scholarly journals H3K27me3 loss indicates an increased risk of recurrence in the Tübingen meningioma cohort

2020 ◽  
Author(s):  
Felix Behling ◽  
Christina Fodi ◽  
Irina Gepfner-Tuma ◽  
Kristina Kaltenbach ◽  
Mirjam Renovanz ◽  
...  

Abstract Background A loss of the trimethylation of lysine 27 of histone H3 (H3K27me3) in meningioma has been recently suggested as an adjunct to identify subsets of higher risk of recurrence. The aim of the present study was to assess the prognostic value of H3K27 histone trimethylation and its potential clinical utility in the “Tübingen meningioma cohort”. Methods Patients who underwent meningioma resection between 10/2003 and 1/22015 at the University Hospital Tübingen were included. Immunohistochemical stainings for H3K27me3 and the proliferation marker MIB1 were assessed and correlated with clinical parameters using univariate and multivariate cox regressions as well as Pearson’s chi-squared and log-rank test. Results Overall, 1268 meningiomas were analyzed with a female to male ratio of 2.6 and a mean age of 58.7 years (range 8.3 – 91.0). With 163 cases lost to follow up, 1103 cases were available for further analysis with a mean follow-up of 40.3 months (range 1.1 – 186.3). Male gender, younger age, intracranial tumor localization, progressive tumor, subtotal resection, higher WHO grade, increased MIB1 rate and loss of H3K27me3 were significant negative prognostic factors in the univariate analysis. H3K27me3 status and all other prognostic factors, except age and tumor location, remained significant in the multivariate model. Furthermore, adjuvant radiotherapy was an independent positive prognostic factor. Conclusions Loss of H3K27me3 combined with MIB1 labeling index are independent prognostic factors in meningioma. These data from the Tübingen meningioma cohort support the clinical utility of H3K27me3 immunohistochemical staining in meningioma and its integration into the routine histopathological workup.

2021 ◽  
Author(s):  
Muhammet Enes Gurses ◽  
Hatice Yagmur Zengin ◽  
Aysel Shıkhaliyeva ◽  
Cengiz Savas Askun ◽  
Melike Mut

Abstract Background Atypical meningiomas (AMs) constitute 18% of meningiomas. Predictors of recurrence are still indeterminate, and the timing of RT whether to treat with radiation upfront or at initial recurrence remains controversial, especially after gross total resection (GTR). Methods A retrospective study of AMs with uni-and multivariate analyses was conducted with clinical, surgical, radiological, and histopathological parameters. The prognostic factors associated with increased risk of recurrence were elucidated in the whole series and in the subgroup with GTR only. Results Subtotal resection (STR), skullbase-tentorium localization, no adjuvant RT, and progesterone-negativity caused tumor recurrence in 37 patients with a median follow-up of 48 (2-120) months. Among subgroup of 23 patients GTR only, 30.8% showed recurrence in a median of 39.65 months. AMs with a preoperative volume ≥27.5 cm3 disclosed a significantly higher risk of recurrence (a 9.3 fold increase) than those with <27.5 cm3 (66.7% vs. 14.3%, respectively). Skullbase-tentorium localization and progesterone negativity tend to have higher recurrence rates after GTR. Conclusions Preoperative volume was found to be a prognostic factor for AMs with a cut-off value of 27.5 cm3 for the first time in the literature. Our results disclosed that RT could be delayed with active monitorization after GTR for AMs, which are smaller than 27.5 cm3, not localized in skullbase-tentorium and progesterone-positive. Otherwise, early postop RT would be a safer approach without waiting the recurrence for AMs.


Author(s):  
Alan Siu ◽  
Sanjeet Rangarajan ◽  
Michael Karsy ◽  
Christopher J. Farrell ◽  
Gurston Nyquist ◽  
...  

