ABSTRACT
BACKGROUND: The standard treatment for gestational choriocarcinoma is chemotherapy. OBJECTIVE: To describe the risk of recurrence with expectant management of gestational choriocarcinoma that has reached a normal human chorionic gonadotropin level after tumor removal without adjuvant chemotherapy. METHODS: A retrospective multicenter international cohort study was conducted from 1981 to 2017 involving 11 gestational trophoblastic disease reference centers with patient's follow-up extended until 2023. Clinical and biological data of included patients were extracted from each center's database. The inclusion criteria were i) histological diagnosis of gestational choriocarcinoma in any kind of placental tissue retrieved, ii) spontaneous normalization of human chorionic gonadotropin level following choriocarcinoma retrieval, iii) patient did not receive any oncological treatment for the choriocarcinoma, iv) and at least 6 months of follow-up after the first human chorionic gonadotropin level normalization. RESULTS: Among 80 patients with retrieved gestational choriocarcinoma and whose human chorionic gonadotropin level normalized without any other oncological therapy, none had a recurrence of choriocarcinoma after a median follow-up of 50 months. The median interval between choriocarcinoma excision and human chorionic gonadotropin level normalization was 48 days. The International Federation of Gynecology and Obstetrics/World Health Organization risk score was ≤6 in 93.7% of the cases. CONCLUSIONS: This multicenter international study reports that selected patients with gestational choriocarcinoma managed in gestational trophoblastic disease reference centers did not experience any relapse when the initial tumor evacuation is followed by human chorionic gonadotropin level normalization without any additional treatment. Expectant management may be a safe approach for highly selected patients.
Subject(s)
Choriocarcinoma , Gestational Trophoblastic Disease , Uterine Neoplasms , Humans , Pregnancy , Female , Cohort Studies , Chorionic Gonadotropin/therapeutic use , Neoplasm Recurrence, Local , Placenta/pathology , Gestational Trophoblastic Disease/drug therapy , Gestational Trophoblastic Disease/surgery , Gestational Trophoblastic Disease/pathology , Choriocarcinoma/drug therapy , Uterine Neoplasms/drug therapy , Uterine Neoplasms/surgeryABSTRACT
OBJECTIVES: To assess the use of molecular genotyping to accurately diagnose and treat human chorionic gonadotropin (hCG)-producing tumors and to evaluate the discriminating capacity of molecular testing on prognosis and overall survival. METHODS: We conducted a retrospective descriptive study of patients registered with the French Reference Center for Trophoblastic Disease between 1999 and 2021. We included all patients with hCG-producing tumors for whom results of molecular genotyping were available. RESULTS: Fifty-five patients with molecular genotyping were included: 81.2 % (n = 45) had tumors of gestational origin, 12.7 % (n = 7) of non-gestational origin and 5.5 % (n = 3) of undetermined origin. The results of molecular genotyping influenced the treatment decisions for 17 % of patients in this cohort. Overall survival was 93.3 % for patients with gestational tumors (after a median follow-up of 74 months) compared to 71.4 % for patients with non-gestational tumors (after a median follow-up of 23 months). CONCLUSION: In atypical presentations of hCG-producing tumors, molecular genotyping is a valuable tool to guide diagnosis and tailor treatment recommendations.
