No abstract

Granulomatous lobular mastitis (GLM) is a rare and chronic benign inflammatory disease of the breast. Difficulties exist in the management of GLM for many front-line surgeons and medical specialists who care for patients with inflammatory disorders of the breast. This consensus is summarized to establish evidence-based recommendations for the management of GLM. Literature was reviewed using PubMed from January 1, 1971 to July 31, 2020. Sixty-six international experienced multidisciplinary experts from 11 countries or regions were invited to review the evidence. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Experts discussed and concluded 30 recommendations on historical definitions, etiology and predisposing factors, diagnosis criteria, treatment, clinical stages, relapse and recurrence of GLM. GLM was recommended as a widely accepted definition. In addition, this consensus introduced a new clinical stages and management algorithm for GLM to provide individual treatment strategies. In conclusion, diagnosis of GLM depends on a combination of history, clinical manifestations, imaging examinations, laboratory examinations and pathology. The approach to treatment of GLM should be applied according to the different clinical stage of GLM. This evidence-based consensus would be valuable to assist front-line surgeons and medical specialists in the optimal management of GLM.

MSP is a safe and organ-preserving option for benign or low-grade malignant lesions in the neck and proximal body of the pancreas.

The high-mobility group box 1 (HMGB1) signaling pathway plays a crucial role in tumorigenesis and progression of many malignant cancers. The present study aimed to investigate the expression and clinical significance of HMGB1 in human primary liver cancer, and further explore the molecular mechanisms of HMGB1 in tumor growth and metastasis. Forty cases of human liver cancer and normal liver tissues were collected. The expression of HMGB1 was assessed using RT-PCR and western blot assays in biopsy samples. The HMGB1 pathway in vitro was blocked using transfection of the recombinant small hairpin RNA adenovirus vector rAd5-HMGB1 into the human liver cancer cell line SMMC-7721. The expression of HMGB1, phosphorylated AKT (p-AKT), Ki-67 and matrix metallopeptidase-2 (MMP-2) was detected by Real-PCR and western blot assays. Cell proliferative activities and metastatic capability were determined by MTT and Transwell assays. Cell cycle distribution and apoptosis were detected by flow cytometry. A subcutaneous xenograft tumor model was established, validating the effects of rAd5-HMGB1 on tumor growth in vivo. As a consequence, HMGB1 was found to be highly expressed in liver cancer compared with normal tissues, and was positively associated with pathological grade and distant metastases of liver cancer. Knockdown of HMGB1 downregulated the expression of p-AKT, Ki-67 and MMP-2, inhibited the proliferative activities and metastatic potential of SMMC-7721 cells, induced cell cycle arrest and apoptosis, and slowed the growth of xenograft tumors. Altogether, the expression of HMGB1 is closely correlated with pathological grade and distant metastases of liver cancer, and knockdown of HMGB1 inhibits liver cancer growth and metastasis, suggesting that HMGB1 may be involved in liver cancer development and progression through AKT-mediated regulation of Ki-67 and MMP-2 expression, and represent a potential therapeutic target for this aggressive malignancy.

Mesenchymal stem cell (MSC) therapy can prevent hepatic parenchymal cell loss and promote tissue repair. However, poor MSC engraftment is one of the primary barriers to the effectiveness of cell therapy because culture-expanded MSCs progressively downregulate C-X-C chemokine receptor type 4 (CXCR4) expression and lose their ability to migrate toward a concentration gradient of stromal cell-derived factor 1a (SDF1a). In this study, we investigated whether a CXCR4-MSC infusion could protect hepatocytes and stimulate regeneration in 50% reduced size liver transplantation (RSLT). Rats that underwent 50% RSLT were randomly divided into 3 groups: a phosphate-buffered solution group (PBS), a green fluorescent protein (GFP)-MSC group, and a CXCR4-MSC group. Rats received 1 mL of PBS with or without a resuspension of GFP-MSCs or CXCR4-MSCs. The factors secreted by MSCs, the graft function, the apoptosis and proliferation of hepatocytes, the efficacy of MSC engraftment, and the expression of SDF1a, albumin (Alb), and cytokeratin 18 (CK18) in engrafted GFP-positive MSCs were assessed. A systemic infusion of GFP-MSCs led to a reduction of the release of liver injury biomarkers and apoptosis of hepatocytes; CXCR4 overexpression did not further reduce the liver injury. However, CXCR4 overexpression enhanced MSC engraftment in liver grafts, improved the effect on the proliferation of hepatocytes, and thus provided a significant 1-week survival benefit. SDF1a expression in grafts was elevated after transplanted CXCR4-MSCs were recruited to the remnant liver. However, engrafted MSCs did not express the markers of hepatocytes, including Alb and CK18, in vivo 168 hours after transplantation. CXCR4 overexpression enhanced the mobilization and engraftment of MSCs into small-for-size liver grafts, in which these cells promoted the early regeneration of the remnant liver not by direct differentiation but perhaps by a paracrine mechanism.