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BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
Frontiers in Oncology 2022Invasive moles are a subtype of gestational trophoblastic neoplasia (GTN) that usually develops after hydatidiform molar pregnancies. Uterine rupture in high-risk GTN is...
BACKGROUND
Invasive moles are a subtype of gestational trophoblastic neoplasia (GTN) that usually develops after hydatidiform molar pregnancies. Uterine rupture in high-risk GTN is a rare and potentially catastrophic event. The treatment of invasive mole perforation with uterine rupture is particularly challenging in young women who desire fertility preservation.
CASE PRESENTATION
We present the case of a 22-year-old woman with a rapidly transformed invasive mole after two evacuations for a complete molar pregnancy. Within 21 days of the second molar evacuation, the serum β-hCG level surged from 5,718 mIU/ml to 444,617 mIU/ml. An ultrasonography examination showed the uterus was 9.2×8.9×7.8 cm in size with an uneven echo area of 6.9×5.2 cm near the fundus of the uterine cavity; the convex anterior wall had no normal muscle layer, and the outer margin was about 0.24 cm from the serosal layer. The patient was diagnosed with an invasive mole. Since she desired fertility preservation, we proposed a methotrexate (MTX) chemotherapy regimen. Before the planned chemotherapy, she experienced sudden abdominal pain accompanied by a blood pressure of 76/48 mmHg and a pulse rate of 116 bpm. An emergency abdominal ultrasound scan showed acute intra-abdominal bleeding (approximately 2,000 ml), and blood tests showed a hemoglobin concentration of 7.9 g/dL. Immediate uterine artery embolization was performed, and 35 mg MTX was administered bilaterally through the uterine arteries. The next day, the serum β-hCG decreased to 83,530 mIU/ml, and the vital signs remained stable. Seven days later, the patient received a combination of etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO), and the serum β-hCG level normalized after cycle five. At the 13-month follow-up after therapy completion, the woman was disease-free with a normal β-hCG level.
CONCLUSION
Our experience highlights the potential feasibility and efficacy of conservative treatment for fertility preservation in such scenarios.
PubMed: 36561530
DOI: 10.3389/fonc.2022.1019082 -
Journal of Medical Case Reports Dec 2022Paratesticular rhabdomyosarcoma is a rare and aggressive mesenchymal tumor, accounting for only 7% of all rhabdomyosarcomas. It is mainly encountered in children and...
INTRODUCTION
Paratesticular rhabdomyosarcoma is a rare and aggressive mesenchymal tumor, accounting for only 7% of all rhabdomyosarcomas. It is mainly encountered in children and adolescents. The standard treatment consists of radical orchidectomy with negative surgical margins. However, chemotherapy is recommended to control retroperitoneal micrometastasis. The place of surgery for progressive retroperitoneal lymph node metastases remains controversial. We present a case of paratesticular rhabdomyosarcoma with progressive retroperitoneal lymph node metastases treated with surgery.
CASE REPORT
We report a case of a 17-year-old North African male with no particular medical history who presented with a left scrotal mass that had been evolving for several months. Beta-human chorionic gonadotropin, alpha-fetoprotein, and lactate dehydrogenase were normal. Scrotal ultrasonography revealed the presence of a 6 cm heterogeneous hypoechogenic tissular mass with cystic areas adherent to the left scrotal wall, which was thickened in some places and vascularized by color Doppler. It exerted a mass effect on the homolateral testicle, which was of average volume. The thoracic-abdominal-pelvic computed tomography scan showed the presence of suspicious paraaortic lymph nodes. The most voluminous one measured 16 × 23 mm. A left orchidectomy was performed. The final pathology report revealed an 8 cm paratesticular rhabdomyosarcoma of the embryonic type that displaced the testicle without invading it. Without going beyond it, it infiltrated the epididymis, the rete testis, and the albuginea. The surgical margin at the level of the spermatic cord was free. The patient had adjuvant chemotherapy (ifosfamide, vincristine, and dactinomycin). The patient had a challenging paraaortic lymph node dissection since the mass enlaced the left ureter and renal vessels. On histological examination, the paraaortic lymph nodes were metastatic.
CONCLUSION
Rhabdomyosarcoma is an aggressive malignancy with high metastatic potential. Therefore, only an accurate diagnosis and early treatment can ensure better survival. Surgery in expert hands seems to be a good option for progressive retroperitoneal nodes. However, further studies are needed to determine the place of surgery in this setting.
Topics: Child; Adolescent; Humans; Male; Testicular Neoplasms; Lymphatic Metastasis; Rhabdomyosarcoma; Orchiectomy
PubMed: 36550579
DOI: 10.1186/s13256-022-03707-x -
Gynecologic Oncology Feb 2023Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus...