Subject(s)
Gestational Trophoblastic Disease , Uterine Neoplasms , Pregnancy , Female , Humans , Uterine Neoplasms/diagnosis , Retrospective Studies , Genotype , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/genetics , Gestational Trophoblastic Disease/therapy , Chorionic GonadotropinABSTRACT
BACKGROUND: BRAF inhibitors are approved in BRAFV600-mutated metastatic melanoma, non-small-cell lung cancer (NSCLC), Erdheim-Chester disease (ECD), and thyroid cancer. We report here the efficacy, safety, and long-term results of single-agent vemurafenib given in the AcSé vemurafenib basket study to patients with various BRAF-mutated advanced tumours other than BRAFV600-mutated melanoma and NSCLC. PATIENTS AND METHODS: Patients with advanced tumours other than BRAFV600E melanoma and progressing after standard treatment were eligible for inclusion in nine cohorts (including a miscellaneous cohort) and received oral vemurafenib 960 mg two times daily. The primary endpoint was the objective response rate (ORR) estimated with a Bayesian design. The secondary outcomes were disease control rate, duration of response, progression-free survival (PFS), overall survival (OS), and vemurafenib safety. RESULTS: A total of 98 advanced patients with various solid or haematological cancers, 88 with BRAFV600 mutations and 10 with BRAFnonV600 mutations, were included. The median follow-up duration was 47.7 months. The Bayesian estimate of ORR was 89.7% in hairy cell leukaemias (HCLs), 33.3% in the glioblastomas cohort, 18.2% in cholangiocarcinomas, 80.0% in ECD, 50.0% in ovarian cancers, 50.0% in xanthoastrocytomas, 66.7% in gangliogliomas, and 60.0% in sarcomas. The median PFS of the whole series was 8.8 months. The 12-, 24-, and 36-month PFS rates were 42.2%, 23.8%, and 17.9%, respectively. Overall, 54 patients died with a median OS of 25.9 months, with a projected 4-year OS of 40%. Adverse events were similar to those previously reported with vemurafenib. CONCLUSION: Responses and prolonged PFS were observed in many tumours with BRAF mutations, including HCL, ECD, ovarian carcinoma, gliomas, ganglioglioma, and sarcomas. Although not all cancer types responded, vemurafenib is an agnostic oncogene therapy of cancers.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Melanoma , Sarcoma , Humans , Vemurafenib/pharmacology , Vemurafenib/therapeutic use , Melanoma/drug therapy , Melanoma/genetics , Proto-Oncogene Proteins B-raf/genetics , Bayes Theorem , Treatment Outcome , Sulfonamides/adverse effects , Disease-Free Survival , MutationABSTRACT
Objective: To compare the efficacy of off-pump minimally invasive cardiac surgery (MICS) via a single left intercostal space incision with median sternotomy multi-vesselcoronary artery bypass grafting (CABG). Methods: Patients who were diagnosed with multi-artery coronary artery disease (CAD) in the Ward 10 of the Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University and underwent CABG from July 2019 to January 2022 were retrospectively collected. All the patients were divided into MICS group and conventional CABG group according to the surgical methods. The perioperative outcomes were compared between thetwo groups, including intraoperative blood loss, postoperative 24 h thoracic drainage volume, ventilation duration, length of stay (LOS) in intensive care unit (ICU) and total LOS in hospital. Intraoperative blood flow of graft vesselswas measured by transit-time flow measurement (TTFM) after vascular anastomosis, and mean flow (MF) and pulsatile index (PI) were compared between the two groups. Results: A total of 444 patients were in the final analysis, with 351 males and 93 females, and the mean age of (62.0±8.9) years. There were 179 patients in MICS group and 265 cases in conventional CABG group, respectively. There were no statistically significant differences in the preoperative profiles between the two groups (all P>0.05) except that younger age [(60.7±9.3) years vs (62.8±8.5) years, P=0.017] and lower proportion of female [10.1% (18/179) vs 28.3% (75/265), P<0.001] were detected in MICS group. Likewise, there was no significant difference in the number of graft vessels between MICS group (3.18±0.74) and conventional CABG group (3.28±0.86) (P=0.234). Compared with those in conventional CABG group, patients in MICS group showed longer operation duration [ (5.10±1.09) h vs (4.33±0.86) h], fewer intraoperative blood loss [500 (200, 700) ml vs 700 (600, 900) ml], fewer postoperative 24 h thoracic drainage volume [300 (200, 400) ml vs 400 (250, 500) ml], shorter postoperative ventilation duration [15.0 (12.0, 17.0) h vs 16.5 (12.5, 19.0) h, P<0.001], LOS in ICU [18.0 (15.0, 20.0) h vs 20.0 (16.0, 23.0) h, P<0.001] and total LOS in hospital [(12.6±2.7) d vs (14.5±3.9) d, P<0.001]. MI and PI of graft vessels were similar between the two groups (both P>0.05). Moreover, there were no significant differences in major perioperative complications (i.e., repeat thoracotomy, incision infection, stroke) and mortality between the two groups (all P>0.05). Conclusion: MICS is an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes compared with conventional CABG.
