Molecular and Cellular Insights into the Development of Uterine Fibroids.

Uterine leiomyomas represent the most common benign gynecologic tumor. These hormone-dependent smooth-muscle formations occur with an estimated prevalence of ~70% among women of reproductive age and cause symptoms including pain, abnormal uterine bleeding, infertility, and recurrent abortion. Despite the prevalence and public health impact of uterine leiomyomas, available treatments remain limited. Among the potential causes of leiomyomas, early hormonal exposure during periods of development may result in developmental reprogramming via epigenetic changes that persist in adulthood, leading to disease onset or progression. Recent developments in unbiased high-throughput sequencing technology enable powerful approaches to detect driver mutations, yielding new insights into the genomic instability of leiomyomas. Current data also suggest that each leiomyoma originates from the clonal expansion of a single transformed somatic stem cell of the myometrium. In this review, we propose an integrated cellular and molecular view of the origins of leiomyomas, as well as paradigm-shifting studies that will lead to better understanding and the future development of non-surgical treatments for these highly frequent tumors.

Intensive Debulking Chemotherapy Improves the Short-Term and Long-Term Efficacy of Anti-CD19-CAR-T in Refractory/Relapsed DLBCL With High Tumor Bulk.

Anti-CD19 chimeric antigen receptor T (CAR-T) therapy has achieved remarkable effects in refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL). However, when high tumor bulk occurs, patients tend to early progression after CAR-T therapy. Here, we investigated whether pretreatment with intensive debulking chemotherapy could improve the outcome of CAR-T in such patients. Fifty-seven patients with R/R DLBCL were enrolled, and 42 patients received anti-CD19-CAR-T therapy, among which, 25 patients (the combined group) with high tumor bulk received debulking chemotherapy and anti-CD19-CAR-T therapy sequentially. Another 17 patients (the control group) without high tumor bulk received anti-CD19-CAR-T therapy only. According to the response to debulking chemotherapy, patients of the combined group were divided into chemo-sensitive and chemo-refractory groups. Within 2 months, the objective response rate (ORR) was higher in the chemo-sensitive group than in the chemo-refractory group (P = 0.031). Grades 1-3 cytokine release syndrome (CRS) was reported, and no difference was shown in CRS grade distribution between the chemo-sensitive and chemo-refractory groups (P = 0.514). The chemo-sensitive group demonstrated longer overall survival (OS) than the chemo-refractory group (P = 0.042). Of the chemo-sensitive group, the 1-year disease free survival (DFS) and OS rates were 52.6 and 57.9%, respectively. Besides, no significant differences were found in ORR, DFS, and OS between the chemo-sensitive and control groups (ORR: P = 0.593; DFS: P = 0.762; OS: P = 0.531). In summary, effective debulking chemotherapy improved the short-term ORR and long-term OS of CAR-T therapy in R/R DLBCL with high tumor bulk, with outcomes comparable to those of R/R DLBCL without high tumor bulk. The clinical trial of our study was registered at http://www.chictr.org.cn/index.aspx as ChiCTR-ONN-16009862 and ChiCTR1800019622. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx, identifier (ChiCTR-ONN-16009862 and ChiCTR1800019622).

High Diagnostic Accuracy of Visible 5-ALA Fluorescence in Meningioma Surgery According to Histopathological Analysis of Tumor Bulk and Peritumoral Tissue.

BACKGROUND AND OBJECTIVES: Complete neurosurgical resection of intracranial meningiomas is essential to avoid residual tumor tissue and thus minimize the risk of tumor recurrence. However, local recurrence of meningiomas is not uncommon mainly due to insufficient intraoperative detection of residual tumor tissue within the tumor bulk or peritumoral tissue such as bone and satellite lesions. Although 5-aminolevulinic acid (5-ALA) induced fluorescence was found to visualize the majority of meningiomas, no comprehensive histopathological assessment of fluorescing samples from the tumor bulk and peritumoral tissue is available. The aim of our study was thus to histopathologically analyze a large series of tissue samples derived from meningioma surgery to assess the positive predictive value (PPV) of visible 5-ALA fluorescence. STUDY DESIGN/MATERIALS AND METHODS: In this study, we retrospectively investigated a series of tissue samples with visible 5-ALA fluorescence collected during surgery of intracranial meningiomas from the tumor bulk and peritumoral tissue including the bone flap, dura/dural tail, arachnoidea, adjacent cortex, and satellite lesions. The tumor diagnosis was established according to the World Health Organization (WHO) criteria and all collected fluorescing samples were screened for presence of tumor tissue to calculate the PPV. RESULTS: Altogether, 191 tissue samples with visible 5-ALA fluorescence derived during surgery of 85 meningiomas (63 WHO grade I, 17 WHO grade II, and 5 WHO grade III) were included. In detail, 158 samples from the tumor bulk and 33 specimens from the peritumoral tissue were investigated. According to histopathological analysis, the PPV of 5-ALA fluorescence was significantly higher in samples from the tumor bulk (100%) as compared with peritumoral tissue (73%; P < 0.001). With regard to peritumoral tissue, tumor tissue was present in most fluorescing samples from the satellite lesions (100%), the bone flap (92%), arachnoidea (83%), and dura/dural tail (75%). In contrast, tumor tissue was absent in the majority of samples from fluorescing cortex (six of seven samples; 86%). However, distinct reactive tissue alterations were found in all six tumor-free fluorescing cortex samples and additional vascular proliferation in two cases. CONCLUSION: In this largest series to date, visible 5-ALA fluorescence is characterized by a high PPV detecting tumor bulk and peritumoral tissue in intracranial meningiomas. Thus, 5-ALA fluorescence supports the neurosurgeon in identifying residual tumor tissue at relevant surgical sites to optimize meningioma surgery and minimize the risk of local recurrence. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Correlation of post-contrast T1-weighted MRI surface regularity, tumor bulk, and necrotic volume with Ki67 and p53 in glioblastomas.

