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Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (−)] GC. The tumor cell-intrinsic cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS–STING was highly expressed in dMMR GC compared to pMMR/EBV (−) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8+ tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (−). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment. [ABSTRACT FROM AUTHOR]

Cardiac tamponade is a rare postoperative complication of esophagectomy, with no previous reports of association with coronary artery aneurysm rupture. We present a case of cardiac tamponade caused by coronary aneurysm rupture following esophageal cancer surgery. A 68-year-old man with no history of heart disease underwent robotic subtotal esophagectomy for esophageal squamous cell carcinoma. He experienced intermittent chest pain on postoperative day (POD) 17. Echocardiography revealed increasing pericardial fluid, and pericardiocentesis on POD 34 revealed bloody pericardial fluid. Contrast-enhanced computed tomography and coronary angiography revealed a ruptured coronary aneurysm causing cardiac tamponade. Emergency surgery with a median sternotomy achieved hemostasis, and the patient recovered successfully. Cardiac tamponade after esophageal surgery, particularly from coronary aneurysm rupture, is rare. Prompt diagnosis and treatment are crucial for patient survival. Despite its risks, median sternotomy was effective in achieving rapid hemostasis and patient recovery in this case. [ABSTRACT FROM AUTHOR]

Local differential privacy algorithms combined with deep generative models can enhance secure medical image sharing among researchers in the public domain without central administrators; however, these images were limited to the generation of low-resolution images, which are very insufficient for diagnosis by medical doctors. To enhance the performance of deep generative models so that they can generate high-resolution medical images, we propose a large-scale diffusion model that can, for the first time, unconditionally generate high-resolution ( 256 × 256 × 256 ) volumetric medical images (head magnetic resonance images). This diffusion model has 19 billion parameters, but to make it easy to train it, we temporally divided the model into 200 submodels, each of which has 95 million parameters. Moreover, on the basis of this new diffusion model, we propose another formulation of image anonymization with which the processed images can satisfy provable Gaussian local differential privacy and with which we can generate images semantically different from the original image but belonging to the same class. We believe that the formulation of this new diffusion model and the implementation of local differential privacy algorithms combined with the diffusion models can contribute to the secure sharing of practical images upstream of data processing. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy has the potential to induce CD8+ T-cell infiltration in the tumor microenvironment (TME) and activate the anti-tumor immune response in several cancers including esophageal squamous cell carcinoma (ESCC). The tumor cell-intrinsic cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has been known as a critical component for regulating immune cell activation in the TME. However, its effect on the infiltration of immune cells induced by chemotherapy in the ESCC TME has not been investigated. Methods: We examined the effect of the tumor-cell intrinsic cGAS–STING pathway on the infiltration of CD8+ T cells induced by chemotherapy in ESCC using ESCC cell lines and surgically resected ESCC specimens from patients who received neoadjuvant chemotherapy (NAC). Results: We found that chemotherapeutic agents, including 5-fluorouracil (5-FU) and cisplatin (CDDP), activated the cGAS–STING pathway, consequently inducing the expression of type I interferon and T-cell-attracting chemokines in ESCC cells. Moreover, the tumor cell-intrinsic expression of cGAS–STING was significantly and positively associated with the density of CD8+ T cells in ESCC after NAC. However, the tumor cell-intrinsic expression of cGAS–STING did not significantly impact clinical outcomes in patients with ESCC after NAC. Conclusion: Our findings suggest that the tumor cell-intrinsic cGAS–STING pathway might contribute to chemotherapy-induced immune cell activation in the ESCC TME. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to develop a biomarker predicting the efficacy of chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT) for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with each therapy. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ central memory T cells (TCM) were significantly decreased during NT in the progressive disease group. Taken together, the alteration in frequency of TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients. In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ CD45RA−CD27+CD127+ central memory T cells (TCM) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA−CD27+CD127+ TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment in colorectal cancer (CRC), its impact on the infiltration of immune cells and clinical outcomes in patients with mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC has not been thoroughly investigated. In this study, we examine the expression pattern of cGAS-STING in tumor cells and its effect on the infiltrations of CD8+ and CD4+ T cells, as well as clinical outcomes including survival and recurrence in patients with pMMR/MSS CRC. Our current findings may offer novel insights and therapeutic strategies for patients with pMMR/MSS CRC. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8+ T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS−/STING−) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS+/STING+) in tumor cells. The frequency of cGAS+/STING+ cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8+ and/or CD4+ T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate whether it is useful for junior physicians to use a three‐dimensional (3D) kidney model when evaluating the R.E.N.A.L. nephrometry score. Materials and Methods: An expert and four urology residents retrospectively evaluated the R.E.N.A.L. nephrometry scores of 64 renal tumors (62 patients) that underwent robot‐assisted partial nephrectomy at our hospital. The expert evaluated 64 R.E.N.A.L. nephrometry scores with computed tomography (CT), whereas four residents evaluated 32 cases using CT alone and the other 32 cases using CT and a 3D kidney model. The consistency between the expert and residents was assessed by Cohen's kappa score. Patient‐specific 3D kidney models were created in a gird style using a 3D printer based on CT or magnetic resonance imaging of the patient. Results: For all four residents, the accuracy of the overall R.E.N.A.L. nephrometry score was significantly higher with the 3D model and CT than with CT alone (P <.001). Regarding the individual components of the R.E.N.A.L. nephrometry score, the accuracy rates of "E," "N," "A," and "L" scores were higher with the 3D model and CT than with the CT alone (P =.020–.089). Conclusion: Patient‐specific 3D‐printed kidney models could improve the resident's understanding of the renal tumor complexity and could be an important educational tool for residents. [ABSTRACT FROM AUTHOR]