Subject(s)
Coronary Artery Disease , Surgical Wound , Male , Humans , Female , Middle Aged , Aged , Sternotomy , Retrospective Studies , Vascular Surgical Procedures , Arteries , Coronary Artery Disease/surgery , Blood Loss, SurgicalABSTRACT
BACKGROUND: In the PAOLA-1/ENGOT-ov25 primary analysis, maintenance olaparib plus bevacizumab demonstrated a significant progression-free survival (PFS) benefit in newly diagnosed advanced ovarian cancer patients in clinical response after first-line platinum-based chemotherapy plus bevacizumab, irrespective of surgical status. Prespecified, exploratory analyses by molecular biomarker status showed substantial benefit in patients with a BRCA1/BRCA2 mutation (BRCAm) or homologous recombination deficiency (HRD; BRCAm and/or genomic instability). We report the prespecified final overall survival (OS) analysis, including analyses by HRD status. PATIENTS AND METHODS: Patients were randomized 2 : 1 to olaparib (300 mg twice daily; up to 24 months) plus bevacizumab (15 mg/kg every 3 weeks; 15 months total) or placebo plus bevacizumab. Analysis of OS, a key secondary endpoint in hierarchical testing, was planned for â¼60% maturity or 3 years after the primary analysis. RESULTS: After median follow-up of 61.7 and 61.9 months in the olaparib and placebo arms, respectively, median OS was 56.5 versus 51.6 months in the intention-to-treat population [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.76-1.12; P = 0.4118]. Subsequent poly(ADP-ribose) polymerase inhibitor therapy was received by 105 (19.6%) olaparib patients versus 123 (45.7%) placebo patients. In the HRD-positive population, OS was longer with olaparib plus bevacizumab (HR 0.62, 95% CI 0.45-0.85; 5-year OS rate, 65.5% versus 48.4%); at 5 years, updated PFS also showed a higher proportion of olaparib plus bevacizumab patients without relapse (HR 0.41, 95% CI 0.32-0.54; 5-year PFS rate, 46.1% versus 19.2%). Myelodysplastic syndrome, acute myeloid leukemia, aplastic anemia, and new primary malignancy incidence remained low and balanced between arms. CONCLUSIONS: Olaparib plus bevacizumab provided clinically meaningful OS improvement for first-line patients with HRD-positive ovarian cancer. These prespecified exploratory analyses demonstrated improvement despite a high proportion of patients in the placebo arm receiving poly(ADP-ribose) polymerase inhibitors after progression, confirming the combination as one of the standards of care in this setting with the potential to enhance cure.
