell frequency in vivo. Also, lnc273-31 and lnc273-34 have an impact on epithelial-to mesenchymal transition (EMT). Finally, lnc273-31 and lnc273-34 were significantly highly expressed in CRC tissues with p53-R273H mutation compared to those with wildtype p53. CONCLUSIONS: The present study unveiled a high-confidence set of lncRNAs regulated by p53-R273H specific in colorectal CSCs. Furthermore, we demonstrated that two of them, lnc273-31 and lnc273-34, were required for colorectal CSC self-renewal, tumor propagation and chemoresistance. Also, the expression of these two lncRNAs augmented in colorectal cancer patient samples with p53-R273H mutation. These two lncRNAs may serve as promising predictors for patients with p53-R273H mutation and are vital for chemotherapy.

Report of one case: surgical treatment for neuroendocrine tumors.

A 68-year-old female patient was admitted to our center due to anorexia and epigastric pain for 2 months. Plain abdominal CT revealed a splenic space-occupying lesion; it had invaded the greater curvature of stomach and had blurred margin with the tail of pancreas. The longest diameter was about 10.7 cm. The lesion was considered to be malignant, accompanied with peritoneal nodules; the possibility of lymph node metastasis could not be ruled out. MRI revealed that the mass was located in front of the spleen, with irregular shape and unclear margin. Part of the mass invaded the greater curvature of stomach and part of it had blurred margin with the tail of pancreas. The largest cross section sized 9.4 cm × 6.9 cm. It showed intermediate and high signals on T2WI/FS, which corresponded to restricted diffusion on DWI sequences. The levels of tumor markers including CA19-9, CA242, and CEA were normal. Exploratory laparotomy + resection of the body and tail of pancreas + resection of part of stomach wall + removal of nodules on liver surface were performed. Postoperative pathology confirmed that the lesion was a neuroendocrine tumor (G1).

Prognostic Value of Lymph Node Ratio in Patients Receiving Combined Surgical Resection for Gastric Cancer Liver Metastasis: Results from Two National Centers in China.

The purpose of this study was to evaluate the prognostic value of lymph node ratio (LNR) in patients with gastric cancer liver metastasis (GCLM) who received combined surgical resection. A retrospective analysis of 46 patients from two hospitals was conducted. Patients were dichotomized into two groups (high LNR and low LNR) by the median value of LNR. The overall survival (OS) and recurrence-free survival (RFS) were analyzed by the Kaplan-Meier method with the log-rank test. The Cox proportional hazard model was used to carry out the subsequent multivariate analyses. And the relationship between LNR and clinicopathological characteristics was assessed. The cut-off value defining elevated LNR was 0.347. With a median follow-up of 67.5 months, the median OS and RFS of the patients were 17 and 9.5 months, respectively. Six patients survived for >5 years after surgery. Patients with higher LNR had significantly shorter OS and RFS than those with lower LNR. In the multivariate analyses, higher LNR and multiple liver metastatic tumors were identified as the independent prognostic factors for both OS and RFS. Elevated LNR was significantly associated with advanced pN stage (P <0.001), larger primary tumor size (P = 0.046), the presence of microvascular invasion (P = 0.008), and neoadjuvant chemotherapy (P = 0.004). LNR may be prognostic indicator for patients with GCLM treated by synchronous surgical resection. Patients with lower LNR and single liver metastasis may gain more survival benefits from the surgical resection. Further prospective studies with reasonable study design are warranted.