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Abstract Background Colorectal neuroendocrine tumors with liver metastases (CRNELM) are associated with a poorer prognosis compared to their nonmetastatic counterparts. A comprehensive understanding of the tumor microenvironment (TME) heterogeneity between primary lesions (PL) and liver metastases (LM) could provide crucial insights for enhancing clinical management strategies for these patients. Methods We utilized single-cell RNA sequencing to analyze fresh tissue samples from CRNELM patients, aiming to elucidate the variations in TME between PL and LM. Complementary multidimensional validation was achieved through spatial transcriptomics, bulk RNA sequencing, and multiplex immunohistochemistry/immunofluorescence. Results Our single-cell RNA sequencing analysis revealed that LM harboured a higher proportion of CD8 + T cells, CD4 + T cells, NK cells, NKT cells, and B cells exhibiting a stress-like phenotype compared to PL. RGS5 + pericytes may play a role in the stress-like phenotype observed in immune cells within LM. MCs in PL (PL_MCs) and LM (LM_MCs) exhibit distinct activation of tumor-associated signaling pathways. Notably, COLEC11 + matrix cancer-associated fibroblasts (COLEC11_mCAFs) were found to be significantly associated with LM_MCs. Cell communication analysis unveiled potential targetable receptor-ligand interactions between COLEC11_mCAFs and LM_MCs. Multidimensional validation confirmed the prominence of the characteristic stress-like phenotypes, including HSPA6_CD8_Tstr, HSPA6_NK, and COLEC11_mCAFs in LM. Moreover, a higher abundance of COLEC11_mCAFs correlated with poorer survival rates in the neuroendocrine tumor patient cohort. Conclusion Overall, our study provides the first single-cell analysis of the cellular and molecular differences between PL and LM in CRNELM patients. We identified distinct cell subsets and receptor-ligand interactions that may drive TME discrepancies and support metastatic tumor growth. These insights highlight potential therapeutic targets and inform strategies for better managing CRNELM patients.

Abstract Background The disease impact of breast cancer is to view the couple as a whole, breast cancer is a disease shared by the couple. Cancer coping has evolved from an individual perspective to a dyadic coping perspective for couples. The purpose of this study was to identify and describe the dyadic coping categories of couples with breast cancer and to analyze the relationship between dyadic coping categories and post-traumatic growth (PTG) in couples with breast cancer. Method In this study, breast cancer patients and their spouses were selected as the study population from several tertiary hospitals in Jinzhou City using convenience sampling method in 2023. A general information questionnaire, Dyadic Coping Inventory (DCI), and Post-traumatic Growth Inventory (PTGI) were used to survey 254 couples with breast cancer. Latent profile analysis (LPA) was performed using Mplus (version 8.3). SPSS 26.0 was used for data entry, and data were analyzed using one-way analysis of variance and multifactor logistic regression. Significance level α = 0.05. Result The study examines the influence of various factors such as educational attainment, age, income, residence, medical insurance, surgical procedure type, disease stage, and breast cancer recurrence on patients' coping strategies. Multiple logistic regression analysis showed that education level, age at marriage, place of residence, form of health care coverage, stage of the disease, and whether or not the disease recurred were significant predictors of each indicator (P

Abstract Reducing interface nonradiative recombination is important for realizing highly efficient perovskite solar cells. In this work, we develop a synergistic bimolecular interlayer (SBI) strategy via 4-methoxyphenylphosphonic acid (MPA) and 2-phenylethylammonium iodide (PEAI) to functionalize the perovskite interface. MPA induces an in-situ chemical reaction at the perovskite surface via forming strong P-O-Pb covalent bonds that diminish the surface defect density and upshift the surface Fermi level. PEAI further creates an additional negative surface dipole so that a more n-type perovskite surface is constructed, which enhances electron extraction at the top interface. With this cooperative surface treatment, we greatly minimize interface nonradiative recombination through both enhanced defect passivation and improved energetics. The resulting p-i-n device achieves a stabilized power conversion efficiency of 25.53% and one of the smallest nonradiative recombination induced V oc loss of only 59 mV reported to date. We also obtain a certified efficiency of 25.05%. This work sheds light on the synergistic interface engineering for further improvement of perovskite solar cells.