Subject(s)
Antineoplastic Agents , Ovarian Neoplasms , Humans , Female , Bevacizumab , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Antineoplastic Agents/therapeutic use , Phthalazines , Poly(ADP-ribose) Polymerase Inhibitors , Maintenance ChemotherapyABSTRACT
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Subject(s)
Heart Failure , Non-ST Elevated Myocardial Infarction , Male , Female , Humans , Aged , Natriuretic Peptide, Brain , Simendan/therapeutic use , Heart Failure/drug therapy , Peptide Fragments , Arrhythmias, Cardiac , Biomarkers , PrognosisABSTRACT
Objective: To explore the effect of dormant polyploid giant cancer cells (PGCC) on nasopharyngeal carcinoma (NPC) recurrence and to clarify the role of inhibition of autophagy in inhibiting NPC-PGCC formation and preventing NPC recurrence. Methods: NPC cells-derived PGCC (NPC-PGCC) were induced by paclitaxel (PTX), and the morphology, polyploid characteristics and cell activity of PGCC were identified by light microscopy, immunofluorescence and Live/Dead cell double staining assays. RNA-seq was used to analyze the differentially expressed genes between NPC-PGCC and diploid nasopharyngeal carcinoma cells CNE2. Functional enrichment and pathway annotation analysis of differentially expressed genes were performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). The level of autophagy in NPC-PGCC cells was assessed by Western Blot and transmission electron microscopy analysis. The role of autophagy in the formation of NPC-PGCC and the effect of NPC-PGCC on the recurrence of nasopharyngeal carcinoma were studied using a highly clinically relevant mouse nasopharyngeal carcinoma recurrence model. Statistical analysis was performed using GraphPad Prism 6 and P-values<0.05 were considered statistically significant. Results: NPC-PGCC induced by paclitaxel had the characteristics of burst-like division after dormancy. GO enrichment and KEGG pathway analyses identified the significant biological processes and pathways mainly concentrated in autophagy and related pathways involving the differentially expressed genes between NPC-PGCC and diploid nasopharyngeal carcinoma cells CNE2. The autophagy level was significantly enhanced in NPC-PGCC cells. In a highly clinically relevant mouse nasopharyngeal carcinoma recurrence model, the number of PGCC in the primary tumor of the nude mice treated with cisplatin were higher than those of the other groups. In nude mice pretreated with autophagy inhibitor and then co-treatment with autophagy inhibitor and cisplatin, the number of PGCC in primary tumors was less and the recurrence rate was significantly lower than in other groups. Conclusions: The mechanism of dormant polyploid giant cancer cells formation is related to autophagy. Inhibition of autophagy can inhibit the formation of PGCC and thus prevent the recurrence of nasopharyngeal carcinoma.
Subject(s)
Carcinoma , Nasopharyngeal Neoplasms , Animals , Autophagy , Carcinoma/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cisplatin/pharmacology , Gene Expression Regulation, Neoplastic , Mice , Mice, Nude , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Neoplasms/pathology , Paclitaxel/pharmacology , PolyploidySubject(s)
Extracellular Vesicles , Rhinitis, Allergic , Rhinitis , Sinusitis , Chronic Disease , HumansABSTRACT
Objective: To investigate the relationship between embryo implantation site and adenomyotic lesions in pregnant patients with adenomyosis and its effects on pregnancy outcomes. Methods: Between January 2018 and December 2020, the clinical data of 95 pregnant patients with adenomyosis who were hospitalized in the Women's Hospital, School of Medicine, Zhejiang University, which could identify the implantation site of embryo or placenta (≥11 weeks of pregnancy) through the nuchal translucency test under ultrasonography were analyzed retrospectively. According to the relationship between embryo implantation site and adenomyotic lesions, 95 patients were divided into two groups:short-distance group (n=59, the embryo or placenta implantation was very close to or over the adenomyotic lesion), and long-distance group (n=36, the implantation site of embryo or placenta was far away from the lesion, or the implantation site and the adenomyotic lesion were on different sides of the uterus). Next, taking 28 weeks of pregnancy as cut-off value, 95 patients were divided into <28 weeks of pregnancy group (pregnancy was terminated because of adverse pregnancy outcome before 28 weeks) and ≥28 weeks of pregnancy group (pregnancy lasted to 28 weeks and later), the differences of pregnancy outcomes between the two groups in different gestation times were analyzed. Results: (1) The age of 95 pregnant patients with adenomyosis