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To retrospectively compare the survival outcomes of thermal ablation plus chemotherapy to those of chemotherapy alone in patients with unresectable intrahepatic cholangiocarcinoma (ICC). 189 patients with unresectable ICC who received thermal ablation plus chemotherapy or chemotherapy alone as the initial treatment were identified. To avoid potential bias, 1:1 matching between groups was performed through propensity score matching. Overall survival (OS) was the primary endpoint. Clinical and tumor factors related to OS were analyzed through univariate and multivariate analyses. Of the enrolled patients, 55 received ablation plus chemotherapy, and 134 received chemotherapy alone. The median OS was 16.267 months for patients treated with combined therapy and 6.067 months for patients treated with chemotherapy alone (p = 0.000). The benefit of ablation plus chemotherapy was also preserved in the matched cohort, with a median OS of 15.233 months in the combined treatment group and 7.967 months in the chemotherapy group (p = 0.009). Univariate and multivariate analyses indicated that the type of treatment was an independent factor of OS (p < 0.05). The combination of thermal ablation and systemic chemotherapy provides an opportunity to improve the prognosis of patients with unresectable ICC. [ABSTRACT FROM AUTHOR]

Objectives: To retrospectively assess the efficacy of combined ablation-chemotherapy in comparison to that of chemotherapy alone in patients with liver metastasized pancreatic ductal adenocarcinoma (lmPDAC). Methods: In total 104 patients with hepatic oligo metastasized PDAC were identified; among them, 74 patients underwent combined thermal ablation-chemotherapy, and 30 patients underwent chemotherapy alone. Through propensity score matching, 1:1 matching of the combined ablation-chemotherapy group and chemotherapy group was achieved. The primary endpoint of this study was overall survival (OS). Clinical and tumor-related factors affecting OS were also analyzed through univariate and multivariate analyses using the Cox risk model. Results: For patients treated with combined ablation-chemotherapy, the median OS was 10.77 months, while it was 5.77 months for patients treated with chemotherapy alone (P = 0.011). The survival benefit for patients treated with combined ablation-chemotherapy was still preserved in the matched cohort, with a median OS of 8.17 months compared to 5.77 months in the chemotherapy group. Univariate and multivariate analyses in the matched population also showed treatment with combined ablation-chemotherapy was an independent prognostic factor (P < 0.05). Conclusions: For patients with liver metastases from pancreatic cancer, the combined use of thermal ablation and systemic chemotherapy offers a chance for a better survival outcome. [ABSTRACT FROM AUTHOR]

Purpose: Liver metastasis is a common phenomenon in breast cancer patients. Hepatic lesions detected in breast cancer patients may be easily misdiagnosed as metastatic sites, rather than being treated as primary foci. This descriptive study aims to investigate the clinicopathological characteristics of second primary hepatocellular carcinoma in breast cancer patients and to infer in which circumstances liver biopsy is needed. Methods: Eighty-one consecutive breast cancer patients with hepatic lesions admitted to our department were retrospectively studied and analyzed from January 2009 to March 2014 according to Warren and Gates’ criteria for second primary cancers. Results: Second primary hepatocellular carcinoma was observed in sixteen of seventy eight patients with breast cancer. There was a significant difference in HBV status between the second HCC group and liver metastases group (P<0.0001). There was no significant difference in age (P = 0.2254) and family history (P = 0.1160) between second primary HCC and metastases group. Two of these patients had synchronous second primary hepatocellular carcinoma and the remaining fourteen patients had metachronous second primary HCC. All sixteen patients were infected with hepatitis, including hepatitis virus B and C, or resolved HBV infection. Conclusions: Breast cancer patients with either HBV infection or resolved HBV infection, regardless of an elevated AFP level, may receive liver biopsy to avoid unnecessary and inappropriate treatments for metastasis. Awareness of second primary HCC in breast cancer patients needs to be emphasized. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) can be diagnosed by noninvasive approaches with serum α-fetoprotein (AFP) levels >200 ng/ml and/or a radiological imaging study of tumor mass >2 cm in patients with chronic liver disease. Percutaneous fine needle aspiration (FNA) under ultrasound (US) guidance has a diagnostic specificity of 95% and is superior to radiological imaging studies. Aim: The aim of this study is to elucidate the effectiveness and complications of fine needle aspiration in a Chinese population with primary liver cancer and AFP levels ≤200 ng/ml. Materials and Methods: A retrospective study was conducted over a period of 28 years. This selection period included patients with a suspected diagnosis of primary liver cancer whose AFP levels were ≤200 ng/ml and who underwent US-FNA. This data was then analyzed with cytomorphological features correlating with medical history, radiological imaging, AFP, and follow-up information. Results: Of the 1,929 cases with AFP ≤200 mg/ml, 1,756 underwent FNA. Of these, 1,590 cases were determined malignant and the remaining 166 were determined benign. Further, 1,478 malignant cases were diagnosed by FNA alone, and of these, 1,138 were diagnosed as PLC. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the diagnoses were 92.96%, 100%, 100%, 59.71%, and 93.62% respectively. There was no significant difference in the sensitivity, specificity, PPV and NPV between the subgroups with tumor size<2 cm and ≥2 cm. Major complications included implantation metastasis and hemorrhage. Conclusion: Patients with PLC, especially those who present with an AFP ≤200 ng/ml, should undergo FNA. If negative results are obtained by FNA, it still could be HCC and repeated FNA procedure may be needed if highly suspicious of HCC on imaging study. The superiority of FNA in overall accuracy may outweigh its potential complications, such like hemorrhage and implantation metastasis. [ABSTRACT FROM AUTHOR]