Abstract Introduction Pituitary apoplexy is an uncommon clinical condition that can require urgent surgical intervention, but the factors resulting in recurrent apoplexy remain unclear. The purpose of this study is to determine the risks of a recurrent apoplexy and better understand the goals of surgical treatment. Methods A retrospective chart review was performed for all consecutive patients diagnosed and surgically treated for pituitary apoplexy from 2004 to 2021. Univariate analysis was performed to identify risk factors associated with recurrent apoplexy. Results A total of 115 patients were diagnosed with pituitary apoplexy with 11 patients showing recurrent apoplexy. This occurred at a rate of 2.2 cases per 100 patient-years of follow-up. There were no major differences in demographic factors, such as hypertension or anticoagulation use. There were no differences in tumor locations, cavernous sinus invasion, or tumor volumes (6.84 ± 4.61 vs. 9.15 ± 8.45 cm, p = 0.5). Patients with recurrent apoplexy were less likely to present with headache (27.3%) or ophthalmoplegia (9.1%). Recurrent apoplexy was associated with prior radiation (0.0 vs. 27.3%, p = 0.0001) and prior subtotal resection (10.6 vs. 90.9%, p = 0.0001) compared with first time apoplexy. The mean time to recurrent apoplexy was 48.3 ± 76.9 months and no differences in overall follow-up were seen in this group. Conclusion Recurrent pituitary apoplexy represents a rare event with limited understanding of pathophysiology. Prior STR and radiation treatment are associated with an increased risk. The relatively long time from the first apoplectic event to a recurrence suggests long-term patient follow-up is necessary.


Sarcoma ◽  
2000 ◽  
Vol 4 (4) ◽  
pp. 173-177 ◽  
Author(s):  
N. J. Espat ◽  
J. J. Lewis ◽  
J. M. Woodruff ◽  
C. Antonescu ◽  
J. Xia ◽  
...  

Purpose.Angiosarcoma is a rare tumor with endothelial cell differentiation that may arise in any anatomic location.The purpose of this report was to identify prognostic factors on outcome in a group of prospectively followed patients with confirmed angiosarcoma.Subjects.Adult patients (>16 years old) with angiosarcoma treated between July 1982 and February 1998 were identified from a prospective database.Methods.Pathologic confirmation of all cases was performed prior to inclusion in this analysis. Various prognostic factors were evaluated for disease-specific survival. Survival was determined by the Kaplan– Meier method. Statistical significance was evaluated by log-rank test for univariate analysis and Cox stepwise regression for multivariate analysis (p<0.05).Results.Fifty patients were identified; at the initial evaluation, this group included 32 patients with a primary tumor, three with local recurrence and 15 with metastatic disease. Tumor sites included 16 head and neck and skin of head, eight extremity, seven trunk, six breast, five pelvis, four viscera and four thoracic. Median follow-up among survivors was 71 months (range, 38–191 months).Two- and 5-year disease-specific survival was 50 and 30%, respectively, with a median of 24 months. The factor predictive of tumor-related mortality was presentation status (p=0.001; relative risk, 5). Two-year disease-specific survival for patients presenting with recurrent or metastatic disease was 13%, compared with 70% for those with primary disease.


Author(s):  
Uğur Önal ◽  
Özge Aydın Güçlü ◽  
Halis AKALIN ◽  
Nilüfer Aylin Acet Öztürk ◽  
Cihan Semet ◽  
...  

Background: Determination of the prognostic factors which affects the mortality and morbidity in COVID-19 patients, has an importance in terms of planning the treatment and follow-up strategy. Material and Method: Patients who had COVID-19 diagnosis via microbiologically and/or radiologically between March and October 2020 in a tertiary-care university hospital were recorded retrospectively. Only adult patients (≥18 years) with clinical spectrum of moderate, severe and critical illness were included in the study according to National Institutes of Health (NIH) guideline. A p value of less than 0.05 was considered significant. Ethical committee approval was given from the Uludag University with decision number 2020-22/11. Also, the permission from Republic of Turkey, Ministry of Health was given. Results: A total number of 257 patients were included in the study. 30-day mortality rate was recorded as 14.4%. In univariate analysis; age, chronic renal failure, malignancy, cerebrovascular disease, number of comorbidities >2, dyspnea, cough, NIH severe and critical illness, oxygen saturation, respiratory rate, systolic and diastolic blood pressure, qSOFA, GCS, MEWS, SOFA, CURB-65, CCI, CRP, procalcitonin, CK, D-dimer, lymphocyte and thrombocyte levels, neutrophile-to-lymphocyte ratio, AST, albumin, hemoglobin, CK-MB, fibrinogen, LDH and potassium levels were found as statistically significant (p<0.05). In logistic regression analysis one point increase of SOFA (p<0.001, OR:1.861, 95%CI:1.403-2.468) and CURB-65 scores (p=0.002, OR:2.484, 95%CI:1.401-4.406) were found as statistically significant for 30-day mortality. In mortal patients, there were significant difference between the baseline, day 3, 7 and 14 results of D-dimer (p=0.01), Ferritin (p=0.042), leucocyte (p=0.019) and neutrophile count (p=0.007). Conclusion: In our study, SOFA and CURB-65 scores on admission were associated with mortality and these score systems might be useful tools for the prognosis in COVID-19 patients.In addition to this, D-dimer, Ferritin, leucocyte and neutrophile counts were significantly increased during the follow up in patients with mortality.