was (34.8±3.5) years. There were no significant differences with regard to age, uterine size before pregnancy, the proportions of primipara, assisted reproductive technology conception, endometriosis, history of estrogen and progesterone treatment, diffuse adenomyotic lesions between the short-distance group and the long-distance group (all P>0.05). (2) Among the 95 patients, 12 patients (13%, 12/95) had adverse pregnancy outcomes before 28 weeks of pregnancy (i.e. pregnancy <28 weeks), including 11 cases (19%, 11/59) in the short-distance group and 1 case (3%, 1/36) in the long-distance group, there was significant difference between the two groups (χ²=5.100, P=0.027). Among the 11 patients with adverse pregnancy outcomes at <28 weeks of gestation in the short-distance group, 1 case had threatened rupture of uterus before delivery of twin pregnancy at 26 weeks of gestation, 5 cases had intra uterine fetal death in the second trimester of pregnancy, 4 cases had late inevitable abortion, and 1 case had live birth of singleton at 26 weeks of gestation. In the long-distance group, one patient with adverse pregnancy outcome less than 28 weeks of pregnancy was late inevitable abortion. (3) Of the 95 patients, 83 cases were pregnant for ≥28 weeks (48 cases in the short-distance group and 35 cases in the long-distance group), and their final pregnancy outcome was all live birth. Compared with the long-distance group, the incidence of placental abnormalities (60% vs 14%), fetal distress (27% vs 6%), preterm delivery (67% vs 23%) and intrapartum bleeding [median 350 ml (range: 100-1 500 ml) vs 300 ml (range: 100-800 ml)] in the short-distance group were significantly higher (all P<0.05). While the gestational weeks in the short-distance group [median 37 weeks (range: 30-41 weeks) vs 38 weeks (range: 28-41 weeks)] and neonatal birth weight [median 2 790 g (range: 1 170-4 040 g) vs 3 010 g (range: 980-4 320 g)] decreased significantly (all P<0.05), compared with those in the long-distance group. Conclusion: Patients with pregnancy complicated with adenomyosis are prone to adverse pregnancy outcomes if the embryo implantation is located on or very close to adenomyotic lesions, so close monitoring and early intervention should be carried out to improve pregnancy outcomes.
Subject(s)
Adenomyosis , Pregnancy Outcome , Adenomyosis/diagnostic imaging , Adult , Embryo Implantation , Female , Humans , Infant, Newborn , Placenta/diagnostic imaging , Pregnancy , Pregnancy, Twin , Retrospective StudiesABSTRACT
The article "HOXB7 promotes proliferation and metastasis of glioma by regulating the Wnt/ß-catenin pathway, by X.-Y. Huo, X.-Y. Zhang, F. Yuan, X.-Y. Zhao, B.-A. You, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2476-2485-DOI: 10.26355/eurrev_201903_17395-PMID: 30964174" has been withdrawn from the authors who found some errors in the research data. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17395.
ABSTRACT
Objective: To explore the effects of vitamin D3 on intestinal mucosal barrier of mice with severe burns. Methods: Forty-two C57BL/6C male mice aged eight to twelve weeks were divided into vitamin D3 vehicle+ sham injury group of seven mice, vitamin D3 vehicle+ burn injury group of fourteen mice, vitamin D3+ sham injury group of seven mice, and vitamin D3+ burn injury group of fourteen mice according to random number table. Mice in vitamin D3 vehicle+ sham injury group and vitamin D3 vehicle+ burn injury group were injected with vehicle of vitamin D3 at a dose of 0.1 mL intraperitoneally at 1, 24, and 48 h before burn experiment. Mice in vitamin D3+ sham injury group and vitamin D3+ burn injury group were injected with vitamin D3 at a dose of 100 ng/kg dissolved in 0.1 mL vehicle intraperitoneally at the same time points. Mice in vitamin D3 vehicle+ burn injury group and vitamin D3+ burn injury group were inflicted with 30% total body surface area full-thickness dermal scald (hereinafter referred to as burn) on the back by 98 â hot water for 3 to 4 seconds. And mice in vitamin D3 vehicle+ sham injury group and vitamin D3+ sham injury were treated with 37 â water on the back for 3 to 4 seconds to simulate injury. Seven mice in vitamin D3 vehicle+ sham injury group and seven mice in vitamin D3+ sham injury group at post injury hour (PIH) 24, and seven mice in vitamin D3 vehicle+ burn injury group and seven mice in vitamin D3+ burn injury group at PIH 6 and 24 were sacrificed respectively to collect mesentery lymph nodes, spleens, livers, and intestinal tissue. The mesentery lymph nodes, spleens, and livers of mice in each group were collected to observe growth of bacteria, and number of bacteria was counted. Intestinal tissue of mice in each group was collected to detect