PURPOSE: p53 and Ki67 status can be relevant to the management of glioblastoma. The goal of this study is to determine whether tumor morphology and bulk depicted on MRI correlate with p53 and Ki67 in glioblastoma. METHODS: A retrospective review of 223 patients with glioblastoma and corresponding p53 or Ki67 status, along with T1-weighted post-contrast MR images was performed. Enhancing tumors were outlined for determining surface regularity, tumor bulk, and necrotic volume. The median value of 0.1 was chosen for p53 and 0.2 for Ki67 to separate each data set into two classes. T tests and receiver operating characteristic analysis were performed to determine the separation of the classes and the predicting power of each feature. RESULTS: There were significant differences between tumor surface regularity (p = 0.01) and necrotic volume (p = 0.0429) according to Ki67 levels, although neither had statistically significant predictive power (AUC = 0.697, p = 0.0506 and AUC = 0.577, p = 0.164, respectively). There were also significant differences between tumor bulk (p = 0.0239) and necrotic volume (p = 0.0200) according to p53 levels, but again no significant predictive power was found using ROC analysis (AUC = 0.5882, p = 0.0894 and AUC = 0.567, p = 0.155, respectively). CONCLUSION: Quantitative morphological tumor characteristics on post-contrast T1-weighted MRI can to a certain degree provide insights regarding Ki67 and p53 status in patients with glioblastoma.

Retinoblastoma: Result of Radiotherapy / 대한치료방사선과학회지

Radiotherapy result was analyzed in 23 children with retinoblastoma treated in Seoul National University Hospital from 1980 to 1987. Three (17%) had bilateral tumor at diagnosis. Among 20 children with unilateral retinoblastoma 13 children got radiotherapy after enucleation, 2 were treated with radiotherapy alone, and 5 were delivered with radiotherapy after relapse. Of 15 non-recurrent unilateral tumors, there were 5 stage II children, 8 stage III, and 2 stage IV by staging system proposed by St. Jude Children's Research Hospital. Chemotherapy was combined when resection margin of the optic nerve was positive or when malignant cell was found in SCF. Of 12 children who completed radiotherapy, local or distant failure was not found but 2 cases of relapse at the contralateral retina were observed. Their 5 year survival rate was 82.2%. Another case of contralateral relapse was detected in children who was treated with radiotherapy alone. Thus overall frequency of the bilateral disease was 33%. Prognosis of recurrent tumors were so poor that no cases of CR was obtained and that 3 year survival rate was 20%. Two of 3 bilateral cases at diagnosis were in NED status. Complication were sunken orbit only. Result of radiotherapy was so good in early stage or small bulk tumor that treatment delay after diagnosis must not be allowed.

Combined Surgery and Radiotherapy in the Stage I and II Primary Gastrointestinal Non-Hodgkin's Lymphomas / 대한치료방사선과학회지

Thirty eight patients with stage Iand II primary gastrointestinal non-Hodgkin's lymphoma were treated in the Department of Therapeutic Radiology, Seoul National University Hospital between 1979 and 1984. There were 6 systemic disseminations during radiotherapy, and the overall failure rate were 31% in the cases with tumor bulk less than 5 cm in diameter before radiotherapy and 75% in the cases with tumor bulk greater than 5 cm in diameter (p<0.05). The overall 5 year survival rate were 69.2% in 28 patients who completed radiotherapay and 72% in 24 patients with tumor bulk less than 5 cm in diameter (small or no tumor bulk). The 5 year disease free survival rate were 71% in cases with tumor bulk less than 5 cm in diameter and 25% in cases with tumor bulk greater than 5 cm in diameter (p<0.01). But the initial stage was not related with treatment result in all cases or subgroups of cases. Thus the cases with small or no tumor bulk were shown to be curable with combined surgery and postoperative radiotherapy, but for the control of the cases with large tumor bulk that had a guarded prognosis combined radiotherapy and chemotherapy should be tried.