Re-irradiation for high-grade gliomas:Has anything changed?

Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,published experience,and a better radiobiological knowledge of brain tissue have positioned re-irradiation(re-RT)as an option for many of these patients.Decisions must be individualized,taking into account the pattern of relapse,previous treatment,and functional status,as well as the patient’s preferences and expected quality of life.Many questions remain unanswered with respect to re-RT:Who is the most appropriate candidate,which dose and fractionation are most effective,how to define the target volume,which imaging technique is best for planning,and what is the optimal timing?This review will focus on describing the most relevant studies that include re-RT as salvage therapy,with the aim of simplifying decision-making and designing the best available therapeutic strategy.

Relationship between FGF12 expression in high-grade gliomas and clinical features

Objective:gliomas are the most common intracranial tumors.Fibroblast growth factor-12(FGF12),which belongs to the fibroblast growth factor(FGFs)family,plays an important role in cell mitosis,as well as in other life functions,such as embryo development,tissue repair,cell proliferation,and tumor growth and invasion.The purpose of this study was to explore the potential value of FGF12 in high-grade gliomas and to predict its drug sensitivity.To provide a possible therapeutic target for glioma.Methods:high-grade glioma gene expression data and clinical information were downloaded from the gene expression omnibus(GEO)database,using the R language“impute”and“survival”survival analysis package.The FGF12 genes closely related to survival were screened,a survival curve was drawn,and clinical correlation analysis was conducted.The differentially expressed genes(DEGs)were defined as |logFC|>1,adj.PVal<0.05 as the standard.We used the David for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,and constructed the protein-protein interactions(PPI)network.Then we used the Connectivity Map(CMAP)database for drug location,and the validation group was verified by the Chinese Glioma Genome Atlas(CGGA)database in the same way.Results:we found that high FGF12 expression was associated with a higher survival rate.The same validation was performed in the validation group through the CGGA database,and the survival curve showed the same trend.The expression level of FGF12 is an independent factor that affects the life time and status of the samples,and it is a low risk factor.GO enrichment analysis showed that differential genes were enriched in matrix transmembrane transporter activity,ion channels and calcium ion active channels.KEGG showed that DEGs were enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,dopaminergic synapse and cyclic adenosine monophosphate(cAMP)signaling pathway.Four seed genes,GRIA2,COLLA2,GRIA4 and HES6,were obtained by PPI network analysis.The cAMP was used to analyze and obtained 7 small molecule drugs,such as merbromin,naloxone,AH-2384&ticarcillin,vincamine,amoxicillin,azacyclonol,which may be helpful in the prognosis of high-grade gliomas.Conclusion:FGF12 and its pathway may serve as a biomarker or therapeutic target for high-grade gliomas.

Radiotherapy of high-grade gliomas: current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches

The current standards in radiotherapy of high-grade gliomas(HGG) are based on anatomic imaging techniques, usually computed tomography(CT) scanning and magnetic resonance imaging(MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma(AG) or a grade 4 glioblastoma multiforme(GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume(GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume(CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase(CTV1) including any T2 hyperintensity area(edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in < 10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators(LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density(diffusion MRI), angiogenesis(perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography(PET) and magnetic resonance spectroscopy(MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non- contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost(SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines(and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images(PET-MRI machines), the combination of complementary imaging tools(perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.

High-grade gliomas: reality and hopes

In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer(EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem.

Molecular biology of high-grade gliomas: what should the clinician know?

The current World Health Organization classification system of primary brain tumors is solely based on morphologic criteria. However, there is accumulating evidence that tumors with similar histology have distinct molecular signatures that significantly impact treatment response and survival. Recent practice-changing clinical trials have defined a role for routine assessment of O-6-methylguanine-DNA methyltransferase(MGMT) promoter methylation in glioblastoma patients, especially in the elderly, and 1p and 19q codeletions in patients with anaplastic glial tumors. Recently discovered molecular alterations including mutations in IDH-1/2, epidermal growth factor receptor(EGFR), and BRAF also have the potential to become targets for future drug development. This article aims to summarize current knowledge on the molecular biology of high-grade gliomas relevant to daily practice.