BackgroundEpithelioid hemangioendothelioma (EHE), is an uncommon, intermediate-grade malignant vascular tumor that can manifest in diverse organs, including the liver, lungs, and bones. Given its unique malignancy profile and rarity, there lacks a consensus on a standardized treatment protocol for EHE, particularly for hepatic epithelioid hemangioendothelioma (HEHE). This study aims to elucidate factors influencing the clinical prognosis of EHE by analyzing data from the SEER database, complemented with insights from a departmental cohort of 9 HEHE cases. Through this, we hope to shed light on potential clinical outcomes and therapeutic strategies for HEHE.MethodsUsing SEER data from 22 registries, we analyzed 313 liver cancer patients with ICD-O-3 9130 and 9133 histology. Twelve variables were examined using Cox regression and mlr3 machine learning. Significant variables were identified and compared. Clinical data, imaging characteristics, and treatment methods of nine patients from our cohort were also presented.ResultIn univariate and multivariate Cox regression analyses, Age, Sex, Year of diagnosis, Surgery of primary site, Chemotherapy, and Median household income were closely related to survival outcomes. Among the ten survival-related machine learning models, CoxPH, Flexible, Mboost, and Gamboost stood out based on Area Under the Curve(AUC), Decision Curve Analysis(DCA), and Calibration Curve Metrics. In the feature importance analysis of these four selected models, Age and Surgery of primary site were consistently identified as the most critical factors influencing prognosis. Additionally, the clinical data of nine patients from our cohort not only demonstrated unique imaging characteristics of HEHE but also underscored the importance of surgical intervention.ConclusionFor patients with resectable HEHE, surgical treatment is currently a highly important therapeutic approach.

Hepatocellular carcinoma (HCC) is a common malignancy in China, with high recurrence rate and low resection rate among patients first diagnosed. Preoperative treatments including neoadjuvant and conversion therapy have the potential to overcome these challenges. In December 2021, Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma was published. With the emersion of new evidence regarding the neoadjuvant and conversion therapies for HCC, the cooperative group brought together multidisciplinary researchers and scholars with experience in related fields to update the new edition (2023 Edition) for reference in China, including principle of the treatment strategies, the potential populations selection, treatment methods, multi-disciplinary team (MDT) and future research for preoperative treatments. The new consensus aims to provide guidance for clinical application. Through the use of neoadjuvant therapy and conversion therapy, we can enhance the resection rate and reduce the recurrence of intermediate-to-advanced HCC patients, thereby improving survival outcomes.

Abstract Background The objective of this study was to determine the role and regulatory mechanism of miR-380 in cholangiocarcinoma. Methods The TargetScan database and a dual-luciferase reporter assay system were used to determine if LIS1 was a target gene of miR-380. The Cell Counting Kit 8 assay, flow cytometry, and Transwell assay were used to detect the effects of miR-380 and LIS1 on the proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. Western blotting was used to determine the effect of miR-380 on MMP-2/p-AKT. Immunohistochemistry detected the regulatory effect of miR-380 on the expression of MMP-2/p-AKT/LIS1. Results Expression of miR-380 in cholangiocarcinoma was decreased but expression of LIS1 was increased. LIS1 was confirmed to be a target gene of miR-380. Transfection with miR-380 mimics inhibited the proliferation, S-phase arrest, and invasion of HCCC-9810/HuCCT1/QBC939 cells, and LIS1 reversed these inhibitory effects. miR-380 inhibitor promoted proliferation, S-phase ratio, and invasiveness of HCCC-9810/HuCCT1/QBC939 cells. si-LIS1 salvaged the promotive effect of miR-380 inhibitor. Overexpression of miR-380 inhibited expression of MMP-2/p-AKT/LIS1, but miR-380 inhibitor promoted their expression. Conclusion An imbalance of miR-380 expression is closely related to cholangiocarcinoma, and overexpression of miR-380 inhibits the expression of MMP-2/p-AKT by directly targeting LIS1.

Interfacial differences between the Hf0.5Zr0.5O2 (HZO) and the top/bottom electrodes caused by the process sequence could lead to the imprint effect of the TiN/HZO/TiN ferroelectric capacitor, which leads to serious reliability problems. In this article, a method of introducing a HfO2 protective layer is proposed to inhibit the imprint effect of the TiN/HZO/TiN ferroelectric capacitor. By introducing the HfO2 protective layer, the leakage current at the positive electric field is reduced by three orders of magnitude, the asymmetry of the coercive field is reduced from 1.5 to 0.1 MV/cm, and the endurance is improved by two orders of magnitude with no degradation in retention. The proposed method provides a feasible strategy to inhibit the imprint effect of TiN/HZO/TiN ferroelectric capacitors and is more compatible with complementary metal–oxide–semiconductor processes.