Background: The immune checkpoint inhibitor (ICIs) therapy has been proven effective in a range of solid tumors including hepatocellular carcinoma (HCC), non-small cell lung carcinoma and metastatic melanoma. However, only a subset of approximately 20% of patients shows an objective response to anti-PD-1 therapy in HCC. Furthermore, the response to anti-PD-1 therapy is not correlated with programmed cell death 1 ligand expression in tumor tissue. Therefore, it is urgent to identify a biomarker to predict the response of anti-PD-1 therapy., Methods: This retrospective study was conducted at the Fudan University Shanghai Cancer Center from December 2019 to June 2021. The monocyte-to-lymphocyte ratio (MLR) was analyzed using a receiver operating characteristic (ROC) curve. A Cox regression model and the log-rank test were used to analyze the relationship between the MLR value and the time to progression (TTP)., Results: A total of 34 advanced HCC patients were enrolled in this study. The cut-off point for the MLR at baseline was 0.35. Univariate and multivariate Cox regression models showed that the MLR at baseline was significantly correlated with the TTP (P<0.05). Consistent results were found for disease progression. The log-rank test showed that patients in the low MLR group had a longer TTP (P=0.0027). At the time of disease progression, the median TTP in the low and high MLR groups were 33 and 18 weeks, respectively (P=0.0047)., Conclusions: The MLR can predict the response to anti-PD-1 therapy, and a high MLR is correlated with a short TTP in anti-PD-1-treated HCC patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-21-1760/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient prognosis. A cellular stress response mechanism called the unfolded protein response (UPR) has been implicated in PDAC progression. More recently, nucleobindin 1 (NUCB1), a calcium-binding protein, has been shown to control the UPR but its precise role in PDAC has not been explored. Here, we found that downregulation of NUCB1 was associated with poor prognosis in patients with PDAC. Functionally, NUCB1 overexpression suppressed pancreatic cancer cell proliferation and showed additive effects with gemcitabine (GEM) in vitro and in vivo . Moreover, by controlling ATF6 activity, NUCB1 overexpression suppressed GEM-induced UPR and autophagy. Last but not least, we uncovered METTL3-mediated m 6 A modification on NUCB1 5'UTR via the reader YTHDF2 as a mechanism for NUCB1 downregulation in PDAC. Taken together, our study revealed crucial functions of NUCB1 in suppressing proliferation and enhancing the effects of gemcitabine in pancreatic cancer cells and identified METTL3-mediated m 6 A modification as a mechanism for NUCB1 downregulation in PDAC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hua, Zhang, Sheng, Ning, Li, Shi and Liu.)