BACKGROUND
Single-agent methotrexate (MTX) is commonly used as first-line treatment for low-risk gestational trophoblastic neoplasia (LR-GTN), although no international consensus exists on the optimal treatment regimen to maximise complete hCG response (CR) and minimise relapse rates. Current regimens differ in the route of administration, dose scheduling, and use of flat-dose, body surface area (BSA)- or weight-based dosing. In the UK a methotrexate-folinic acid (MTX-FA) 8-day 50 mg intramuscular flat-dose regimen is used, with 15 mg oral folinic acid rescue. In LR-GTN patients, we aim to determine the effect of MTX dose adjustment by BSA and weight upon chemotherapy response and disease relapse.
METHODS
Between January 1973 and August 2020, 935 LR-GTN patients treated with first-line MTX-FA were identified from a single UK specialist trophoblastic centre. Of these, 364 were included, of which 178 (49%) had a CR to first-line MTX-FA. Subgroup analyses were performed upon: (i) patients who changed chemotherapy due to MTX toxicity (n = 33); and (ii) patients with a FIGO score of 5-6 (n = 85). Logistic regression analysis explored the relationship between BSA or weight adjusted MTX dosing and: (i) CR to first-line chemotherapy; (ii) incidence of disease relapse. Linear regression analyses assessed the correlation of BSA and weight with the number of MTX-FA cycles required to achieve CR.
RESULTS
In LR-GTN patients, BSA and weight adjusted MTX-FA dosing did not influence CR to first-line chemotherapy or the incidence of disease relapse. The number of MTX cycles required to achieve CR was not associated with BSA or weight. These findings were maintained in a subgroup analysis of FIGO 5-6 patients. The incidence of MTX toxicity was not influenced by BSA or weight.
CONCLUSIONS
In the treatment of LR-GTN, dose individualisation using BSA or weight is not required, and fixed dosing continues to be preferred as the UK standard.
Topics: Pregnancy; Female; Humans; Methotrexate; Leucovorin; Body Surface Area; Retrospective Studies; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Drug-Related Side Effects and Adverse Reactions; Dactinomycin
PubMed: 36495594
DOI: 10.1016/j.ygyno.2022.11.025 -
Medicine Nov 20225-Fluorouracil (5-FU) and actinomycin D (ActD) are often used in chemotherapy for various cancers. Side effects are more common in bone marrow suppression, liver... (Review)
Review
RATIONALE
5-Fluorouracil (5-FU) and actinomycin D (ActD) are often used in chemotherapy for various cancers. Side effects are more common in bone marrow suppression, liver function impairment, and gastrointestinal responses. Skin effects are rare and easy to be ignored by doctors and patients, which can lead to life-threatening consequence.
PATIENT CONCERNS
We reported a 45-year-old woman patient developed skin erythema and fingernail belt in chemotherapy of 5-FU and ActD.
DIAGNOSIS
Erythema multiforme drug eruption.
INTERVENTIONS
Laboratory tests including blood and urine routine, liver and kidney function, electrolytes and coagulation function and close observation.
OUTCOMES
The rash was gone and the nail change returned.
LESSONS
Delays in diagnosis or treatment may lead to serious consequence. We should pay attention to the dosage of 5-FU and ActD, monitor adverse reactions strictly, to reduce occurrence of skin malignant events.
Topics: Female; Pregnancy; Humans; Middle Aged; Dactinomycin; Hydatidiform Mole, Invasive; Fluorouracil; Erythema Multiforme; Drug Eruptions; Uterine Neoplasms
PubMed: 36451432
DOI: 10.1097/MD.0000000000031678 -
BMC Pediatrics Oct 2022Idiopathic connective tissue disease juvenile dermatomyositis (JDM) is characterised by inflammatory myositis and distinctive skin abnormalities. Only a few cases of...
BACKGROUND
Idiopathic connective tissue disease juvenile dermatomyositis (JDM) is characterised by inflammatory myositis and distinctive skin abnormalities. Only a few cases of Dermatomyositis (DM) owing to chemotherapy used to treat cancer have been reported, despite the fact that the link between DM and cancer in adults is widely known. We describe the case of a female, age 14, who experienced DM as a side effect of chemotherapy following enucleation for retinoblastoma. We also discussed our patient's likely pathophysiology of JDM after treatment.