protein expressions of zonal occludin 1 (ZO-1) and occludin by immunohistochemistry staining method, distribution of ZO-1 by immunofluorescence staining method, and expression of occludin by Western blotting. Data were processed with Kruskal-Wallis H test, Nemenyi test, one-way analysis of variance, t test, and Bonferroni correction. Results: (1) At PIH 6 and 24, bacterial counts of mesentery lymph nodes, livers, and spleens of mice in vitamin D3 vehicle+ burn injury group were significantly higher than those of mice in vitamin D3 vehicle+ sham injury group (P<0.05). At PIH 6, bacterial counts of livers and spleens of mice in vitamin D3+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ burn injury group (P<0.05). At PIH 24, bacterial counts of mesentery lymph nodes and livers of mice in vitamin D3+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ burn injury group (P<0.05). (2) At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were significantly lower than those of mice in vitamin D3 vehicle+ sham injury group, and expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3+ burn injury group were close to those of mice in vitamin D3+ sham injury group. At PIH 6 and 24, expressions of ZO-1 and occludin of intestinal tissue of mice in vitamin D3+ burn injury group were significantly higher than those of mice in vitamin D3 vehicle+ burn injury group. (3) At PIH 6 and 24, compared with that of mice in vitamin D3 vehicle+ sham injury group, distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3 vehicle+ burn injury group was discontinuous. Distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3+ sham injury group was normal, and the distribution of ZO-1 of intestinal mucosal epithelium of mice in vitamin D3+ burn injury group was with good continuity. (4) At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were 0.720±0.003, 0.638±0.052 respectively, significantly lower than 0.918±0.003 of mice in vitamin D3 vehicle+ sham injury group (t=57.33, 5.36, P<0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3+ burn injury group were 0.994±0.058, 1.064±0.060, close to 0.938±0.023 of mice in vitamin D3+ sham injury group (t=0.91, 1.96, P>0.05). At PIH 6 and 24, expressions of occludin of intestinal tissue of mice in vitamin D3 vehicle+ burn injury group were significantly lower than those of mice in vitamin D3+ burn injury group (t=4.75, 5.35, P<0.05). Conclusions: Intestinal bacterial translocation can occur in the early stage of severe burn. And vitamin D3 plays a protective role in the intestinal mucosal barrier post severe burn to reduce the bacterial translocation by protecting tight junction proteins of intestinal epithelium.
Subject(s)
Burns , Cholecalciferol/pharmacology , Intestinal Mucosa/drug effects , Animals , Cholecalciferol/administration & dosage , Male , Mice , Mice, Inbred C57BL , Rats , Rats, Sprague-DawleyABSTRACT
OBJECTIVE: The purpose of this study was to investigate the expression level of HOXB7 in gliomas and its effect on the proliferation and metastasis of gliomas, as well as its regulatory mechanism of promoting the malignant progression of glioma. PATIENTS AND METHODS: In this study, 32 pairs of glioma tumor tissue specimens and adjacent ones were collected and the HOXB7 expression levels in these tissues were detected using quantitative Real Time Polymerase Chain Reaction (qRT-PCR), and the interplay between HOXB7 level and clinical parameters of glioma was analyzed. QRT-PCR was used to further verify the expression of HOXB7 in glioma cell lines. The sh-HOXB7 knockdown model was constructed in glioma cell lines, and the influence of HOXB7 on the biological function of glioma cells was examined by Cell Counting Kit-8 (CCK-8) and transwell assay. Meanwhile, Western blot was applied to explore whether HOXB7 can promote the progression of glioma through the Wnt/ ß-catenin pathway. RESULTS: QRT-PCR results showed that the level of HOXB7 in glioma tumor tissue specimens was conspicuously higher than that in the adjacent normal ones. The occurrence of lymph node or distant metastasis was higher and the prognosis was worse in patients with higher HOXB7 expression. In addition, compared with the sh-NC group, cell proliferation, invasiveness and migration ability of the sh-HOXB7 group decreased conspicuously. Subsequently, the Western blot result revealed that the expression of key proteins in the Wnt/ß-catenin signaling pathway was conspicuously reduced in the sh-HOXB7 group, thereby promoting the malignant progression of glioma. CONCLUSIONS: HOXB7 may promote the invasiveness and migration of glioma cells via regulating the Wnt/ß-catenin signaling pathway, and is conspicuously associated with lymph node or distant metastasis and poor prognosis.