Abstract Background Social media has become an indispensable part of contemporary young people's lives, and the influence of social media on college students' eating and other health-related behaviors has become increasingly prominent. However, there is no assessment tool to determine the effects of social media on Chinese college students' eating behavior. This study aims to translate the Scale of Effects of Social Media on Eating Behaviour (SESMEB) into Chinese. Its applicability to Chinese college students was examined through reliability and validity indexes, and the influencing factors of SESMEB were explored. Methods The questionnaire survey included 2374 Chinese college students. The Brislin translation model was used to translate the original scale into Chinese. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to test the construct validity of the scale, and the content validity of the scale was assessed through the content validity index. The internal consistency of the scale was assessed by calculating Cronbach's alpha coefficient, McDonald's Omega coefficient, split-half reliability, and test–retest reliability. Multiple stepwise linear regression analysis was performed to identify potential influences on the effects of social media on eating behavior. Results EFA supported the one-factor structure, and the factor loadings of each item on this dimension were higher than 0.40. CFA showed good model fitness indexes. The content validity index of the scale was 0.94. The Cronbach's alpha coefficient and McDonald's Omega coefficient for the scale were 0.964, the split-half reliability coefficient was 0.953, and the test–retest reliability was 0.849. Gender, education, major, frequency of social media use, online sexual objectification experiences, fear of negative evaluations, and physical appearance perfectionism explained 73.8% of the variance in the effects of social media on eating behavior. Conclusions The Chinese version of the SESMEB has good psychometric properties and is a valid measurement tool for assessing the effects of social media on college students' eating behavior. Subjects who were female, highly educated, non-medical, had frequent social media use, online sexual objectification experiences, fear of negative evaluations, and physical appearance perfectionism used social media to have a higher impact on eating behavior.

Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases. However, a lack of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of these strategies. This review presents the viewpoints from an international conference consisting of several expert working groups. The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature, evaluating the evidence on which management decisions were based, developing internationally acceptable recommendations for clinical practice, and making recommendations for clinical and research endeavors. The review for each question will be followed by recommendations from the panel.

Abstract Background To explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases. Methods A total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden’s index. Patients were divided into the CLR 0.1). Compared with patients with CLR

More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.

Background: This case report presents two clinical cases of metastatic refractory gastrointestinal stromal tumor (GIST) with treatment history of 6–14 years. The follow-up treatment of both cases comprised ripretinib dose escalation and its combination with other tyrosine kinase inhibitors (TKIs). To the best of our knowledge, this is the first report that explored ripretinib combination therapy in the late-line treatment of GISTs.Case description: Case-1 represents a 57-year-old female patient who underwent surgical resection for retroperitoneal GIST in 2008. After tumor recurrence in 2009, imatinib was started with complete response for 8 years. Imatinib was followed by sunitinib and regorafenib treatment. In March 2021, due to progressive disease (PD), the patient started ripretinib (150 mg QD) and achieved partial response (PR). Six months later, the patient showed PD. Subsequently, ripretinib dose was increased (150 mg BID) followed by ripretinib (100 mg QD) and imatinib (200 mg QD) combination. CT performed in February 2022 revealed stable lesions with internal visible necrosis. Combination therapy achieved stable disease (SD) for 7 months. On further follow-up in July 2022, the patient showed PD and died in September 2022.Case-2: represents a 73-year-old female patient diagnosed with unresectable duodenal GIST with liver, lung, and lymph node metastases in 2016. After treatment with imatinib, followed by sunitinib, regorafenib, and imatinib rechallenge, ripretinib (150 mg QD) was administered in May 2021, and SD was achieved. Ripretinib dose was increased (200 mg QD) due to PD in December 2021. The tumor showed heterogeneous manifestations, with overall size increase and regression in right posterior lobe. In February 2022, ripretinib (150 mg) plus sunitinib (25 mg) QD was commenced. On follow-up in April 2022, the patient showed slightly improved symptoms with stable hematologic parameters. Combination therapy achieved SD for 5 months and the patient showed PD in July 2022 and discontinued the treatment later. The patient was in poor general condition and was receiving nutritional therapy until last follow-up in October 2022.Conclusion: This case report provides evidence that combination therapy of ripretinib with other TKIs could be an effective late-line treatment option for refractory GIST patients.