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with High-Grade Glioma. Final Report (Protocol BT-06), and Review of Recent Trials

Standard treatment for high-grade glioma involves surgical resection followed by radiation therapy and temozolomide. Unfortunately, there are no standard treatment recommendations after recurrence and new therapies are needed for patients whose tumor recurs after first-line treatment. This single-arm, two-stage, interventional Phase II study evaluated the efficacy and safety of a combination of antineoplastons A10 and AS2-1. Nineteen patients were enrolled in the study (safety population), but fifteen patients with a median age of 9.4 years who met eligibility criteria were evaluated. The majority of subjects (12/15) were Caucasian and 8/15 (53%) were female. More than half (53%) of patients were diagnosed with glioblastoma and 33% with anaplastic astrocytoma. All patients had failed standard therapy including surgery, radiation, and chemotherapy. Antineoplastons were administered intravenously every four hours (median dose of A10 6.9 g/kg/d and AS2-1 0.30 g/kg/d) until objective response was documented and thereafter for a further 8 months. Clinical evaluations were performed every 8 weeks. All patients enrolled in the study were included in the safety analysis but only patients fulfilling the inclusion criteria were included in the efficacy evaluation. The duration of treatment with antineoplastons ranged from 2 weeks to 120 weeks. A complete response was documented in 2/15 (13%), partial response in 2/15 (13%), stable disease in 3/15 (20%). Progression-free survival at six months was 47% and overall survival (OS) at one year was 33.3%. One patient (6.7%) survived 10 years from treatment start. A small group of patients suffered reversible Grade 3 and 4 toxicities including hypernatremia 2/19 (11%) and decrease of neutrophils 1/19 (5%). There were no chronic toxicities. There was improvement of quality of life in patients who had objective response. It is concluded that antineoplastons show efficacy with an acceptable profile in this cohort of patients with recurrent high-grade glioma.

PhaseⅠstudy of chlorogenic acid injection for recurrent high-grade glioma with long-term follow-up

Objective:This study was aimed at analyzing the efficacy and safety of an injectable form of chlorogenic acid(CGA)in patients with recurrent high-grade glioma after standard of care treatments,through a first-in-human,open-label,dose-escalation phase I trial.Methods:A total of 26 eligible patients were enrolled,received intramuscular CGA injections at 5 dose levels,and were followed up for 5 years.CGA was well tolerated,and the maximum tolerated dose was 5.5 mg/kg.Results:The most common treatment-related adverse events occurred at the sites of injection.No grade 3 or 4 adverse events(e.g.,drug allergy)were reported for these patients except for induration at the injection sites.A clinical pharmacokinetic study showed that CGA was rapidly eliminated from the plasma,with a t_(1/2)of 0.95–1.27 h on day 1 and 1.19–1.39 h on day 30,and no detectable CGA was observed on days 9,11,13,23,25,27,and 29 before CGA administration.After the first treatment cycle,52.2%of patients(12 of 23)achieved stable disease.Long-term follow-up indicated an estimated median overall survival of 11.3 months for all 23 evaluable patients.Of the 18 patients with grade 3 glioma,the median overall survival was 9.5 months.Two patients remained alive at the cutoff day.Conclusions:This phase I study demonstrated that CGA has a favorable safety profile(with no severe toxicity),and provides preliminary clinical benefits for patients with high grade glioma relapsing after prior standard therapies,thus shedding light on the potential clinical application of CGA for recurrent grade 4 glioma.

Magnetic Resonance Perfusion Imaging in the Diagnosis of High-Grade Glioma Progression and Treatment-Related Changes: A Systematic Review

In patients with high grade gliomas (HGGs), progression after treatment can be difficult to diagnose due to treatment-related effects, which overlap in appearance with tumour progression on conventional magnetic resonance imaging (MRI) sequences. Specialised imaging methods have been studied for this purpose, though most institutions currently use histopathology or clinicoradiological follow-up for diagnosis. This publication aims to review the evidence for perfusion MRI techniques. The databases of Pubmed, MEDLINE, EMBASE and Scopus were searched using combinations of the subject headings high grade glioma and MRI perfusion. 41 articles fulfilled the inclusion criteria. Dynamic Susceptibility Contrast (DSC) MRI was the most extensively studied, with several studies achieving high sensitivities and specificities. Other techniques exhibiting potential include Dynamic Contrast Enhanced (DCE) MRI, Arterial Spin Labelling (ASL). However, these techniques are not widely used or available for clinical practice. Composite measures combining results from multiple techniques tended to achieve higher accuracies. Some publications compared processing software used or looked at machine learning with relative success. An issue common to the literature is the lack of standardisation in the reference standard and acquisition/processing methods. Furthermore, many had small sample sizes, and further consideration needs to be given with regards to timing of imaging, and treatment regimens received in such studies.

