scholarly journals IDH mutation is paradoxically associated with higher 18F-FDOPA PET uptake in diffuse grade II and grade III gliomas

2017 ◽  
Vol 44 (8) ◽  
pp. 1306-1311 ◽  
Author(s):  
A. Verger ◽  
Ph. Metellus ◽  
Q. Sala ◽  
C. Colin ◽  
E. Bialecki ◽  
...  
Keyword(s):  
Grade Ii ◽  
2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii71-iii72
Author(s):  
M Diaz ◽  
J Jo ◽  
D Schiff

Abstract BACKGROUND VTE affects up to 30% of patients with glioblastoma (GBM, WHO grade IV), but little is known about its incidence in lower-grade gliomas (LGG, WHO grade II-III). It has been suggested that isocitrate dehydrogenase (IDH) mutation status dramatically decreases the incidence of VTE in glioma patients, through a combination of F3 promoter hypermethylation leading to lower expression of the procoagulant protein tissue factor, and an increased production of D-2-hydroxyglutarate, which has anticoagulant properties (Unruh et al, 2016). Our objective was to determine the incidence of VTE in LGG and stratify VTE risk by molecular subtype in gliomas grade II-IV. MATERIAL AND METHODS We performed a retrospective analysis of 590 glioma patients with molecular testing seen at our institution (UVa) from January 2005 to August 2017. We divided LGG patients into 3 groups: IDH-wildtype (IDHwt); IDH-mutant (IDHmt), 1p/19q-codeleted; and IDHmt, 1p/19q-intact. GBM patients were divided according to MGMT methylation status. Estimates of cumulative incidence of VTE were calculated with death as competing risk, and significance testing was determined using the Fine and Gray model. RESULTS Of 256 LGG patients (147 grade II and 109 grade III), 81 were IDHwt, 113 IDHmt and 1p/19q-codeleted, and 62 IDHmt and 1p/19q-intact. There were 334 GBM patients, with MGMT methylation status available in 263 (98 (37%) methylated and 165 (63%) unmethylated). With a median follow-up of 545 days, the overall incidence of VTE was 8.2% for grade II, 9.2% for grade III and 30.5% for grade IV. The 6-, 12- and 24-month VTE incidence was 4.1%, 4.8% and 5.4% respectively for grade II, 4.6%, 7.3% and 9.2% for grade III and 23.1%, 26.6% and 29% for grade IV. In LGG patients, VTE incidence was slightly higher in IDHwt tumors (11.1%) vs IDHmt, 1p/19q-codeleted (8.8%) and IDHmt, 1p/19q-intact tumors (4.8%). However, this difference was not statistically significant (IDHwt vs IDHmt, 1p/19q-codeleted, sub-distribution hazard ratio (SHR)=1.67, 95% CI=0.59–4.72; IDHwt vs IDHmt, 1p/19q-intact, SHR=1.87, 95% CI=0.54–6.53). In GBM patients, there was no difference in the VTE incidence according to MGMT methylation status (SHR=0.99, 95% CI=0.64–1.54). CONCLUSION In our cohort, the risk of VTE in GBM patients was consistent with historical data; patients with LGG also had a higher VTE risk compared to the general population. In contrast to other retrospective studies in which the incidence of VTE for grade II-IV IDHmt gliomas was 0% (Unruh et al, 2016; Nazari et al, 2018), our data suggest that VTEs do occur in IDHmt LGG patients, although at a lower rate than in IDHwt. MGMT methylation does not seem to influence the incidence of VTE. VTE risk stratification in GBM patients based on IDH mutation is forthcoming.


2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi17-vi18
Author(s):  
Eriel Sandika Pareira ◽  
Makoto Shibuya ◽  
Kentaro Ohara ◽  
Yu Nakagawa ◽  
Tokunori Kanazawa ◽  
...  