2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Manraj S. Kang ◽  
Kamal Sahni ◽  
Piyush Kumar ◽  
Rajneesh Madhok ◽  
Ratna Saxena ◽  
...  

<bold>Introduction:</bold> Cervical cancer is most common cancer in the rural and second most common in urban areas of our country. It accounts for 16% of all cancers. There are various clinical, Paper Submission Datepathological and radiological factors which dictate the prognosis of these cancer cervix patients. The present study evaluates clinical, pathological and radiological prognostic factors in cancer cervix treated with concurrent chemoradiation. <bold>Material and Methods:</bold> A total of 32 patients seen between 2012 and 2014 patients planned concurrent chemoradiation were evaluated in terms of clinical (age, stage, Hb% and HPV Paper Publication Date infection), pathological (histopathology type and subtype, grade, mitotic index, lymph-July 2016 vascular invasion and necrosis) and radiological (parametrial extension, disease dimension, lymph node, hydronephrosis and vascularity of tumour) prognostic factors. After pre-DOI treatment evaluation patient was planned for 3 Dimentional-Conformal Radiotherapy (50Gy/25#/5 weeks) with concurrent chemotherapy (Cisplatin 35mg/m<sup>2</sup>) followed by 3 applications of Intracavitary radiotherapy (6Gy/fraction) with 6 months follow up. Response was accessed according to WHO response criteria and univariate analysis was done using chi-square test. <bold>Results:</bold> Clinical factors: Age – better disease free survival in older patients (p value=0.003), stage - Lower stage had better survival (for stage Ib-IIa vs stage IIb p value = 0.003 and for stage Ib vs. IIIb p value = 0.0005), Hb% - 57% patients with Hb <10g/dl had recurrence at end of 6 months (p value=0.00001), HPV – High recurrence with HPV presence. Pathological factors like high Mitotic Index had more residual disease (p=0.0009), grade - No statistical significance. Radiological factors- volume of disease - 35 % patients with volume of disease > 6 cm had disease at end of 6 months, hydronephrosis - 40 % patient with hydronephrosis had recurrence (p value = 0.0005) at end of 6 months follow up and vascularity of tumour showed statistically no difference. <bold>Conclusion:</bold> Hb <10%, HPV infection, Mitotic index (3-5/HPF), stage IIIB, pelvic nodes were concluded as the independent poor prognostic factors.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1605.1-1605
Author(s):  
A. Umeda ◽  
M. Sawada ◽  
N. Watanabe ◽  
M. Suzuki ◽  
T. Naganawa ◽  
...  

