Extrinsic Adenomyosis Is Associated With Postoperative Recurrence of Ovarian Endometrioma

Objective: To determine whether endometrioma recurrence is closely related to the presence of extrinsic adenomyosis, which was demonstrated by magnetic resonance imaging (MRI).Design: Observational crosssectional study involving patients with the recurrence of ovarian endometrioma (OMA). Correlations of endometrioma recurrence and adenomyosis subtypes shown by MRI were analyzed.Method: Between January 2018 and December 2020, a total of 233 patients with recurrence of OMA after ovarian cystectomy were administered for surgery at our institution. All patients were divided into subtype II (Group A), subtype I+IV (Group B), and nonadenomyosis (Group C) groups at preoperative MRI imaging. The correlations of endometrioma recurrence with clinical features, imaging appearance, and surgical findings were retrospectively analyzed.Results: We found 112 (48.07%) patients of endometrioma recurrence combined with subtype II adenomyosis, 8 (3.43%) subtype I adenomyosis, 47 (20.17%) subtype IV adenomyosis, 66 (28.32%) nonadenomyosis. The mean time of OMA recurrence (44.28 ± 8.37, vs. 63.96 ± 10.28, vs. 69.36 ± 9.34 mon), rate of pain symptoms (85.71, vs. 69.10, vs. 18.18%), and primary infertility (31.25, vs. 14.55, vs. 10.77%) were higher in Group A. Uterine volume (257.37± 42.61, vs. 203.14 ± 33.52, vs. 100.85 ± 26.67 cm3), and mean OMA size (4.97 ± 2.25, vs. 4.36 ± 2.38, vs. 4.46 ± 2.70 cm) were significantly larger in Group A. The rate of DIE (83.93, vs. 45.45, vs. 40.91%), the number of DIE (3.6 ± 1.8 vs. 2.3 ± 1.5 vs. 2.2 ± 1.3), the mean total revised American Society for Reproductive Medicine score (rASRM, 103.14 ± 23.89 vs. 74.23 ± 16.72 vs. 36.51 ± 14.23) were significantly higher in Group A. After a multiple logistic regression analysis, extrinsic adenomyosis (OR 2.5, 95% CI 1.2–3.4), DIE lesions (OR 2.1, 95% CI 1.4–2.8), and primary infertility (OR 1.8, 95% CI 1.3–4.3) were significantly associated with early recurrence (in 3-year) of OMA.Conclusions: Extrinsic adenomyosis was associated with postoperative recurrence of OMA. In addition, a pathogenic link between extrinsic adenomyosis and pelvic endometriosis needs to be clarified.

Recurrence of Anti-semaphorin-3B Mediated Membranous Nephropathy after Kidney Transplantation

Background: Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early onset membranous nephropathy associated with Semaphorin 3B in 9 children and 2 adults. Methods: Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-Semaphorin antibodies were detected by Western blot and analyzed sequentially. Results: We report the first case of early recurrence after transplantation in a 7-year old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for Semaphorin 3B antigen. Western blot analysis of serum revealed antiSemaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histological MN recurrence with colocalization of Semaphorin 3B antigen and IgG (1). The patient was treated with rituximab. Anti-Semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab. Conclusion: This case provides evidence that anti-Semaphorin 3B antibodies are pathogenic and should be monitored in patients with membranous nephropathy.

The effect of the low stromal ratio induced by neoadjuvant chemotherapy on recurrence patterns in borderline resectable pancreatic ductal adenocarcinoma

The optimal regimens of neoadjuvant chemotherapy (NAC) and its biological and physiological modification of the tumor microenvironment (TME) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC) remain unknown. A deeper understanding of the complex stromal biology of the TME will identify new avenues to establish treatment strategies for PDAC patients. Herein, we sought to clarify whether stromal remodeling by NAC affects recurrence patterns and prognosis in BR PDAC patients. We retrospectively analyzed data from 104 BR PDAC patients who underwent pancreatectomy with or without NAC (upfront surgery [UpS], n = 44; gemcitabine + nab-paclitaxel [GnP], n = 28; and gemcitabine + S-1 [GS], n = 32) to assess the correlations of treatment with early recurrence, the stromal ratio, and Ki-67 levels. Eighty-six patients experienced recurrence, and those with liver metastasis had significantly shorter recurrence-free survival than those with other recurrence patterns. The frequency of liver metastasis was significantly higher in patients with a low stromal ratio than in those with a high stromal ratio in the NAC group but not in the UpS group. Patients in the GnP group had significantly higher Ki-67 than those in the GS and UpS groups. A low stromal ratio was positively correlated with high Ki-67 in the NAC group but not in the UpS group. The low stromal ratio induced by NAC promoted early liver metastasis in patients with BR PDAC. Our findings provide new insights into the complexity of stromal biology, leading to consideration of the optimal NAC regimen.