Abstract It is found that molecular characteristics in lower grade gliomas (LrGGs) such as codeletion of 1p/19q and IDH mutation was found to be more accurate to predict the patient`s clinical outcome compared to morphological diagnoses alone. Since the revision WHO2016 classification of LrGGs, molecular characteristics were implemented as diagnostic standard for LrGGs diagnoses. In the other hand, morphological diagnostic standard before WHO2016 classification era was determined by different considerations and therapeutic strategies. The malignancy grades were also majorly determined by morphological diagnoses only. This study re-evaluated 20 years of LrGG cases in single institution based on WHO2007 morphological criteria and compared them to the original institutional diagnoses from each era. The study samples were originally grade II-III diffuse glioma-diagnosed cases resected from 1990 to 2016. Biopsy cases were excluded. IDH mutation was analyzed by Sanger sequence and 1p/19 codeletion status was analyzed by Comparative Genome Hybridization (CGH). As the result 93 cases were collected and based on original diagnoses, more than 50% cases are astrocytomas. Compared to re-assessment by morphological diagnoses (WHO 2007), case numbers of astrocytoma diagnoses are decreased whereas oligodendroglioma and oligoastrocytoma case numbers are increased. But, based on WHO2016 criteria, the case number of astrocytomas is again found to be increased. From comparison between original institutional diagnoses and re-assessment results, it is found that there is a shift of trend from astrocytoma to oligodendroglioma and from grade II to grade III. Comparison between morphological diagnoses (WHO2007) and molecular (WHO2016) found that astrocytoma diagnoses remain unchanged meanwhile 45% of oligodendroglioma diagnoses were shifted into astrocytomas. There is a probability that there are high frequency of morphologically diagnosed oligodendroglioma tumors which are having molecular characteristics of astrocytoma. There is a trend that diagnosed grade II LrGGs are actually grade III based on re-assessment diagnosis.


Author(s):  
А.В. Бойко ◽  
Н.Д. Олтаржевская ◽  
В.И. Швец ◽  
Л.В. Демидова ◽  
Е.А. Дунаева ◽  
...  