Background:Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive dermatomyositis (DM) is frequently associated with rapidly progressive interstitial pneumonia (RPIP), whose prognosis is assumed to be poor[1]. Although outcome of DM-RPIP has been reported to be improved by early immunosuppressive therapy, we still experience the cases with severe outcome. Only several reports mentioned the prognostic factors and they have not been fully elucidated.Objectives:To identify the predictors of prognosis in patients with anti-MDA5 Ab-positive DM associated with interstitial pneumonia (DM-IP).Methods:Anti-MDA5 Ab-positive DM-IP patients admitted to Fujita Health University Hospital between January 2010 and October 2019 were consecutively included and stratified into 2 groups, the survived and the deceased groups. DM was diagnosed according to the criteria proposed by Bohan and Peter[2]. Clinically amyopathic DM was diagnosed according to the criteria proposed by Sontheimer [3]. Diagnosis of IP was based on findings of high resolution CT scan (HRCT). The definition of RPIP was rapid exacerbation of hypoxemia or HRCT findings in a period of days to one month after the onset. Clinical features and prognosis of the patients were collected retrospectively and compared between groups. Candidates of predictors are extracted by the univariable analysis using Fisher’s exact test for dichotic parameters and Wilcoxon signed-rank test for continuous parameters and multivariable analysis using logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was examined to obtain the cut-off level. Survival was examined using Kaplan-Meier method and Log-rank test.Results:Twenty-one patients were involved. Eight were deceased and 13 were survived. The deceased group had a higher ratio of male (75% versus 25%, p= 0.018). All deceased cases were with RPIP and 67 % in the survived cases. Levels of serum ferritin (4490 versus 646 ng/mL, p = 0.0026), CRP (2.1 versus 0.9 mg/dL, p = 0.0490), CK (1150 versus 290 U/L, p = 0.017), AST (194 versus 108 U/L, p = 0.025) and LDH (674 versus 368 U/L, p = 0.011) were higher in the deceased group. Interestingly, skin ulcers were tended to be more frequent (12.5% versus 87.5%, p= 0.0587), and anti-SS-A antibody was also more frequently detected (14.3% versus 85.7%, p=0.0072) in the survived group. Using ROC analysis cut-off values were 963 ng/mL for serum ferritin level (sensitivity 100%, specificity 83%), 0.7 mg/dL for CRP (sensitivity 75%, specificity 69%), 308 U/L for CK (sensitivity 88%, specificity 77%), 62 U/L for ALT (sensitivity 100%, specificity 62%), and 454 U/L for LDH (sensitivity 88%, specificity 77%). Patients were divided into two groups based on these cut-offs or based on dichotic parameters and survival was examined between 2 groups. Except CRP and anti-SS-A antibody, survival was significantly worse in parameter-positive or higher groups. Interestingly, anti-SS-A antibody-positive group had better outcome compared with those without.Conclusion:In our analysis, novel candidates such as serum CK, AST, and LDH levels were newly extracted and parameters previously reported was also included and those were also associated with the clinical outcome. In addition, anti-SS-A antibody was identified as a novel protective factor associated with a good outcome.References:[1]Nakashima R, Hosono Y, Mimori T. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease. Lupus 2016;25:925-33.[2]Bohan A, Peter JB. Polymyositis and dermatomyositis. N Eng J Med 1975;292:344-7.[3]Sontheimer RD. Dermatomyositis: an overview of recent progress with emphasis on dermatologic aspects. Dermatol Clin 2000;20:387-408.Disclosure of Interests:None declared


2021 ◽  
Vol 108 (Supplement_3) ◽  
Author(s):  
G Martínez Izquierdo ◽  
A R Arnaiz Pérez ◽  
E Escolano Fernández ◽  
M Merayo Álvarez ◽  
B Carrasco Aguilera ◽  
...  

Abstract INTRODUCTION Renal cell carcinoma (RCC) represents 3% of overall malignant neoplasms in adults. However, its aetiology has not been clearly established. Although surgery represents the cornerstone in treatment, recurrence postoperative rates are around 20-30%, what implies prognostic factors search must be mandatory in order to help to plan de follow-up and the different adjuvant therapy possibilities available in case they were necessary. MATERIAL AND METHODS A retrospective observational study was carried out in 110 patients who underwent radical nephrectomy between 2004 and 2018, with the aim of identifying possible prognostic factors of recurrence of RCC after these surgeries. Preoperative data (epidemiological, comorbidities and laboratory tests), surgical, pathological and variables related to follow-up were taken into account. A univariate and multivariate analysis were performed, using chi-square test and logistic regression, respectively. RESULTS The median follow-up time was 53.5 months (SD = 35.8), time in which 19 patients had a recurrence of RCC after radical nephrectomy (17.2%). Histopathological items such as the surgical piece size, the nodal and microvascular invasion, the renal sinus invasion and the presence of necrosis in the surgical piece were associated with RCC recurrence in the univariate analysis, while only the presence of necrosis in the surgical piece showed a significant result in the multivariate analysis (p = 0.004). CONCLUSIONS Histopathological analysis, highlighting the presence of necrosis in the histological sample, was proved to be the main risk factor of RCC recurrence.