CASE PRESENTATION
A 14-year-old female came to our facility complaining of trouble walking and bluish-black discoloration on her neck, elbows, forehead, and knees that had been present for eight months. The patient had undergone enucleation of the left eye due to retinoblastoma, followed by 40 cycles of radiation therapy and 13 cycles of chemotherapy with Cyclophosphamide, Etoposide, Carboplatin, Vincristine, and Dactinomycin. Her serum LDH and CPK levels were high, and she tested positive for ANA. The muscle biopsy was consistent with the changes of DM. When electromyography was performed, it revealed tiny, fibrillating, polyphasic motor unit potentials and sharp, positive waves that were suggestive with DM. A diagnosis of JDM was made after taking into account the symptoms, biochemical data, muscle biopsy, and electromyography results. The patient's symptoms started to get better once methotrexate and oral corticosteroids were started.
CONCLUSION
This case report emphasises the value of ongoing observation after cancer chemotherapy because specific cutaneous and muscle symptoms may lead paediatricians to consider the possibility of chemotherapy-induced JDM, which is uncommon in young patients.
Topics: Adult; Humans; Female; Adolescent; Dermatomyositis; Retinoblastoma; Electromyography; Retinal Neoplasms; Antineoplastic Agents
PubMed: 36316673
DOI: 10.1186/s12887-022-03704-5 -
Pediatrics Nov 2022We aimed to clinically characterize the health, neurocognitive, and physical function outcomes of curative treatment of Wilms tumor.
OBJECTIVES
We aimed to clinically characterize the health, neurocognitive, and physical function outcomes of curative treatment of Wilms tumor.
METHODS
Survivors of Wilms tumor (n = 280) participating in the St. Jude Lifetime Cohort, a retrospective study with prospective follow-up of individuals treated for childhood cancer at St. Jude Children's Research Hospital, were clinically evaluated and compared to age and sex-matched controls (n = 625). Health conditions were graded per a modified version of the National Cancer Institute's Common Terminology Criteria for Adverse Events. Standardized neurocognitive testing was graded by using age-adjusted z-scores. Impaired physical function was defined by age- and sex-matched z-scores >1.5 SD below controls. Modified Poisson regression was used to compare the prevalence of conditions and multivariable logistic regression to examine treatment associations.
RESULTS
Median age at evaluation was similar between survivors and controls (30.5 years [9.0-58.0] and 31.0 [12.0-70.0]). Therapies included nephrectomy (100%), vincristine (99.3%), dactinomycin (97.9%), doxorubicin (66.8%), and abdominal (59.3%) and/or chest radiation (25.0%). By age 40 years, survivors averaged 12.7 (95% confidence interval [CI] 11.7-13.8) grade 1-4 and 7.5 (CI: 6.7-8.2) grade 2 to 4 health conditions, compared to 4.2 (CI: 3.9-4.6) and 2.3 (CI: 2.1-2.5), respectively, among controls. Grade 2 to 4 endocrine (53.9%), cardiovascular (26.4%), pulmonary (18.2%), neurologic (8.6%), neoplastic (7.9%), and kidney (7.2%) conditions were most prevalent. Survivors exhibited neurocognitive and physical performance impairments.
CONCLUSIONS
Wilms tumor survivors experience a threefold higher burden of chronic health conditions compared to controls and late neurocognitive and physical function deficits. Individualized clinical management, counseling, and surveillance may improve long-term health maintenance.
Topics: Child; Humans; Adult; Retrospective Studies; Prospective Studies; Survivors; Wilms Tumor; Chronic Disease; Kidney Neoplasms; Outcome Assessment, Health Care
PubMed: 36300342
DOI: 10.1542/peds.2022-056918 -
Disease Markers 2022Macrophages are heterogeneous cells that can be polarized into M1 or M2 phenotype. mA "reader" YTH domain family protein 2 (YTHDF2) has been the mA binding protein with...
Macrophages are heterogeneous cells that can be polarized into M1 or M2 phenotype. mA "reader" YTH domain family protein 2 (YTHDF2) has been the mA binding protein with the highest activity, which can recognize and disturb mA-containing mRNA in processing bodies to reduce mRNA stability. YTHDF2 is recently identified as an effective RNA binding protein that modulates inflammatory gene levels within inflammatory responses. However, the role of YTHDF2 in M1/M2 macrophage polarization has not been reported. We established a M1/M2 macrophage polarization model using bone-marrow-derived macrophages and found that the expression levels of YTHDF2 in M1/M2 macrophages were both elevated. YTHDF2-knockdown macrophage polarization model was then established, and through qPCR, ELISA, and FACS, we discovered that suppressing YTHDF2 encouraged M1 polarization but restrained M2 polarization. In M1 macrophages, YTHDF2 silencing had no significant effect on p53 expression; however, in YTHDF2 knockdown, M2 macrophage p53 expression was remarkably upregulated. p53 inhibitor PFT- was then applied and revealed that suppressing p53 simultaneously promoted YTHDF2-silenced M1 polarization and facilitated M2 macrophage polarization. Actinomycin D assays were further utilized to examine the mRNA degradation level of different cytokines, and p53 mRNA degradation in YTHDF2-depleted M2 cells was discovered impeded. Western Blot analysis also implied that a deficit in YTHDF2 expression may activate MAPK and NF-B pathways. In this study, YTHDF2 induces M2 macrophage polarization by promoting the degradation of p53 mRNA. YTHDF2 suppresses M1 macrophage polarization by inhibiting NF-B, p38, and JNK signaling pathways, yet p53 remains unaffected in YTHDF2-silenced M1 macrophages.