Цель исследования. Разработка методов сопроводительной терапии для защиты нормальных органов и тканей, входящих в зону облучения. Методы. В исследование включено 112 больных раком шейки и тела матки после комбинированного или самостоятельного лучевого лечения с 2012 по 2016 гг. У 71 пациентки основной группы в качестве терапии сопровождения применяли гидрогель с деринатом и у 41 больной группы контроля - традиционные методы профилактики (масло оливковое, подсолнечное, метилурациловая мазь). Для профилактики эпителиита слизистой влагалища и шейки матки в основной группе использовали гидрогель в виде аппликаций с первого дня облучения. Для профилактики лучевого ректита гидрогель вводили в прямую кишку 1 раз в день с первого дня облучения. Инстилляции гидрогеля в мочевой пузырь начинали только при развитии первых признаков клинической картины цистита. Пациенткам контрольной группы для профилактики лучевых реакций проводились масляные, мазевые аппликации во влагалище, масляные микроклизмы в прямую кишку с первого дня облучения. Лечение лучевого цистита проводили с помощью растительных диуретиков, уросептиков. Результаты. Применение гидрогеля с деринатом позволило провести курс лучевой терапии без перерыва у 84,5% (60/71) больных, в контрольной группе - лишь у 48,8% (20/41). Лучевые циститы возникали в 2,5 раза реже (25,3% ± 3,3 против 63,4% ± 2,7, р<0,01). Анализ степени выраженности лучевого цистита по RTOG в двух группах показал, что у 75% больных основной группы наблюдалась I степень, у 25% - II степень, III и IV степени не отмечено, тогда как в контрольной группе лучевой цистит I степени развился у 44% пациенток, II - 40% и III - 16% больных. Применение гидрогеля снизило частоту лучевых ректитов в 2 раза (26,7% ± 3,3 против 53,7% ± 3,2 р<0,1).При использовании ежедневных аппликаций гидрогеля с деринатом со стороны слизистой оболочки влагалища и шейки матки преобладали эпителииты I степени (53,5%), II степень наблюдалась у 29,5% и III степень лучевой реакции - лишь в 16,9% случаев, IV степень реакции не отмечена. В контрольной группе эти показатели составили 26,8%, 24,3%, 31,7% и 17,2% соответственно. Разработаны цитологические критерии оценки течения лучевых реакций слизистой влагалища. Выделены три степени изменения цитограммы, которые коррелировали с клинической картиной. В основной группе лучевые изменения I степени зафиксированы в 4,5 раза чаще (52 ± 9,9% против 11,5 ± 6,3%, р<0,002), а III степень представлена в 3,8 раза реже, чем в контрольной группе (12 ± 6,5% против 46,1 ± 9,8%, р<0,003). Заключение. Применение гидрогелевого материала с деринатом в качестве препарата сопроводительной терапии во время курса облучения позволяет уменьшить частоту и степень выраженности лучевых повреждений со стороны слизистой влагалища, мочевого пузыря и прямой кишки, провести курс лучевой терапии без перерыва и улучшить качество жизни пациенток. Objective. Development of methods for accompanying therapy to protect normal organs and tissues in the irradiation zone. Method. The study included 112 patients with cervical and endometrial cancer after combined or independent radiotherapy from 2012 to 2016. In 71 female patients of the main group, Derinat with hydrogel was applied as a supportive therapy and in 41 patients of the control group, conventional prevention methods (olive oil, sunflower oil, methyluracyl ointment) were applied. For prevention of vaginal mucosal and cervical epitheliitis in the main group, hydrogel was used as applications from the first radiation day. For prevention of radiation proctitis, hydrogel was injected into the rectum once daily from the first radiation day. Hydrogel instillations into the bladder were started only with the first clinical signs of cystitis. For prevention of radiation reactions, vaginal oil and ointment and rectal oil micro-enema were administered to patients of the control group from the first day of irradiation. Radiation cystitis was treated with vegetable diuretics and uroseptic drugs. Results. Using the hydrogel with Derinat allowed to administer a course of radiotherapy without interruption in 84.5% (60/71) of patients and only in 48.8% (20/41) in the control group. Radiation cystitis occurred 60% less frequently (25.3% ± 3.3 versus 63.4% ± 2.7, p <0.01). Analysis of radiation cystitis severity in two groups (according to RTOG) showed that 75% of patients in the main group had grade I and 25% had grade II. Grade III and grade IV did not occur. At the same time, in the control group, grade I radiation cystitis developed in 44% of patients, grade II - in 40%, and grade III - in 16% of patients. The hydrogel treatment halved the frequency of radiation proctitis (26.7% ± 3.3 vs. 53.7% ± 3.2 p <0.1). With daily application of the hydrogel with Derinat, grade I epitheliitis (53.5%) predominated in vaginal and cervical mucosa, grade II was observed in 29.5%, and grade III radiation reaction - only in 16.9% of cases; grade IV reaction was not observed. In the control group, these proportions were 26.8%, 24.3%, 31.7%, and 17.2%, respectively. Cytological criteria were developed to evaluate the course of radiation reactions in the vaginal mucosa. Three degrees of change in the cytogram were identified, which correlated with clinical picture. In the main group, incidence of grade I radiation-induced changes was increased by more than 350% (52 ± 9.9% vs. 11.5 ± 6.3%, p <0.002), and incidence of grade III was decreased by more than 70% compared to the control group (12 ± 6.5% vs. 46.1 ± 9.8%, p <0.003). Conclusion. Using the hydrogel material with Derinat as an accompanying therapy during the course of irradiation allows to reduce frequency and severity of radiation injuries of the vaginal mucosa, bladder, and rectum, administer an uninterrupted course of radiotherapy, and improve the quality of life of patients.


2007 ◽  
Vol 107 (3) ◽  
pp. 600-609 ◽  
Author(s):  
Robert G. Whitmore ◽  
Jaroslaw Krejza ◽  
Gurpreet S. Kapoor ◽  
Jason Huse ◽  
John H. Woo ◽  
...  