Health-related quality of life in high-grade glioma patients

Gliomas are malignant primary brain tumors and yet incurable. Palliation and the maintenance or improvement of the patient's quality of life is therefore of main importance. For that reason, health-related quality of life(HRQoL) has become an important outcome measure in clinical trials, next to traditional outcome measures such as overall and progression-free survivals, and radiological response to treatment. HRQoL is a multidimensional concept covering physical, psychological, and social domains, as well as symptoms induced by the disease and its treatment. HRQoL is assessed by using self-reported, validated questionnaires. Various generic HRQoL questionnaires, which can be supplemented with a brain tumor- specific module, are available. Both the tumor and its treatment can have a negative effect on HRQoL. However, treatment with surgery, radiotherapy, chemotherapy, and supportive treatment may also improve patients' HRQoL, in addition to extending survival. It is expected that the impact of HRQoL measurements in both clinical trials and clinical practice will increase. Hence, it is important that HRQoL data are collected, analyzed, and interpreted correctly. Methodological issues such as selection bias and missing data may hamper the interpretation of HRQoL data and should therefore be accounted. In clinical trials, HRQoL can be used to assess the benefits of a new treatment strategy, which should be weighed carefully against the adverse effects of that treatment. In daily clinical practice, HRQoL assessments of an individual patient can be used to inform physicians about the impact of a specific treatment strategy, and it may facilitate the communication between the physicians and the patients.

Conventional radiotherapy followed by IMRT as a boost in combination with chemotherapy treatment for high-grade gliomas:prognostic factors and outcomes

Objective： The aim of the study was to retrospectively evaluate the outcomes and important prognostic factors for patients with high-grade gliomas （HGG） treated with conventional radiotherapy （RT） followed by IMRT as a boost in combination with chemotherapy. Methods： From November 2004 to November 2006, 112 consecutive patients with high-grade gliomas were treated with radiotherapy, which included initial conventional radiotherapy and an IMRT boost to a total dose of 57.5-62.5 Gy, with 27-29 fractions delivered over 37-45 days. All cases received 3-6 cycles of chemotherapy, 63 cases received temozolomide, and another 49 cases received methyI-CCNU and teniposide. The acute and late treatment toxicities and the patterns of treatment failure were recorded. The overall survival （OS） rate and progression-free survival （PFS） rate were calculated, and the prognostic factors were analyzed. Results： Most of the acute radiation reactions were grade 1 or 2. No grade 4 acute reactions were noted. Three cases developed radiation necrosis. Grades Ⅰ, Ⅱ, and Ⅲ myelosuppressions were observed in 5, 32, and 12 cases of 49 patients treated with teniposide and methyl-CCNU, respectively. Grades Ⅰ and Ⅱ myelosuppressions were observed in 15 and 3 of the 63 patients who were treated with temozolomide, respectively. The 57 cases （50.9%） had recurred locally, and 13 cases （11.6%） had intracranial dissemination. The OS rates at 1, 2, and 3 years were 78.9%, 54.7%, and 30.8%, respectively. The PFS rates at 1,2, and 3 years were 63.8%, 38.9%, and 10.5%, respectively. A multivariate analysis showed that only tumor location and KPS were prognostic factors of OS. These same two variables and histopathology were statistically significant predictive factors in a multivariate analysis for PFS. Conclusion： Radiation toxicities were not found to be increased in this retrospective study with 112 consecutive patients of combined modality therapy including an IMRT boost treatment for HGG. Higher rate of local regional dissemination within the brain was observed than before. Tumor location, histopathology and KPS were important prognostic factors.

Drug clinical trials on high-grade gliomas: challenges and hopes

Gliomas are the most common group of malignant central nervous system tumors across all ages and have high heterogeneity.According to histopathologic criteria and molecular pathology,gliomas are classified as grades 1–4.High-grade gliomas(HGG),including the most aggressive subtype,glioblastoma(GBM),belong to grade 3 or 4.Although a standard therapy comprising surgical resection,chemotherapy,and radiation is available,almost all patients with HGG experience recurrence within several months and a dismal prognosis1.