Topics: NF-kappa B; Tumor Suppressor Protein p53; Dactinomycin; Signal Transduction; Macrophages; Cytokines; RNA-Binding Proteins; RNA, Messenger
PubMed: 36277978
DOI: 10.1155/2022/3153362 -
International Journal of Cancer Apr 2023In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a... (Randomized Controlled Trial)
Randomized Controlled Trial
Late toxicity comparison of alkylating-based maintenance regimen with cyclophosphamide (VAC) vs ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro-EWING99-R1 in France.
In Euro-EWING99-R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard-risk Ewing sarcoma (SR-EWS) after a common induction with VIDE (vincristine-ifosfamide-doxorubicin-etoposide). We present the results of the late effects analysis of VAC (vincristine-dactinomycin-cyclophoshamide) vs VAI (vincristine-dactinomycin-ifosfamide) conducted in Euro-EWING99-R1 French cohort. Of 267 French randomized patients, 204 were alive and free-of-relapse at 5-years including 172 with available long-term follow-up data concerning cardiac, renal and/or gonadal functions (sex-ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m , ifosfamide = 59.4 g/m ) and 88 in VAI (ifosfamide = 97.1 g/m ). With a median follow-up of 10 years (range = 5-17), five late relapses and five second malignancies were recorded. The 10-year event-free survival among 5-year free-of-relapse survivors was similar between VAC and VAI (93% vs 95%, P = .63). We estimated the 10-year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%-7.6%) and 34.8% (95% CI = 26.8%-42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P = .02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P < .01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro-EWING99-R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE-VAC or VDC/IE (vincristine-doxorubicin-cyclophoshamide/ifosfamide-etoposide).
Topics: Male; Humans; Female; Adolescent; Sarcoma, Ewing; Ifosfamide; Dactinomycin; Vincristine; Etoposide; Bone Neoplasms; Neoplasm Recurrence, Local; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; France
PubMed: 36250317
DOI: 10.1002/ijc.34326 -
Polish Journal of Microbiology Sep 2022Whole-genome sequencing and genome mining are recently considered an efficient approach to shine more light on the underlying secondary metabolites of . The present...
Whole-genome sequencing and genome mining are recently considered an efficient approach to shine more light on the underlying secondary metabolites of . The present study unearths the biosynthetic potential of endophytic SX6 as a promising source of biologically active substances and plant-derived compounds for the first time. Out of 38 isolates associated with (L.) Blanco, SX6 was highly active against ATCC® 9027™ and methicillin-resistant (MRSE) ATCC® 35984™. Additionally, SX6 culture extract showed strong cytotoxicity against Hep3B, MCF-7, and A549 cell lines at a concentration of 30 μg/ml, but not in non-cancerous HEK-293 cells. The genome contained 7.69 Mb in size with an average G + C content of 72.8% and consisted of 6,779 protein-coding genes. AntiSMASH analysis resulted in the identification of 29 biosynthetic gene clusters (BGCs) for secondary metabolites. Among them, 4 BGCs showed low similarity (28-67% of genes show similarity) to actinomycin, streptovaricin, and polyoxypeptin gene clusters, possibly attributed to antibacterial and anticancer activities observed. In addition, the complete biosynthetic pathways of plant-derived compounds, including daidzein and genistein were identified using genome mining and HPLC-DAD-MS analysis. These findings portray an exciting avenue for future characterization of promising secondary metabolites from mangrove endophytic .
Topics: Anti-Bacterial Agents; Dactinomycin; Genistein; HEK293 Cells; Humans; Methicillin-Resistant Staphylococcus aureus; Phytochemicals; Primulaceae; Streptomyces; Streptovaricin
PubMed: 36185028
DOI: 10.33073/pjm-2022-034