2021 ◽  
Author(s):  
Gema Ariceta ◽  
Fadi Fakhouri ◽  
Lisa Sartz ◽  
Benjamin Miller ◽  
Vasilis Nikolaou ◽  
...  

ABSTRACT Background Eculizumab modifies the course of disease in patients with atypical hemolytic uremic syndrome (aHUS), but data evaluating whether eculizumab discontinuation is safe are limited. Methods Patients enrolled in the Global aHUS Registry who received ≥1 month of eculizumab before discontinuing, demonstrated hematologic or renal response prior to discontinuation and had ≥6 months of follow-up were analyzed. The primary endpoint was the proportion of patients suffering thrombotic microangiopathy (TMA) recurrence after eculizumab discontinuation. Additional endpoints included: eGFR changes following eculizumab discontinuation to last available follow-up; number of TMA recurrences; time to TMA recurrence; proportion of patients restarting eculizumab; and changes in renal function. Results We analyzed 151 patients with clinically diagnosed aHUS who had evidence of hematologic or renal response to eculizumab, before discontinuing. Thirty-three (22%) experienced a TMA recurrence. Univariate analysis revealed that patients with an increased risk of TMA recurrence after discontinuing eculizumab were those with a history of extrarenal manifestations prior to initiating eculizumab, pathogenic variants, or a family history of aHUS. Multivariate analysis showed an increased risk of TMA recurrence in patients with pathogenic variants and a family history of aHUS. Twelve (8%) patients progressed to end-stage renal disease after eculizumab discontinuation; 7 (5%) patients eventually received a kidney transplant. Forty (27%) patients experienced an extrarenal manifestation of aHUS after eculizumab discontinuation. Conclusions Eculizumab discontinuation in patients with aHUS is not without risk, potentially leading to TMA recurrence and renal failure. A thorough assessment of risk factors prior to the decision to discontinue eculizumab is essential.


2018 ◽  
Vol 79 (S 04) ◽  
pp. S362-S370 ◽  
Author(s):  
Constantin Tuleasca ◽  
Alda Rocca ◽  
Mercy George ◽  
Etienne Pralong ◽  
Luis Schiappacasse ◽  
...  

Objective Planned subtotal resection followed by Gamma Knife surgery (GKS) in patients with large vestibular schwannoma (VS) has emerged during the past decade, with the aim of a better functional outcome for facial and cochlear function. Methods We prospectively collected patient data, surgical, and dosimetric parameters of a consecutive series of patients treated by this method at Lausanne University Hospital during the past 8 years. Results A consecutive series of 47 patients were treated between July 2010 and January 2018. The mean follow-up after surgery was 37.5 months (median: 36, range: 0.5–96). Mean presurgical tumor volume was 11.8 mL (1.47–34.9). Postoperative status showed normal facial nerve function (House–Brackmann I) in all patients. In a subgroup of 28 patients, with serviceable hearing before surgery and in which cochlear nerve preservation was attempted at surgery, 26 (92.8%) retained serviceable hearing. Nineteen had good or excellent hearing (Gardner–Robertson class 1) before surgery, and 16 (84.2%) retained it after surgery. Mean duration between surgery and GKS was 6 months (median: 5, range: 3–13.9). Mean residual volume as compared with the preoperative one at GKS was 31%. Mean marginal dose was 12 Gy (11–12). Mean follow-up after GKS was 34.4 months (6–84). Conclusion Our data show excellent results in large VS management with a combined approach of microsurgical subtotal resection and GKS on the residual tumor, with regard to the functional outcome and tumor control. Longer term follow-up is necessary to fully evaluate this approach, especially regarding tumor control.


Sign in / Sign up

Export Citation Format

Share Document