Object Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms. Methods Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade. Results In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96–3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27–2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59–6.26; four patients) and Group 2 (mean 2.83, range 1.81–3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59–6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96–3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively. Conclusions Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.


Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 734
Author(s):  
Ivona Djordjevic ◽  
Dragoljub Zivanovic ◽  
Ivana Budic ◽  
Ana Kostic ◽  
Danijela Djeric

Background and objectives: For the last three decades, non-operative management (NOM) has been the standard in the treatment of clinically stable patients with blunt spleen injury, with a success rate of up to 95%. However, there are no prospective issues in the literature dealing with the incidence and type of splenic complications after NOM. Materials and methods: This study analyzed 76 pediatric patients, up to the age of 18, with blunt splenic injury who were treated non-operatively. All patients were included in a posttraumatic follow-up protocol with ultrasound examinations 4 and 12 weeks after injury. Results: The mean age of the children was 9.58 ± 3.97 years (range 1.98 to 17.75 years), with no statistically significant difference between the genders. The severity of the injury was determined according to the American Association for Surgery of Trauma (AAST) classification: 7 patients had grade I injuries (89.21%), 21 patients had grade II injuries (27.63%), 33 patients had grade III injuries (43.42%), and 15 patients had grade IV injuries (19.73%). The majority of the injuries were so-called high-energy ones, which were recorded in 45 patients (59.21%). According to a previously created posttraumatic follow-up protocol, complications were detected in 16 patients (21.05%). Hematomas had the highest incidence and were detected in 11 patients (14.47%), while pseudocysts were detected in 3 (3.94%), and a splenic abscess and pseudoaneurysm were detected in 1 patient (1.31%), respectively. The complications were in a direct correlation with injury grade: seven occurred in patients with grade IV injuries (9.21%), five occurred in children with grade III injuries (6.57%), three occurred in patients with grade II injuries (3.94%), and one occurred in a patient with a grade I injury (1.31%). Conclusion: Based on the severity of the spleen injury, it is difficult to predict the further course of developing complications, but complications are more common in high-grade injuries. The implementation of a follow-up ultrasound protocol is mandatory in all patients with NOM of spleen injuries for the early detection of potentially dangerous and fatal complications.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii159-ii160
Author(s):  
Roberta Rudà ◽  
Riccardo Pascuzzo ◽  
Francesca Mo ◽  
Alessia Pellerino ◽  
Peter B Barker ◽  
...  

Abstract BACKGROUND There is lack of information on the role of excitatory and inhibitory neurotransmitters in the development of seizures in patients with lower grade gliomas. Increase of glutamate and downregulation of GABA have been suggested in preclinical models and human surgical samples to be associated with brain tumor-related epilepsy. MATERIAL AND METHODS We prospectively investigated with the use of magnetic resonance spectroscopy (MRS) the differences in the ratio of metabolites (glutamate/GABA, glutamate/creatine and GABA/creatine) in the peritumoral areas between patients with or without seizures in a series of lower grade gliomas. Tumors were classified according to WHO Classification of 2016 as follows:11 grade II IDH mutated and 1p/19q codeleted; 3 grade III IDH mutated and 1p/19q codeleted; 6 grade II IDH mutated and 1p/19q intact; 1 grade III IDH mutated and 1p/19q intact; 1 grade II IDH wild-type. Patients received surgery alone or followed by temozolomide chemotherapy according to the presence of risk factors. RESULTS At baseline evaluation, maximum glutamate/GABA values were significantly higher (p=0.023) in the peritumoral area of patients with seizures (1.008 ± 0.368) with respect to those without seizures (0.691 ± 0.170). No other metabolites ratio showed significant differences between the two groups. Similar results were obtained when analyzing the metabolites ratio in the examinations during the follow-up. In the cohort of patients with seizures (n.14) variations of metabolite ratios were not associated with tumor location, 1p/19q codeletion, use of AEDs, concomitant chemotherapy or seizure characteristics (type, duration, frequency). CONCLUSIONS The study is ongoing with the aim of analyzing further the correlations between ratio of metabolites and status of the tumor (stable vs progressive).