Background: Tumor mutation burden (TMB) has an important association with immunotherapy responses. TMB in the Chinese population has not been well established. Finding differences between the Chinese and Caucasian populations and elucidating the underlying biological mechanisms of high TMB might help develop more precise and effective means for TMB and immunotherapy response prediction., Methods: Chinese cancer patients fresh tissue (n=2,177), formalin-fixed, paraffin-embed (FFPE) specimens (n=3,294), and pleural fluid (n=189) were profiled using a 295- or 520-gene next-generation sequencing (NGS) panel. The association of the TMB status with a series of molecular features and biological pathways was determined using bootstrapping., Results: TMB, measured by 295- or 520-cancer-related gene panels, was correlated with whole-exome sequencing (WES) TMB based on the in silico simulation in The Cancer Genome Atlas cohort. The median TMB of our data was slightly higher than that from the Foundation Medicine Inc. (FMI) dataset. TMB was also slightly different within the same cancer type between the Chinese and Caucasian population. We discovered that the underlying pathways of TMB status varied greatly and sometimes had an opposite association with TMB across different cancer types. Moreover, we developed a 23-gene and a 16-gene signature to predict TMB prediction for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, indicating a histology-specific mechanism for driving high-TMB in lung cancer., Conclusions: TMB varies among different ethnic populations. Our findings extend the knowledge of the underlying biological mechanisms for high TMB and might be helpful for developing more precise and accessible TMB assessment panels and algorithms in more cancer types., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3807). Dr. SC, Dr. YSZ, Dr. HHZ, Dr. JY and Dr. TH report that they are employees of Burning Rock Biotech. The other authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: This study is implemented to probe into the function of lncRNA SBF2-AS1 as a competing endogenous RNA (ceRNA) to sponge microRNA-142-3p (miR-142-3p) in modulating TWF1 expression in the gemcitabine resistance of pancreatic cancer., Results: LncRNA SBF2-AS1 was highly expressed in pancreatic cancer tissues and cells. SBF2-AS1 was found to be associated with gemcitabine resistance in pancreatic cancer. Knock-down of SBF2-AS1 inhibited proliferation, epithelial-mesenchymal transition, while promoting apoptosis of gemcitabine resistant pancreatic cancer cells. SBF2-AS1 inhibited the expression of TWF1 by competitively binding with miR-142-3p in pancreatic cancer., Conclusion: Our study demonstrates that knock-down of SBF2-AS1 inhibits the expression of TWF1 by competitively binding with miR-142-3p to induce gemcitabine resistance in pancreatic cancer., Methods: Expression of SBF2-AS1 was tested in pancreatic cancer tissues and cells. Construction of AsPC-1/GEM and PANC-1/GEM cells with low expression of SBF2-AS1 was performed to determine the biological behaviors of drug-resistant cells. AsPC-1 and PANC-1 cells expressing SBF2-AS1 and/or miR-142-3p were constructed and treated with different concentrations of gemcitabine to detect the sensitivity of the cells to gemcitabine. The binding relationship between SBF2-AS1 and miR-142-3p and between miR-142-3p and TWF1 were determined.

Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. Recent years have witnessed the progress in uncovering the importance of HSFs in cancer cell oncogenesis, progression and metastasis. However, their roles in hepatocellular carcinoma (HCC) proliferation and the underlying mechanism have seldom been discussed. The present study aims to uncover the two important HSFs members HSF1 and HSF2 in hepatocellular carcinoma (HCC). By using the Cancer Genome Atlas (TCGA) dataset analysis, we investigated the prognosis value of HSF1 and HSF2 in HCC and identified HSF2 as a prediction factor of overall survival of HCC. In vitro cell line studies demonstrated that silencing HSF2 expression could decrease the proliferation in HCC cells. In depth mechanism analysis demonstrated that HSF2 promoted cell proliferation via positive regulation of aerobic glycolysis, and HSF2 interacted with euchromatic histone lysine methyltransferase 2 (EHMT2) to epigenetically silence fructose-bisphosphatase 1 (FBP1), which is a tumor suppressor and negative regulator of aerobic glycolysis in HCC. HSF2 expression indicated unfavorable prognosis of HCC patients and it could regulate aerobic glycolysis by suppression of FBP1 to support uncontrolled proliferation of HCC cells., Competing Interests: None.

