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Background: The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA).Methods: This is a prospective, observational study on GCLM patients with 1-3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS).Results: Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group.Conclusion: The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA. [ABSTRACT FROM AUTHOR]

Background: The main aim of this study was to investigate comprehensively the clinical effect of hepatic arterial infusion chemotherapy (HAIC) on patients suffering from hepatocellular carcinoma (HCC). Methods: The following electronic databases were searched for eligible articles published from inception to July 2020: PubMed, Web of Science, Embase, and Cochrane Library. The main final indicators were overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). Results: A total of 26 studies entailing 4,506 cases were included for a meta-analysis. The results showed that HAIC could improve advanced HCC patients' OS (HR, 0.49; 95% CI: 0.37–0.61) and PFS (HR, 0.52; 95% CI: 0.36–0.68). Remarkably, compared with Japan (HR, 0.58) and Korea (HR, 0.54), for the unresectable HCC patients, the HAIC group achieved higher efficacy on OS than the control group in China (HR, 0.24). The resectable HCC patients, who received HAIC adjuvant chemotherapy, exhibited favorable prognosis for OS (HR, 0.58; 95% CI: 0.27–0.88) and DFS (HR, 0.49; 95% CI: 0.31–0.68). Conclusion: HAIC improved long-term survival for both resectable and unresectable HCC patients in comparison with other therapies. However, the clinical effect of HAIC needs to be ascertained by large-scale well-designed studies. [ABSTRACT FROM AUTHOR]

Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Besides, a stronger association between gene mutations and TIME was observed in RCC. Specifically, using multi-omics data, we demonstrated the mutations of most top mutated genes (TMGs) including BRAF, PCLO, MUC16, LRP2, ANK3, KMT2D, RYR2 made great contributions to elevated fraction of immune cells by up-regulating immune-related genes directly or indirectly through miRNA and DNA methylation, whereas the effects of APC, TP53 and KRAS mutations on TIME were reversed in RCC. Remarkably, we found the expression levels of several immune checkpoint molecules such as PD-1 and LAG3 were correlated with corresponding DNA methylation levels, which were associated with the mutations of TMGs in RCC. In contrast, the associations between gene mutations and TIME were less significant in LCC. Besides, survival analyses showed APC mutation had adverse impact on immunotherapy while patients with BRAF mutation were more suitable for immunotherapy in colon cancer. We hope that our results will provide a deeper insight into the sophisticated mechanism underlying the regulation between mutations and TIME, and thus boost the discovery of differential immunotherapeutic strategies for RCC and LCC. [ABSTRACT FROM AUTHOR]

Treatment of urolithiasis depends on several important factors which include stone location, size, composition, and patient symptoms. Although significant advancements have been made in the surgical management of urolithiasis in the last decade, pharmacotherapy which can prevent the formation of new stones and decrease the recurrence of urolithiasis has not experienced the same level of success. Currently, urolithiasis is regarded as a complicated syndrome that is determined by numerous factors, and any treatment plan for urolithiasis should be individualized while considering any potential damage arising from stone-forming factors. This review introduces the most popular methods currently used to evaluate urolithiasis and the pharmacotherapy of urolithiasis based on patient-specific factors. [ABSTRACT FROM AUTHOR]

Background and Aim: Studies had shown that tenofovir (TDF) and entecavir (ETV) are widely used as the first‐line therapy to inhibit hepatitis B virus replication, which can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it was unclear which nucleos(t)ide analogue was most effective. Therefore, we performed a meta‐analysis and a systematic review to compare the incidence of HCC in CHB patients who are either on TDF or ETV. Methods: For this study, the following databases were searched for clinical trials published from its inception until November 2019: PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library. Results: A total of 11 eligible studies were selected, including 70 864 patients. The meta‐analysis showed that TDF was superior to ETV with regard to the incidence of HCC, the incidence of death or transplantation, and virologic response. There were no significant differences in terms of biochemical response and loss of seroconversion response among the entire cohort. Conclusions: The conclusion was that CHB patients treated with TDF had a reduced incidence of HCC compared with patients treated with ETV. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. Methods: The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events. Results: The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34–0.53, p < 0.001; HR, 0.79, 95% CI 0.65–0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system. Conclusions: PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs. [ABSTRACT FROM AUTHOR]