2015 ◽  
Vol 2015 ◽  
pp. 1-4
Author(s):  
Prerana N. Shah ◽  
Kaveri Das

Background. Video laryngoscopes provide better view and can improve ease of intubation compared with standard laryngoscopes. Methods. A prospective randomized study was done on 60 patients, 18 to 65 years old, comparing McGrath video laryngoscope and Macintosh laryngoscope. The aim was to compare the ease, efficacy, and usability of them during routine airway management. The primary endpoint was duration of intubation and the secondary endpoints were Cormack and Lehane grade of laryngoscopic view, number of intubation attempts, and incidence of complications. Results. There was an increase in total duration of intubation with McGrath video laryngoscope with 42.9 ± 19.5 seconds compared to Macintosh laryngoscope with 17.9 ± 4.6 seconds. In Macintosh group, 73.3% had grade I, 20% had grade II, and 6.7% had grade III Cormack Lehane view, while in McGrath group, 83.3% had grade I, 13.3% had grade II, and 3.3% had grade III. In McGrath group, 6 patients (20%) required more than 120 seconds to get intubated and only 73.3% were intubated in 1 attempt, while patients in Macintosh group had 100% successful intubation in 1 attempt. Pharyngeal trauma was seen with McGrath videolaryngoscopy. Conclusion. Duration of laryngoscopy, intubation, and total duration of intubation were significantly higher in McGrath group than in Macintosh group. McGrath group required a higher number of intubation attempts.


2012 ◽  
Vol 49 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Sthela Maria Murad-Regadas ◽  
Francisco Sergio P. Regadas ◽  
Lusmar Veras Rodrigues ◽  
Graziela Olivia da Silva Fernandes ◽  
Guilherme Buchen ◽  
...  

CONTEXT: Management of patients with obstructed defecation syndrome is still controversial. OBJECTIVE: To analyze the efficacy of clinical, clinical treatment followed by biofeedback, and surgical treatment in patients with obstructed defecation, rectocele and multiple dysfunctions evaluated with echodefecography. METHODS: The study included 103 females aged 26-84 years with obstructed defecation, grade-II/III rectocele and multiple dysfunctions on echodefecography. Patients were distributed into three treatment groups and constipation scores were assigned. Group I: 34 (33%) patients with significant improvement of symptoms through clinical management only. Group II: 14 (14%) with improvement through clinical treatment plus biofeedback. Group III: 55 (53%) referred to surgery due to treatment failure. RESULTS: Group I: 20 (59%) patients had grade-II rectocele, 14 (41%) grade-III. Obstructed defecation syndrome was associated with intussusception (41%), mucosal prolapse (41%), anismus (29%), enterocele (9%) or 2 dysfunctions (23%). The average constipation score decreased significantly from 11 to 5. Group II: 11 (79%) grade-II rectocele, 3 (21%) grade-III, associated with intussusception (7%), mucosal prolapse (43%), anismus (71%) or 2 dysfunctions (29%). There was significant decrease in constipation score from 13 to 6. Group III: 8 (15%) grade-II rectocele, 47 (85%) grade-III, associated with intussusception (42%), mucosal prolapse (40%) or 2 dysfunctions (32%). The constipation score remained unchanged despite clinical treatment and biofeedback. Twenty-three underwent surgery had a significantly decrease in constipation score from 12 to 4. The remaining 32 (31%) patients which 22 refused surgery, 6 had low anal pressure and 4 had slow transit. CONCLUSIONS: Approximately 50% of patients with obstructed defecation, rectocele and multiple dysfunctions presented a satisfactory response to clinical treatment and/or biofeedback. Surgical repair was mainly required in patients with grade-III rectocele whose constipation scores remained high despite all efforts.