A study on the relationship between long non-coding RNA H19 and high-grade glioma temozolomide resistance and their related mechanism

Objective:To investigate the expression level of long chain non coding RNAH19 in advanced gliomas and its relationship with glioma cell temozolomide (TMZ) resistance, and make a preliminary study on their related mechanism.Methods:Tissue samples of normal brain tissue, early onset and recurrence of high grade gliomas were collected, and the expression of LNC H19 was detected by reverse transcription polymerase chain reaction (RT-PCR). The construction of Resistant U251 TMZ Resistant (U251-TR) Cell Lines were completed by intermittent concentration gradient increments and verified by MTT method. The changes in the expression of LncRNA H19 was detected by RT-PCR, lovirus transfection was used to construct U251-TR cell line with stable interference with LNC H19 (U251-TRsiLNC H19), and MTT assay was used to observe the changes of TMZ half-maximal inhibitory concentration (IC50). Western Blot and RT-PCR were used to detect the changes of O6-methylguanine DNA methyltransferase (MGMT) in U251, U251-TR and U251-TRsiLNC H19.Results: The results of RT-PCR showed that the expression of LNC H19 in high-grade glioma was significantly higher than that in primary glioma tissue and normal brain tissue. The IC50 value and drug resistance index of U251-TR cell line were significantly increased, the expression of LncRNA H19 in U251-TR cell line was significantly higher than that in U251 cells and the expression of MGMT were also increased. We succeeded in interfering with the expression of LNC H19 in the U251-TR cell line, and found that the IC50 value and drug resistance index of U251-TR cell line were decreased significantly and the expression of MGMT were also decreased.Conclusion:LNC H19 is highly expressed in recurrent high-grade gliomas, which may increase the level of MGMT, leading to the occurrence of glioma cell TMZ resistance. LNC H19 is a key factor in the occurrence of TMZ resistance in glioma cells.

Role of pancreatic juice cytology in diagnosis of high-grade pancreatic intraepithelial neoplasia

High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.

Long-term adjuvant administration of temozolomide impacts serum ions concentration in high-grade glioma

Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentration is unclear.Methods:One hundred and thirty-eight patients with HGG were included.Their blood samples were collected for blood biochemistry and routine test.The alteration in serum ions concentration,total protein,albumin,globin,and blood cells counts were used to identify the impact of long-term TMZ chemotherapy.Results:Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles,we identified that serum potassium concentration had a downward trend after TMZ administration(1st vs.6th,p<0.001;1st vs.12th,p<0.001).Additionally,the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles(r=−0.649,p=0.023).The hematological adverse events mainly centered on grade 1 to 2.Conclusion:Long-term administration of TMZ may lead to serum ions disturbance.Besides the myelosuppression,we should pay attention to the alteration in serum ions concentration,and give patients proper symptomatic treatment when necessary.

Resection of high-grade glioma involving language areas assisted by multimodal techniques under general anesthesia:a retrospective study

Background Multimodal techniques-assisted resection of glioma under general anesthesia(GA)has been shown to achieve similar clinical outcomes as awake craniotomy(AC)in some studies.In this study,we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas(HGILAs)under GA.Methods HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center.Patients were separated into multimodal group(using neuronavigation,intraoperative MRI combined with direct electrical stimulation[DES]and neuromonitoring[IONM])and conventional group(neuronavigation alone)and clinical outcomes were compared between groups.Studies of HGILAs were reviewed systematically and the meta-analysis results of previous(GA or AC)studies were compared with our results.Results Finally,there were 263 patients in multimodal group and 137 patients in conventional group.Compared to the conventional group,the multimodal group achieved the higher median EOR(100%versus 94.32%,P<0.001)and rate of gross total resection(GTR)(73.8%versus 36.5%,P<0.001)and the lower incidence of permanent language deficit(PLD)(9.5%versus 19.7%,P=0.004).The multimodal group achieved the longer median PFS(16.8 versus 10.3 months,P<0.001)and OS(23.7 versus 15.7 months,P<0.001)than the conventional group.The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC(73.8%versus 55.7%[95%CI 32.0-79.3%]versus 53.4%[35.5-71.2%]).The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA(9.5%versus 14.0%[5.8-22.1%])and our incidence of PLD was a little higher than that of previous multimodal studies under AC(9.5%versus 7.5%[3.7-11.2%]).Our multimodal group also achieved a relative longer survival than previous studies.Conclusions Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA.Further prospective studies are needed to compare GA with AC for HGILAs.

