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Radiation therapy (RT) recruits myeloid cells, leading to an immunosuppressive microenvironment that impedes its efficacy against tumors. Combination of immunotherapy with RT is a potential approach to reversing the immunosuppressive condition and enhancing tumor control after RT. This study aimed to assess the effects of local interleukin-12 (IL-12) therapy on improving the efficacy of RT in a murine prostate cancer model. Combined treatment effectively shrunk the radioresistant tumors by inducing a T helper-1 immune response and influx of CD8+ T cells. It also delayed the radiation-induced vascular damage accompanied by increased α-smooth muscle actin-positive pericyte coverage and blood perfusion. Moreover, RT significantly reduced the IL-12-induced levels of alanine aminotransferase in blood. However, it did not further improve the IL-12-induced anti-tumor effect on distant tumors. Upregulated expression of T-cell exhaustion-associated genes was found in tumors treated with IL-12 only and combined treatment, suggesting that T-cell exhaustion is potentially correlated with tumor relapse in combined treatment. In conclusion, this study illustrated that combination of radiation and local IL-12 therapy enhanced the host immune response and promoted vascular maturation and function. Furthermore, combination treatment was associated with less systemic toxicity than IL-12 alone, providing a potential option for tumor therapy in clinical settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors (PPIs) are commonly used for acid reduction in peptic ulcer diseases and esophageal reflux diseases. The effects of changing gut microbiota, and prolonged hypergastrinemia were reported. This study demonstrated that long-term PPI use in CRC patients was associated with an increased risk of death with dose–response effect but not for recurrence. PPIs may play a complex role in CRC patients. The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose–response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04–1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76–0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose–response effect in various dose level. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer. Considering the cost, potential adverse effects, including hypertension, proteinuria, bleeding, thromboembolic events, poor wound healing and gastrointestinal perforation, and no confirmed and accessible biomarkers for routine clinical use to direct patient selection for bevacizumab treatment, the identification of new predictive methods remains an urgent unmet medical need. This study identifies an effective biomarker and presents an automatic weakly supervised deep learning framework for patient selection and guiding ovarian cancer treatment. Ovarian cancer is a common malignant gynecological disease. Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer (EOC). Although careful patient selection is essential, there are currently no biomarkers available for routine therapeutic usage. To the authors' best knowledge, this is the first automated precision oncology framework to effectively identify and select EOC and peritoneal serous papillary carcinoma (PSPC) patients with positive therapeutic effect. From March 2013 to January 2021, we have a database, containing four kinds of immunohistochemical tissue samples, including AIM2, c3, C5 and NLRP3, from patients diagnosed with EOC and PSPC and treated with bevacizumab in a hospital-based retrospective study. We developed a hybrid deep learning framework and weakly supervised deep learning models for each potential biomarker, and the experimental results show that the proposed model in combination with AIM2 achieves high accuracy 0.92, recall 0.97, F-measure 0.93 and AUC 0.97 for the first experiment (66% training and 34%testing) and high accuracy 0.86 ± 0.07, precision 0.9 ± 0.07, recall 0.85 ± 0.06, F-measure 0.87 ± 0.06 and AUC 0.91 ± 0.05 for the second experiment using five-fold cross validation, respectively. Both Kaplan-Meier PFS analysis and Cox proportional hazards model analysis further confirmed that the proposed AIM2-DL model is able to distinguish patients gaining positive therapeutic effects with low cancer recurrence from patients with disease progression after treatment (p < 0.005). [ABSTRACT FROM AUTHOR]

Evidence regarding the effect of a face-down posture (FDP) for large idiopathic macular hole (IMH) is inconsistent. We conducted a systematic review and meta-analysis to determine whether a postoperative FDP is required for the treatment of large IMH. Eligible randomized controlled trials published before September 2021 were retrieved from the Medline, Embase, and Cochrane Library databases. The efficacy outcome was the IMH closure rate and the visual acuity improvement rate. A meta-analysis was performed using a random effects model. The "Grading of Recommendations Assessment, Development, and Evaluation" approach was implemented, and the numbers needed-to-treat (NNTs) were calculated. Seven studies comprising 640 patients were included. We performed a predefined subgroup analysis of IMH size using a cut-off point of 400 µm. Compared with non-FDP, a significant effect of FDP was found in the IMH > 400 µm group (OR = 3.34; 95% CI = 1.57–7.14; trial sequential analysis-adjusted CI = 1.20–11.58; NNTs = 7.9). After stratifying by the posturing periods, the beneficial effect of FDP lasting at least five days, but not three days was observed for large IMH. Maintaining a FDP for at least five days postoperatively is an effective strategy (certainty of evidence: "moderate") for treating large IMH. [ABSTRACT FROM AUTHOR]

This study investigated the clinical outcome of locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who received curative concurrent chemoradiotherapy (CCRT) and their differences from thoracic ESCC patients. Among 411 enrolled ESCC patients, including 63 with cervical and 348 with thoracic ESCC, 63 thoracic patients were propensity score-matched to the 63 cervical patients. For cervical ESCC, T4b and high tumor grade were independent prognostic factors of a worse overall survival (OS) in univariate and multivariate analyses. The response rates to curative CCRT between cervical and the matched thoracic ESCC groups were similar but cervical ESCC had a better OS than that of the matched thoracic group (21.4 versus 10.1 months, p = 0.012). Better OS was mentioned to be in the patients with complete response (CR), whether in the cervical or matched thoracic ESCC group. For patients without CR, patients who underwent esophagectomy had superior OS than those without operation in the matched thoracic ESCC group (11.6 versus 11.9 months, p = 0.73). Only three patients received operation in the cervical ESCC group, thus the survival difference was not significant. Curative CCRT may be a reasonable treatment for cervical ESCC in clinical practice, and the role of surgery should be considered as salvage therapy if residual disease is evident. [ABSTRACT FROM AUTHOR]