TPRG1 contributes to inflammation and cell proliferation of cystitis glandularis through regulating NF-кB/COX2/PGE2 axis

Cystitis glandularis is characterized by chronic inflammation and hyperproliferation of bladder mucosa, and contributes to progression of bladder adenocarcinoma. TPRG1 (Tumor Protein P63 Regulated 1) is related to cellular inflammatory response, and dysregulation of TPRG1 in tumor tissues is associated with tumor early recurrence. The effect of TPRG1 on cystitis glandularis was investigated in this study. Firstly, bladder specimen were isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Expression of TPRG1 was found to be up-regulated in the bladder specimen. Moreover, adeno-associated virus (AAV)-mediated silence of TPRG1 was delivered into rat, and data from hematoxylin and eosin (H & E) staining showed that injection with AAV-shTPRG1 ameliorated E. coli-induced histological changes in bladder tissues of rats, and suppressed the inflammatory response. Secondly, TPRG1 was also increased in primary cystitis glandularis cells. Knockdown of TPRG1 decreased cell proliferation of primary cystitis glandularis cells, and suppressed the migration. Thirdly, cyclooxygenase-2 (COX-2) was up-regulated in the bladder specimen isolated from patients with cystitis glandularis and E. coli-induced cystitis rat. Injection with AAV-shTPRG1 reduced protein expression of COX-2, p65 and prostaglandin E2 (PGE2) in the bladder specimen. Lastly, interference of COX-2 attenuated TPRG1 over-expression-induced increase of cell proliferation and migration in the primary cystitis glandularis cells. In conclusion, TPRG1 promoted inflammation and cell proliferation of cystitis glandularis through activation of NF-кB/COX2/PGE2 axis.

Surgical treatment of left-sided infective endocarditis in Hanoi Heart Hospital

Objective: to evaluate the short-term outcomes of surgical treatment of left-sided infective endocarditis (IE) in Hanoi Heart Hospital. Patients and Methods: A retrospective, cross-sectional and descriptive study on all patients underwent surgery for left-sided IE from 3/2015 to 3/2019 in Hanoi Heart Hospital. Result: 56 patients underwent surgery for left-sided IE in 4 years; the mean age was 45.8 ± 16.0; male-female ratio was 3.3/1. 9 patients (16.1%) had prosthetic valve endocarditis. Preopeative blood cultures were positive in 35.7%, the mainly microorganism was Streptococcus (21.4%). Emergency and urgent surgery was performed in 14.3%; the most frequently postoperative complication was kidney failure, the in-hospital mortality rate was 5.4%. During the average follow-up time of 36.6± 14.2 months, the recurrence rate of IE was 17.8%. Conclusion: surgical treatment of left-sided infective endocarditis is still a great challenge, the early recurrence and motality rate are high.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period

Background/purpose of the study Tumor heterogeneity based on copy number variations is associated with the evolution of cancer and its clinical grade. Clonal composition (CC) represents the number of clones based on the distribution of B-allele frequency (BAF) obtained from a genome-wide single nucleotide polymorphism (SNP) array. A higher CC number represents a high degree of heterogeneity. We hypothesized and evaluated that the CC number in hepatocellular carcinoma (HCC) tissues might be associated with the clinical outcomes of patients. Methods Somatic mutation, whole transcriptome, and CC number based on copy number variations of 36 frozen tissue samples of operably resected HCC tissues were analyzed by targeted deep sequencing, transcriptome analysis, and SNP array. Results The samples were classified into the heterogeneous tumors as poly-CC (n = 26) and the homogeneous tumors as mono-CC (n = 8). The patients with poly-CC had a higher rate of early recurrence and a significantly shorter recurrence-free survival period than the mono-CC patients (7.0 months vs. not reached, p = 0.0084). No differences in pathogenic non-synonymous mutations, such as TP53, were observed between the two groups when targeted deep sequencing was applied. A transcriptome analysis showed that cell cycle-related pathways were enriched in the poly-CC tumors, compared to the mono-CC tumors. Poly-CC HCC is highly proliferative and has a high risk of early recurrence. Conclusion CC is a possible candidate biomarker for predicting the risk of early postoperative recurrence and warrants further investigation.