The interface difference between HZO and the upper and lower electrodes induced by the sequence of the process flow could lead to the general asymmetry in the structure and performance of metal-ferroelectric-metal (MFM) capacitors, which may cause serious reliability problems. In this letter, we have exploited a special high pressure annealing (HPA) process, called alcohol-thermal method (ATM), to improve the symmetry of TiN/HZO/TiN capacitors. The original control device exhibits asymmetric leakage current and coercive fields. This has been significantly improved by the ATM, which was performed at temperature of 240°C and atmospheric pressure of 70 atm, in C2H6O ambient. The enhancement of ferroelectricity can be attributed to the reduction of the thickness and defects of the non-ferroelectric layers in the device. The improvement of symmetry leads to the operation ability under low voltages, which is critical to the endurance of devices. Under the electric field of 2.4 MV/cm with 10 MHz frequency, the lifetime of the TiN/ HZO/TiN device after HPA process was measured up to 1010 cycles. This work provides an effective way to improve symmetry and ferroelectricity of hafnium-based ferroelectric capacitors.

Abstract Aims and objectives Acute-on-chronic hepatitis B liver failure (ACHBLF) is a critical clinical syndrome with a high short-term mortality evolved from chronic hepatitis B (CHB)-related liver disease. Prediction of mortality risk and early intervention can improve the prognosis of patients. This study aimed to develop and validate the nomogram for short-time mortality estimation in ACHBLF patients defined according to Asian Pacific Association for the Study of the Liver (APASL). Methods A study of 105 ACHBLF patients with 90-day follow up was performed to develop the nomogram. Patients were randomly assigned to derivation cohort (n = 75) and validation cohort (n = 35) according to 7:3. Concordance index (C-index), calibration curve and decision curve analysis (DCA) were used to evaluate the nomogram. We also compared the nomogram with APASL ACLF research consortium (AARC) score, model for end-stage liver disease (MELD) score, MELD with serum sodium (MELD-Na) score and albumin-bilirubin (ALBI) score. The nomogram was validated using an external cohort including 40 patients. Results The 28-day and 90-day mortality of 105 patients were respectively 49.52% and 55.24%. Albumin (ALB), international normalized ratio (INR) and estimated glomerular filtration rate (eGFR) were independent predictors for 28-day mortality; INR and eGFR were independent predictors for 90-day mortality. C-index of Nomogram-1 for 28-day mortality and Nomogram-2 for 90-day mortality were respectively 0.82 and 0.81. Calibration curve and Hosmer–Lemeshow test (Nomogram-1, 0.323; Nomogram-2, 0.231) showed optimal agreement between observed and predicted death. Areas under receiver operator characteristic curve(AUROC) of Nomogram-1(0.772) and Nomogram-2(0.771) were larger compared with AARC, MELD, MELD-Na and ALBI score. The results were well estimated in the external validation cohort. Conclusions This study highlighted the predictive value of eGFR, and the nomogram based on INR and eGFR could effectively estimate individualized risk for short-term mortality of ACHBLF patients defined according to APASL.