High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

Bulk geochemistry,Rb-Sr,Sm-Nd,and stable O-H isotope systematics of the Metzimevin high-grade iron ore deposit,Mbalam iron ore district,southern Cameroon

Bulk geochemistry,Sr,Nd,and O-H isotope systematics are reported for the first time on banded iron formation(BIF)-hosted high-grade iron ore at the northwestern segment of Congo Craton(CC).Located in Mbalam iron ore district,Southern Cameroon,Metzimevin iron ore deposit is a hematite-magnetite BIF system,dominated by SiO_(2)+Fe_(2)O_(3)(97.1 to 99.84 wt%),with low concentrations of clastic elements e.g.,Al_(2)O_(3),TiO_(2),and HFSE,depicting a nearly pure chemical precipitate.The REE+Y signature of the iron deposit displays strong positive Eu anomaly,strong negative Ce anomaly,and chondritic to superchondritic Y/Ho ratios,suggestive of formation by mixed seawater-high temperature hydrothermal fluids in oxidising environment.The^(87)Sr/^(86)Sr ratios of the BIF are higher than the maximum^(87)Sr/^(86)Sr evolution curves for all Archean reservoirs(bulk silicate earth,Archean crust and Archean seawater),indicating involvement of continentally-derived components during BIF formation and alteration.TheƐ_(Nd)(t)(+2.26 to+3.77)and Nd model age indicate that chemical constituents for the BIF were derived from undifferentiated crustal source,between 3.002 and 2.88 Ga.The variable and diverse O and H isotope data(−1.9‰to 17.3‰and−57‰to 136‰respectively)indicate that the Metzimevin iron ore formed initially from magmatic plumes and later enriched by magmatic-metamorphic-modified meteoric fluids.Mass balance calculations indicate mineralisation by combined leaching and precipitation,with an average iron enrichment factor of>2.67 and SiO_(2)depletion factor of>0.99.This is associated with an overall volume reduction of 28.27%,reflecting net leaching and volume collapse of the BIF protholith.

Management of retroperitoneal high-grade serous carcinoma of unknown origin:A case report

BACKGROUND Retroperitoneal high-grade serous carcinoma(HGSC)of unknown origin is a sporadic tumor that can originate from ovarian cancer.Herein,we report the case of a woman with retroperitoneal HGSC of unknown origin and describe how she was diagnosed and treated.CASE SUMMARY A 71-year-old female presented with the tumor marker CA125 elevated to 1041.9 U/mL upon a regular health examination.Computed tomography revealed retroperitoneal lymph node enlargement.Subsequently,positron emission tomography scanning revealed lesions with increased F-18 fluorodeoxyglucose uptake at the nodes.As a result,she underwent laparoscopic lymph node resection,and pathology revealed metastatic adenocarcinoma with CK7(+),PAX8(+),WT1(+),PR(-),and p53 mutational loss of expression,indicating that the origin may be from the adnexa.The patient was admitted to our ward and underwent laparoscopic staging;however,the pathological results were negative.Under the suspicion of retroperitoneal HGSC of unknown origin,chemotherapy and targeted therapy were initiated.Tumor marker levels decreased after treatment.CONCLUSION We present a case of HGSC of unknown origin managed using retroperitoneal lymphadenectomy,staging surgery,chemotherapy,and targeted therapy.

Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps

BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.

High-grade serous carcinoma of the fallopian tube in a young woman with chromosomal 4q abnormality:A case report

BACKGROUND Few studies have reported an association between an increased risk of acquiring cancers and survival in patients with 4q deletion syndrome.This study presents a rare association between chromosome 4q abnormalities and fallopian tube highgrade serous carcinoma(HGSC)in a young woman.CASE SUMMARY A 35-year-old woman presented with acute dull abdominal pain and a known chromosomal abnormality involving 4q13.3 duplication and 4q23q24 deletion.Upon arrival at the emergency room,her abdomen appeared ovoid and distended with palpable shifting dullness.Ascites were identified through abdominal ultrasound,and computed tomography revealed an omentum cake and an enlarged bilateral adnexa.Blood tests showed elevated CA-125 levels.Paracentesis was conducted,and immunohistochemistry indicated that the cancer cells favored an ovarian origin,making us suspect ovarian cancer.The patient underwent debulking surgery,which led to a diagnosis of stage IIIC HGSC of the fallopian tube.Subsequently,the patient received adjuvant chemotherapy with carboplatin and paclitaxel,resulting in stable current condition.CONCLUSION This study demonstrates a rare correlation between a chromosome 4q abnormality and HGSC.UBE2D3 may affect crucial cancer-related pathways,including P53,BRCA,cyclin D,and tyrosine kinase receptors,thereby possibly contributing to cancer development.In addition,ADH1 and DDIT4 may be potential influencers of both carcinogenic and therapeutic responses.