Subject(s)
Brain Neoplasms/pathology , Glioma/pathology , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Up-Regulation , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Female , Gene Expression Regulation, Neoplastic , Glioma/genetics , Glioma/metabolism , Humans , Lymphatic Metastasis , Male , Prognosis , Survival Analysis , Wnt Signaling PathwayABSTRACT
Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).
Subject(s)
Fallopian Tube Neoplasms/surgery , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Bevacizumab/therapeutic use , Carboplatin/therapeutic use , Chemotherapy, Adjuvant , Fallopian Tube Neoplasms/drug therapy , Female , Fertility Preservation , France , Humans , Hyperthermia, Induced , Ovarian Neoplasms/drug therapy , Paclitaxel/therapeutic use , Peritoneal Neoplasms/drug therapyABSTRACT
An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). For FIGO stages III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancer (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B).
Subject(s)
Fallopian Tube Neoplasms/diagnosis , Fallopian Tube Neoplasms/surgery , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/surgery , Biomarkers, Tumor/blood , Fallopian Tube Neoplasms/pathology , Female , France , Humans , Laparoscopy , Magnetic Resonance Imaging , Minimally Invasive Surgical Procedures , Neoplasm Metastasis , Neoplasm Staging , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/pathology , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/pathology , Perioperative Care , Peritoneal Neoplasms/pathology , Tomography, X-Ray ComputedABSTRACT
An MRI is recommended for an ovarian mass that is indeterminate on ultrasound. The ROMA score (combining CA125 and HE4) can also be calculated (Grade A). In presumed early-stage ovarian or tubal cancers, the following procedures should be performed: an omentectomy (at a minimum, infracolic), an appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C), and pelvic and para-aortic lymphadenectomies (Grade B) for all histologic types, except the expansile mucinous subtypes, for which lymphadenectomies can be omitted (grade C). Minimally invasive surgery is recommended for early-stage ovarian cancer, when there is no risk of tumor rupture (grade B). Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). For FIGO stage III or IV ovarian, tubal, and primary peritoneal cancers, a contrast-enhanced computed tomography (CT) scan of the thorax/abdomen/pelvis is recommended (Grade B), as well as laparoscopic exploration to take multiple biopsies (grade A) and a carcinomatosis score (Fagotti score at a minimum) (grade C) to assess the possibility of complete surgery (i.e., leaving no macroscopic tumor residue). Complete surgery by a midline laparotomy is recommended for advanced ovarian, tubal, or primary peritoneal cancers (grade B). For advanced cancers, para-aortic and pelvic lymphadenectomies are recommended when metastatic adenopathy is clinically or radiologically suspected (grade B). When adenopathy is not suspected and when complete peritoneal surgery is performed as the initial surgery for advanced cancer, the lymphadenectomies can be omitted because they do not modify either the medical treatment or overall survival (grade B). Primary surgery (before other treatment) is recommended whenever it appears possible to leave no tumor residue (grade B). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III disease, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).