Perioperative immune function, postoperative cognitive function and prognosis are momentous issues for patients undergoing digestive tract cancer surgery. Studies have investigated the efficacy of dexmedetomidine (DEX) administration on these issues, but the results are inconsistent. Therefore, this meta-analysis aimed to summarize all the existing evidence and draw a conclusion more accurately on these associations. Trials were located through electronic searches of the PubMed, Embase, the Cochrane Library and Web of Science databases sources (from the establishment date of databases to April 2022). Bibliographies of the retrieved articles were checked. A total of 17 RCTs involving 1619 patients were included. The results showed that DEX decreased the level of C-reactive protein (SMD = -4.26, 95%CI: -6.16, -2.36), TNF-α (SMD = -4.22, 95%CI: -5.91, -2.54) and IL-6 (SMD = -2.71, 95%CI: -4.46, -0.97), and increased the level of IL-10 (SMD = 1.74, 95%CI: 0.25, 3.24). DEX also increased CD4+ T cells (SMD = 0.55, 95%CI: 0.29, 0.82) and CD4+/CD8+ ratio (SMD = 0.62, 95%CI: 0.24, 1.01). Thus, DEX was associated with alleviation of postoperative systemic inflammatory response and immune dysfunction. Furthermore, DEX increased mini-mental state examination scores at 12h (SMD = 1.10, 95%CI: 0.74,1.45), 24h (SMD = 0.85, 95%CI: 0.59, 1.11), 48h (SMD = 0.89, 95%CI: 0.50, 1.28) and 72h (SMD = 0.75, 95%CI: 0.38, 1.11) after surgery. DEX decreased the occurrence of postoperative cognitive dysfunction (POCD) at 24h (OR = 0.22, 95%CI: 0.11, 0.46) and 72h (OR = 0.39, 95%CI: 0.22, 0.68) after surgery. DEX decreased first flatus time (SMD = -1.55, 95%CI: -2.82, -0.27) and hospital stay (SMD = -1.23, 95%CI: -1.88, -0.59). Therefore, based on perioperative immune dysfunction alleviation, DEX attenuated POCD and potential neuroinflammation, improved postoperative recovery and clinical prognosis of patients undergoing digest tract cancer surgery. Further studies are necessary to elucidate the clinical application of DEX from an immunological perspective.

Abstract Background Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with intrahepatic cholangiocarcinoma (ICC) after radical resection. Method The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV (SCC), classified into SCC = 0, 1 and 2 group. Kaplan–Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. Results Kaplan–Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (p = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (p 40.2 fl (HR = 0.446, 95% CI: 0.262–0.760, p = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230–0.783, p = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133–0.549, p

The non-ideal characteristics at the interfaces of anti-ferroelectric (AFE) film and electrodes will greatly affect the potential performance in the way to embedded dynamic random-access memory applications. In this paper, we have proposed a high-performance AFE TiN/HfxZr1−xO2/TiN capacitor fabricated by fully atomic layer deposition grown and alcohol-thermal high-pressure annealing methods that have been employed to avoid exposure to the ambient atmosphere and cure the interface defects induced by the inevitable oxidization of electrodes. Due to the high improvement of the interface quality, the capacitors based on ultra-thin (∼6 nm) AFE film show competitive memory performances, such as low operating voltage (−0.6/1.8 V), high speed (10 ns), long retention time (103 s), and high endurance (1012). The final benchmark demonstrates that the proposed AFE TiN/HfxZr1−xO2/TiN capacitor is a promising candidate toward the next generation high-speed and high-density embedded memory.

Abstract Background Neoadjuvant chemotherapy (NAC) has been widely performed in the treatment of colorectal cancer liver metastasis (CRLM) patients, but the optimal timing of surgery after NAC is unclear. The aim of this study was to investigate the optimal timing of surgery. Methods From December 2010 to May 2018, 101 consecutive patients who received NAC followed by liver resection for CRLM were included in this study. The main outcome parameters were pathological response, progression‐free survival (PFS), and overall survival (OS). The effect of time to surgery (TTS) on patient outcomes, defined as a high TTS and a low TTS according to an X‐tile analysis, was investigated. To adjust for potential selection bias, propensity score matching at 1:2 was performed with two high TTS patients matched to one low TTS patient. Kaplan‐Meier curves, logistic regression analyses, and Cox regression models were used for the data analysis. Results The optimal cut‐off value for the TTS was 5 weeks by X‐tile analysis. The patients in this study were divided into low (≤5 weeks, n = 27) and high (>5 weeks, n = 74) TTS groups. Patients with a high TTS were more likely to have an unfavorable pathological response (75.7% vs 48.1%, P = .008). In multivariate analysis, a low TTS significantly predicted a better pathological response (OR = 3.397, 95% CI: 1.116‐10.344, P = .031). Compared to patients with a high TTS, patients with a low TTS had significantly better PFS (P 5 weeks was an independent predictor of decreased PFS (HR = 2.041, 95% CI: 1.152‐3.616, P = .014) but not OS. After propensity matching, the patients with a low TTS had significantly better PFS (P 5 weeks was an independent predictor of decreased PFS (HR = 3.031, 95% CI: 1.494‐6.149, P = .002) but not OS. Conclusion The longer TTS after the completion of NAC may be disadvantageous for a favorable pathological response and long‐term PFS. These results should be validated prospectively in a randomized trial.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small molecular weight tyrosine kinase-inhibitor (SMW TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors (ICIs) for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists，radiologists，pathologists, orthopedic surgeons, traditional Chinese medicine physicians and interventional radiologists have reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