Background: Chemotherapy-induced nausea and vomiting adversely affects the quality of life of patients who receive chemotherapy via intravenous infusion or transcatheter arterial chemoembolization (TACE). This study aimed to investigate the clinical effects of transcutaneous electrical acupoint stimulation (TEAS) on nausea and vomiting after TACE., Methods: A total of 142 patients who received TACE with cisplatin for primary or metastatic liver cancer were assigned to the active-acupuncture (n = 72) or placebo-acupuncture (n = 70) groups using a covariate-adaptive randomization at a ratio of 1:1. The acupoints Hegu (LI4), Neiguan (P6), and Zusanli (ST36) were stimulated twice daily for 6 days. The effects of TEAS on nausea and vomiting were assessed by using occurrence rate and severity of these symptoms. Anorexia scale and M. D. Anderson Symptom Inventory (MDASI) scores were secondary endpoints and were used to assess the effect of TEAS on patient appetite and quality of life. The safety of the treatments was also monitored., Results: Between the two groups, the differences in occurrence rates and severities of nausea and vomiting after TACE were not significant (all P > 0.05). From the second day after TACE, anorexia scores were significantly lower in the active-acupuncture group than in the placebo-acupuncture group and continued to decrease over time with treatment (all P values less than 0.01). On days 0, 1, and 2, the mean MDASI scores for the active-acupuncture group were slightly lower than those for the placebo-acupuncture group, but the differences were not statistically significant (all P > 0.05). No significant differences were found between the two groups in the occurrence rate of any adverse event (P > 0.05)., Conclusion: TEAS appears to be a safe and effective therapy to relieve patients' gastrointestinal discomfort after chemotherapy. Trial registration NCT01895010. Registered 21 June 2013.

Objective: To retrospectively evaluate possible impact factors of HIFU treatment outcome for unresectable pancreatic cancer patients., Patients and Methods: A total of 689 patients with unresectable pancreatic cancer were recruited in our center from December 30, 2007 to January 30, 2015. 436 patients with unresectable pancreatic cancers received HIFU treatment; the other 253 patients received non-HIFU treatment. Among these 436 patients, 345 patients received a one-time HIFU treatment, 91 patients received HIFU treatment from 2 to 5 times in the same pancreatic mass; 89 patients received HIFU treatment alone; 347 patients received HIFU-based combined therapies. Complications and overall survivals (OS) data in each group were collected., Results: The median overall survivals (mOS) in HIFU group and non-HIFU group were 7.1 vs. 5 months (P=0.005): 9.3 vs. 7.3 months (P=0.202) for patients with stage II disease, 8.3 vs. 7.3 months (P=0.783) for patients with stage III disease, and 6.4 vs. 4.2 months (P<0.0001) for patients with stage IV disease, respectively. Furthermore, there was a significant difference between repeated HIFU and one-time HIFU (mOS: 8.6 vs. 6.8 months, P=0.011). Time of HIFU treatment (P=0.0027), chemotherapy (P<0.0001), radiotherapy (P=0.0006), regional intra-arterial chemotherapy (RIAC) (P<0.0001), and stage (P<0.0001) were independent prognostic factors for the patients who received HIFU treatment. Cox analysis on the relative risk of prognostic factors showed that repeated HIFU vs. one-time HIFU (HR=0.729: 95% CI=0.576-0.924), chemotherapy vs. non-chemotherapy (HR=0.664: 95% CI=0.576-0.766), radiotherapy vs. non-radiotherapy (HR=0.580: 95% CI=0.427-0.789), RIAC vs. non-RIAC (HR=0.737: 95% CI=0.648-0.837), and stage (HR=1.386, 95% CI=1.187-1.619) were associated with significantly inferior survival. Overall, adverse events occurred in 23.2% (101/436) in the HIFU group, which included increase of serum or urinary amylase levels, incomplete intestinal obstruction, mild fever, etc. There were no severe adverse events such as skin burns or GI perforation related to HIFU therapy in any of the patients treated., Conclusion: This retrospective analysis revealed that the use of a multimodal treatment approach (the combined therapy of HIFU, RIAC, and chemotherapy, with or without radiotherapy) could improve survival of patients with unresectable pancreatic cancer, and repeated HIFU presented a survival benefit and did not increase risk.