Subject(s)
Carcinoma/therapy , Fallopian Tube Neoplasms/therapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Carcinoma/diagnosis , Carcinoma/pathology , Fallopian Tube Neoplasms/diagnosis , Fallopian Tube Neoplasms/pathology , Female , France , Humans , Minimally Invasive Surgical Procedures , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/diagnosis , Peritoneal Neoplasms/pathologyABSTRACT
BACKGROUND: Antitumor activity of molecular-targeted agents is guided by the presence of documented genomic alteration in specific histological subtypes. We aim to explore the feasibility, efficacy and therapeutic impact of molecular profiling in routine setting. PATIENTS AND METHODS: This multicentric prospective study enrolled adult or pediatric patients with solid or hematological advanced cancer previously treated in advanced/metastatic setting and noneligible to curative treatment. Each molecular profile was established on tumor, relapse or biopsies, and reviewed by a molecular tumor board (MTB) to identify molecular-based recommended therapies (MBRT). The main outcome was to assess the incidence rate of genomic mutations in routine setting, across specific histological types. Secondary objectives included a description of patients with actionable alterations and for whom MBRT was initiated, and overall response rate. RESULTS: Four centers included 2579 patients from February 2013 to February 2017, and the MTB reviewed the molecular profiles achieved for 1980 (76.8%) patients. The most frequently altered genes were CDKN2A (N = 181, 7%), KRAS (N = 177, 7%), PIK3CA (N = 185, 7%), and CCND1 (N = 104, 4%). An MBRT was recommended for 699/2579 patients (27%), and only 163/2579 patients (6%) received at least one MBRT. Out of the 182 lines of MBRT initiated, 23 (13%) partial responses were observed. However, only 0.9% of the whole cohort experienced an objective response. CONCLUSION: An MBRT was provided for 27% of patients in our study, but only 6% of patients actually received matched therapy with an overall response rate of 0.9%. Molecular screening should not be used at present to guide decision-making in routine clinical practice outside of clinical trials.This trial is registered with ClinicalTrials.gov, number NCT01774409.
Subject(s)
Mutation , Neoplasm Recurrence, Local/diagnosis , Neoplasms/diagnosis , Adult , Biomarkers, Tumor/genetics , Child , Databases, Genetic , Early Detection of Cancer/methods , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathology , Precision Medicine/methods , Prospective StudiesABSTRACT
Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).
Subject(s)
Carcinoma, Ovarian Epithelial/therapy , Ovarian Neoplasms/therapy , Age Factors , Biomarkers, Tumor/analysis , Carcinoma, Ovarian Epithelial/pathology , Chemotherapy, Adjuvant , Continuity of Patient Care , Fallopian Tube Neoplasms/pathology , Fallopian Tube Neoplasms/therapy , Female , Fertility Preservation , France , Humans , Hyperthermia, Induced , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Societies, MedicalABSTRACT
Medical treatment of ovarian cancer is based on chemotherapy. Most patients, regardless of the initial stage of their disease, will need to be treated (grade A). Standard treatment relies on a carboplatin and paclitaxel combination (grade A). For advanced diseases (stage I-IIA1 or IIIB à IV), the addition of an antiangiogenic treatment with bevacizumab to the chemotherapy, followed by a maintenance for 15 months should be proposed as it allows better disease control (grade A). For patients with somatic or germline BRCA mutations and disease stage III or IV, olaparib is recommended as maintenance treatment for 24 months (grade B, but olaparib had not the French approval as first-line treatment at the time of the present recommendation editing). No other targeted therapy or immunotherapy has yet been proven effective at the initial phase of ovarian cancer treatment. The treatment of rare tumors with a special histology must be discussed in a specialized multidisciplinary meeting of the network of rare malignant tumors of the ovary (TMRO) labeled by the INCa.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ovarian Epithelial/drug therapy , Ovarian Neoplasms/drug therapy , Algorithms , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Ovarian Epithelial/mortality , Carcinoma, Ovarian Epithelial/pathology , Drug Administration Schedule , Female , France , Humans , Indoles/administration & dosage , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Oxaliplatin/administration & dosage , Paclitaxel/administration & dosage , Phthalazines/administration & dosage , Piperazines/administration & dosage , Societies, MedicalABSTRACT
The Esophageal Cancer Committee of the Chinese Anti-Cancer Association have released ãChinese expert consensus on mediastinal lymph node dissection in esophagectomy for esophageal cancer (2017 edition)ã. This consensus provides guidance to standardize mediastinal lymph node dissection in esophagectomy for esophageal cancer in China, and represents the first Chinese version of naming and grouping mediastinal lymph nodes for esophageal cancer. However, controversies exist in N staging. The aim of this article is to discuss whether N staging should base on the number of lymph node metastases, or base on the region in which the metastatic lymph nodes are located.