ObjectiveTo investigate the impact of postoperative infectious complications (POI) on the long-term outcomes of patients with colorectal cancer liver metastasis (CRLM) after simultaneous resection of colorectal cancer and liver metastases.MethodsFour hundred seventy-nine CRLM patients receiving simultaneous resection between February 2010 and February 2018 at our hospital were enrolled. A 1:3 propensity score matching analysis (PSM) analysis was performed to balance covariates and avoid selection bias. After PSM, 90 patients were distributed to the POI group, and 233 patients were distributed to the no POI group. A log-rank test was performed to compare the progression-free survival (PFS) and overall survival (OS) data. A multivariate Cox regression model was employed to identify prognostic factors influencing OS and PFS. A value of two-sided P

OBJECTIVES: To investigate the predictive value of the pre-operative D-dimer and gamma-glutamyltranspeptidase (GGT) for the prognosis in colorectal liver metastases (CRLM) patients after hepatic resection. METHODS: Two hundred and ninety-two patients between December 2008 and December 2016 and 101 patients at our center from January 2017 to December 2018 were selected as a training set and validation set, respectively. The combination of the pre-operative D-dimer and GGT status (CPDG score) was scored as follows: elevated D-dimer levels with elevated GGT levels was allocated a score of 2, decreased D-dimer levels with decreased GGT levels was allocated a score of 0, and all other combinations were allocated a score of 1. In the training set, a logistic regression was applied to explore potential predictors of major postoperative complications. A Cox proportional hazards analysis was used to analyze survival. We further verified our findings in the validation set. RESULTS: Major complications occurred in 43 (14.7%) and 25 (24.8%) patients in the training set and validation set, respectively. In the training set, multivariate analysis showed that elevated GGT levels and elevated D-dimer levels independently predicted major complications respectively. In the multivariate analyses, elevated pre-operative D-dimer levels remained independently associated with decreased overall survival (OS) (hazard ratio [HR] = 1.751, 95% confidence interval [CI]: 1.139-2.691, P = .01). The CPDG score was an independent prognostic factor for major complications and OS in the multivariate analyses. The predictive ability of the CPDG score was higher than either factor alone. A Kaplan-Meier survival analysis showed that compared with patients with CPDG score = 1 or CPDG score = 0, patients with a CPDG score = 2 had worsened OS. Furthermore, for OS comparisons, the differences between any two groups were significant. In the validation set, elevated GGT and D-dimer were also suggested to predict worse progression-free survival (PFS) and to be independently associated with major complications. CONCLUSIONS: The pre-operative D-dimer levels, GGT levels and CPDG score are reliable biomarkers to predict post-operative major complications or survival in CRLM patients after hepatic resection, which make it useful for CRLM patients in guiding surveillance approaches and prognosis assessments.

Pancreatic squamous cell carcinoma (SCC) is a rare primary pancreatic malignancy with a poor prognosis. The median overall survival (OS) for metastatic setting is only 4 months and the optimal management remains poorly defined. In the present study, we report a 52-year-old female patient with stage IV primary SCC of the pancreas harboring a deleteous BRCA2 somatic mutation. After 10 cycles of chemotherapy of cisplatin combined with nanoparticle albumin-bound paclitaxel, metastatic lesions in the liver and lymph nodes achieved radiographic complete responses and pancreatic lesion shrank from 5.7 to 1.5 cm in diameter. The patient subsequently underwent a posterior radical antegrade modular pancreatosplenectomy with R0 resection and residual liver lesions were also resected. After 3 months, a tumor relapsed in the liver. She was then treated with olaparib combined with pembrolizumab and achieved stable disease on the liver lesion. The patient eventually died from cerebral hemorrhage with a long OS of 21 months. Our case demonstrated a favorable clinical activity and survival advantage of the combined cisplatin and nanoparticle albumin-bound paclitaxel, which might serve as a therapeutic option for the patient with BRCA-mutant pancreatic SCC.