2017 ◽  
Vol 20 (2) ◽  
pp. 183-190 ◽  
Author(s):  
Nickalus R. Khan ◽  
Brittany D. Fraser ◽  
Vincent Nguyen ◽  
Kenneth Moore ◽  
Scott Boop ◽  
...  

OBJECTIVEDespite established risk factors, abusive head trauma (AHT) continues to plague our communities. Cerebrovascular accident (CVA), depicted as areas of hypodensity on CT scans or diffusion restriction on MR images, is a well-known consequence of AHT, but its etiology remains elusive. The authors hypothesize that a CVA, in isolation or in conjunction with other intracranial injuries, compounds the severity of a child’s injury, which in turn leads to greater health care utilization, including surgical services, and an increased risk of death.METHODSThe authors conducted a retrospective observational study to evaluate data obtained in all children with AHT who presented to Le Bonheur Children’s Hospital (LBCH) from January 2009 through August 2016. Demographic, hospital course, radiological, cost, and readmission information was collected. Children with one or more CVA were compared with those without a CVA.RESULTSThe authors identified 282 children with AHT, of whom 79 (28%) had one or more CVA. Compared with individuals without a CVA, children with a stroke were of similar overall age (6 months), sex (61% male), and race (56% African-American) and had similar insurance status (81% public). Just under half of all children with a stroke (38/79, 48%) were between 1–6 months of age. Thirty-five stroke patients (44%) had a Grade II injury, and 44 (56%) had a Grade III injury. The majority of stroke cases were bilateral (78%), multifocal (85%), associated with an overlying subdural hematoma (86%), and were watershed/hypoperfusion in morphology (73%). Thirty-six children (46%) had a hemispheric stroke. There were a total of 48 neurosurgical procedures performed on 28 stroke patients. Overall median hospital length of stay (11 vs 3 days), total hospital charges ($13.8 vs $6.6 million), and mean charges per patient ($174,700 vs $32,500) were significantly higher in the stroke cohort as a whole, as well as by injury grade (II and III). Twenty children in the stroke cohort (25%) died as a direct result of their AHT, whereas only 2 children in the nonstroke cohort died (1%). There was a 30% readmission rate within the first 180-day postinjury period for patients in the stroke cohort, and of these, approximately 50% required additional neurosurgical intervention(s).CONCLUSIONSOne or more strokes in a child with AHT indicate a particularly severe injury. These children have longer hospital stays, greater hospital charges, and a greater likelihood of needing a neurosurgical intervention (i.e., bedside procedure or surgery). Stroke is such an important predictor of health care utilization and outcome that it warrants a subcategory for both Grade II and Grade III injuries. It should be noted that the word “stroke” or “CVA” should not automatically imply arterial compromise in this population.


1995 ◽  
Vol 36 (2) ◽  
pp. 163-167 ◽  
Author(s):  
H. Honda ◽  
H. Onitsuka ◽  
Y. Kanazawa ◽  
T. Matsumata ◽  
T. Hayashi ◽  
...  

In order to clarify the factors contributing to the signal intensities (SIs) of HCC on T1-weighted images, the amount of water, lipid, copper (Cu), iron (Fe), and manganese (Mn) was determined in HCC and surrounding hepatic parenchyma of 13 patients. The relationships among these findings, the histopathologic findings, and the SIs of T1-weighted images were evaluated. Among the 13 HCC, 3 had a high SI, 5 were isointense, and 5 had a low SI on T1-weighted images compared to the surrounding hepatic parenchyma. The paramagnetic ions which contributed to the SI patterns were assumed to be Cu in HCC (38.0±62.4 μg/g ww), and Fe in the liver (61.1±42.4 μg/g ww) and HCC (40.0±34.3 μg/g ww). In 8 HCC with high- or isointensity, 2 were grades I, 5 were grade II, and one was grade III according to the Edmondson-Steiner's histopathologic classification. It is concluded that the SI patterns alone can not be a sign of low grade malignancy because of the existence of Fe in livers and HCC.


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