The present study investigated the use of retrograde flexible ureteroscopy (RFU) in the discrimination of the etiology of hematuria that originates from the upper urinary tract (UUT). The present study collected retrospective data for patients who presented with hematuria and cystoscopy-detected bleeding from the UUT between June 2006 and August 2018 in Ningbo First Hospital. All patients accepted RFU to determine the etiology of hematuria. Data regarding imaging examinations, surgery, pathology and complications were also collected and analyzed. In total, 65 patients (males, 38; females, 27) with a mean age of 63 years underwent RFU to determine the etiology of hematuria originating from the UUT. Using RFU, UUT tumors were found in 29 cases. Stones, polyps and atypical hyperplasia were found in two cases, and a definite diagnosis was not found in three cases. There were 17 cases without obvious abnormalities and nine cases were unable to undergo RFU due to ureteral stenosis. In patients who could not be diagnosed by imaging examination, 34.4% (11/32) were diagnosed with urothelial carcinoma by RFU, and these results were also confirmed by postoperative pathology. In the present study, no patient had severe complications after RFU. The present results suggested RFU may be used as a sensitive method to diagnose UUT tumors (78.4%; 29/37) and has strong specificity. RFU could be performed as a routine examination for patients with hematuria from the UUT. [ABSTRACT FROM AUTHOR]

Motivation Genome-scale CRISPR/Cas9 system has been a democratized gene editing technique and widely used to investigate gene functions in some biological processes and diseases especially cancers. Aiming to characterize gene aberrations and assess their effects on cancer, we designed a pipeline to identify the essential genes for pan-cancer. Methods CRISPR screening data were used to identify the essential genes that were collected from published data and integrated by Robust Rank Aggregation algorithm. Then, hypergeometrics test and random walks with restart (RWR) were used to predict additional essential genes on broader scale. Finally, the expression status and potential roles of these genes were explored based on TCGA portal and regulatory network analysis. Results We collected 926 samples from 10 CRISPR-based screening studies involving 33 different types of cancer to identify cancer-essential genes, which consists of 799 protein-coding genes (PCGs) and 97 long non-coding RNAs (lncRNAs). Then, we constructed a 'bi-colored' network with both PCGs and lncRNAs and applied it to predict additional essential genes including 495 PCGs and 280 lncRNAs on a broader scale using hypergeometrics test and RWR. After obtaining all essential genes, we further investigated their potential roles in cancer and found that essential genes have higher and more stable expression levels, and are associated with multiple cancer-associated biological processes and survival time. The regulatory network analysis detected two intriguing modules of essential genes participating in the regulation of cell cycle and ribosome biogenesis in cancer. Availability and implementation   Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Cervical cancer is a global health challenge in women. Neoadjuvant chemotherapy (NACT) is a recent prospect for alternative cervical cancer treatments. This study investigated the efficacy of NACT against resectable cervical cancer based on the medium and long-term survival of patients with the disease. We searched through PubMed, Web of Science, EBSCO and Cochrane Library for relevant reports published by June 2020. The primary outcomes were 3-year and 5-year progression-free survival (PFS) and overall survival (OS) of patients with resectable cervical cancer. Overall, 22 publications encompassing 5627 patients fulfilled the inclusion criteria. We found NACT not to affect both 3-year PFS and OS as well as 5-year PFS of patients with resectable cervical cancer. However, NACT significantly improves the 5-year OS of patients with resectable cervical cancer (HR = 0.83, 95% CI: 0.73-0.94, p = 0.013). Subgroup analysis (RCTs, non-RCTs, NACT + surgery + AT vs. surgery + AT, NACT + surgery + AT vs. CCRT/RT/CRT) further revealed NACT had no significant effect on 5-year PFS of patients with resectable cervical cancer, converse to the 5-year OS subgroup analysis, which validated the beneficial effect of NACT in patients with resectable cervical cancer. In addition, the effect of NACT was most significant in the non-RCTs subgroup (p = 0.012). NACT may improve the long-term prognosis of patients with resectable cervical cancer. However, further large-scale multicenter studies are needed to validate this finding., Competing Interests: Declaration of competing interest The authors declare there was no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Lung cancer has been the focus of attention for many researchers in recent years for the leading contribution to cancer-related death worldwide, in which lung adenocarcinoma (LUAD) is the most common histological type. However, the potential mechanism behind LUAD initiation and progression remains unclear. Aiming to dissect the tumor microenvironment of LUAD and to discover more informative prognosis signatures, we investigated the immune-related differences in three types of genetic or epigenetic characteristics (expression status, somatic mutation, and DNA methylation) and considered the potential roles that these alterations have in the immune response and both the immune-related metabolic and neural systems by analyzing the multi-omics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct the prognostic prediction model. For the prognostic predictions on the independent test set, the performance of the trained models (average concordance index [C-index] = 0.839) is satisfied, with average 1-year, 3-year, and 5-year areas under the curve (AUCs) equal to 0.796, 0.786, and 0.777. Finally, the overall model was constructed based on all samples, which comprised 27 variables and achieved a high degree of accuracy on the 1-year (AUC = 0.861), 3-year (AUC = 0.850), and 5-year (AUC = 0.916) survival predictions., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)