Background: Post-surgical recurrence of the metastatic colorectal cancer (mCRC) remains a challenge, even with adjuvant therapy. Moreover, patients show variable outcomes. Here, we set to identify gene models based on the perspectives of intrinsic cell activities and extrinsic immune microenvironment to predict the recurrence of mCRC and guide the adjuvant therapy.Methods: An RNA-based gene expression analysis of CRC samples (total = 998, including mCRCs = 344, non-mCRCs = 654) was performed. A metastasis-evaluation model (MEM) for mCRCs was developed using the Cox survival model based on the prognostic differentially expressed genes between mCRCs and non-mCRCs. This model separated the mCRC samples into high- and low-recurrence risk clusters that were tested using machine learning to predict recurrence. Further, an immune prognostic model (IPM) was built using the COX survival model with the prognostic differentially expressed immune-related genes between the two MEM risk clusters. The ability of MEM and IPM to predict prognosis was analyzed and validated. Moreover, the IPM was utilized to evaluate its relationship with the immune microenvironment and response to immuno-/chemotherapy. Finally, the dysregulation cause of IPM three genes was analyzed in bioinformatics.Results: A high post-operative recurrence risk was observed owing to the downregulation of the immune response, which was influenced by MEM genes (BAMBI, F13A1, LCN2) and their related IPM genes (SLIT2, CDKN2A, CLU). The MEM and IPM were developed and validated through mCRC samples to differentiate between low- and high-recurrence risk in a real-world cohort. The functional enrichment analysis suggested pathways related to immune response and immune system diseases as the major functional pathways related to the IPM genes. The IPM high-risk group (IPM-high) showed higher fractions of regulatory T cells (Tregs) and smaller fractions of resting memory CD4+ T cells than the IPM-low group. Moreover, the stroma and immune cells in the IPM-high samples were scant. Further, the IPM-high group showed downregulation of MHC class II molecules. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and GDSC analysis suggested the IPM-low as a promising responder to anti-CTLA-4 therapy and the common FDA-targeted drugs, while the IPM-high was non-responsive to these treatments. However, treatment using anti-CDKN2A agents, along with the activation of major histocompatibility complex (MHC) class-II response might sensitize this refractory mCRC subgroup. The dysfunction of MEIS1 might be the reason for the dysregulation of IPM genes.Conclusions: The IPM could identify subgroups of mCRC with a distinct risk of recurrence and stratify the patients sensitive to immuno-/chemotherapy. Further, for the first time, our study highlights the importance of MHC class-II molecules in the treatment of mCRCs using immunotherapy.

Introduction: Prognosis prediction is essential to improve therapeutic strategies and to achieve better clinical outcomes in colorectal cancer (CRC) patients. Radiomics based on high-throughput mining of quantitative medical imaging is an emerging field in recent years. However, the relationship among prognosis, radiomics features, and gene expression remains unknown.Methods: We retrospectively analyzed 141 patients (from study 1) diagnosed with CRC from February 2018 to October 2019 and randomly divided them into training (N = 99) and testing (N = 42) cohorts. Radiomics features in venous phase image were extracted from preoperative computed tomography (CT) images. Gene expression was detected by RNA-sequencing on tumor tissues. The least absolute shrinkage and selection operator (LASSO) regression model was used for selecting imaging features and building the radiomics model. A total of 45 CRC patients (study 2) with immunohistochemical (IHC) staining of CXCL8 diagnosed with CRC from January 2014 to October 2018 were included in the independent testing cohort. A clinical model was validated for prognosis prediction in prognostic testing cohort (163 CRC patients from 2014 to 2018, study 3). We performed a combined radiomics model that was composed of radiomics score, tumor stage, and CXCL8-derived radiomics model to make comparison with the clinical model.Results: In our study, we identified the CXCL8 as a hub gene in affecting prognosis, which is mainly through regulating cytokine–cytokine receptor interaction and neutrophil migration pathway. The radiomics model incorporated 12 radiomics features screened by LASSO according to CXCL8 expression in the training cohort and showed good performance in testing and IHC testing cohorts. Finally, the CXCL8-derived radiomics model combined with tumor stage performed high ability in predicting the prognosis of CRC patients in the prognostic testing cohort, with an area under the curve (AUC) of 0.774 [95% confidence interval (CI): 0.674–0.874]. Kaplan–Meier analysis of the overall survival probability in CRC patients stratified by combined model revealed that high-risk patients have a poor prognosis compared with low-risk patients (Log-rank P < 0.0001).Conclusion: We demonstrated that the radiomics model reflected by CXCL8 combined with tumor stage information is a reliable approach to predict the prognosis in CRC patients and has a potential ability in assisting clinical decision-making.