Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre-metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr-1+ myeloid cells are characterized to form a pre-metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage-associated molecular patterns released from surgical resection contribute to the formation of pre-metastatic niche in lung through IL-1ß secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre-metastatic niche in lung which is with important implications for developing rational therapies during peri-operative period.

Patient-Derived Tumor Xenografts Plus Ex Vivo Models Enable Drug Validation for Tenosynovial Giant Cell Tumors.

INTRODUCTION: Tenosynovial giant cell tumor (TGCT) is a locally aggressive tumor with colony-stimulating factor 1 receptor (CSF1R) signal expression. However, there is a lack of better in vivo and ex vivo models for TGCT. This study aims to establish a favorable preclinical translational platform, which would enable the validation of efficient and personalized therapeutic candidates for TGCT. PATIENTS AND METHODS: Histological analyses were performed for the included patients. Fresh TGCT tumors were collected and sliced into 1.0-3.0 mm3 sections using a sterilized razor blade. The tumor grafts were surgically implanted into subrenal capsules of athymic mice to establish patient-derived tumor xenograft (PDTX) mouse models. Histological and response patterns to CSF1R inhibitors evaluations were analyzed. In addition, ex vivo cultures of patient-derived explants (PDEs) with endpoint analysis were used to validate TGCT graft response patterns to CSF1R inhibitors. RESULTS: The TGCT tumor grafts that were implanted into athymic mice subrenal capsules maintained their original morphological and histological features. The "take" rate of this model was 95% (19/20). Administration of CSF1R inhibitors (PLX3397, and a novel candidate, WXFL11420306) to TGCT-PDTX mice was shown to reduce tumor size while inducing intratumoral apoptosis. In addition, the CSF1R inhibitors suppressed circulating nonspecific monocyte levels and CD163-positive cells within tumors. These response patterns of engrafts to PDTX were validated by ex vivo PDE cultures. CONCLUSIONS: Subrenal capsule supports the growth of TGCT tumor grafts, maintaining their original morphology and histology. This TGCT-PDTX model plus ex vivo explant cultures is a potential preclinical translational platform for locally aggressive tumors, such as TGCT.

Total Arterial Off-Pump Coronary Artery Bypass Grafting: A 10-Year Experience / 中华医学杂志(英文版)

<p><b>Background</b>Arterial grafts had better mid-term and long-term patency than saphenous vein grafts in coronary artery bypass grafting (CABG). We summarized our experience with total arterial off-pump coronary artery bypass grafting (OPCAB) and assessed the early clinical results, surgical complications, and follow-up.</p><p><b>Methods</b>From January 2007 to May 2017, 508 coronary artery disease patients undergoing total arterial OPCAB were enrolled. Clinical features, approaches, outcomes of surgical treatments, and follow-up data of these patients were studied retrospectively. A total of 122 patients underwent single left internal mammary artery (IMA)-left anterior descending artery grafts, whereas the other 386 patients underwent multiple vessel grafts.</p><p><b>Results</b>The average distal anastomosis was 2.34 ± 0.97 (range: 1-4). All the patients were discharged from hospital except one died. A total of 457 (90.32%) patients were followed up. In the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was 1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate of repeat revascularization was 0.00%, 3.60%, and 8.67%; rate of ischemic symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%, and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the follow-up population.</p><p><b>Conclusions</b>Total arterial OPCAB with bilateral IMA, radial artery, and right gastroepiploic artery grafting yielded satisfactory early and midterm outcomes in this patient group, without a significant increase in early mortality or morbidity. Moreover, the long-term outcomes are also positive.</p>

Changes of interleukin-1beta and tumor necrosis factor-alpha of right atrial appendages in patients with rheumatic valvular disease complicated with chronic atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether atrial expression of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) of right atrial appendages are altered in patients with rheumatic valvular disease during chronic atrial fibrillation.</p><p><b>METHODS</b>A total of 48 patients with rheumatic heart disease were included. 27 patients had no history of atrial fibrillation, 21 patients had atrial fibrillation. Atrial tissue was obtained from the right atrial appendage during open heart surgery. The protein expression of IL-1beta and TNF-alpha was detected by immunohistochemistry method. The fibrosis of right atrial appendage was detected by Masson staining.</p><p><b>RESULTS</b>The fibrosis of right atrial appendage was significantly increased in patients with chronic atrial fibrillation. The protein expression of IL-1beta and TNF-alpha were significantly increased in patients with chronic atrial fibrillation.</p><p><b>CONCLUSIONS</b>The protein expression of IL-1beta and TNF-alpha were significantly increased in patients with rheumatic valvular disease during chronic atrial fibrillation. Inflammation may be one of the mechanisms for the development and persistence of atrial fibrillation.</p>