scholarly journals CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer

2013 ◽  
Vol 2 (4) ◽  
pp. 186-195 ◽  
Author(s):  
Filomena Cetani ◽  
Chiara Banti ◽  
Elena Pardi ◽  
Simona Borsari ◽  
Paolo Viacava ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Survival Rates ◽  
Suppressor Gene ◽  
Added Value ◽  
Carrier Status ◽  
Mutational Status ◽  
Immunohistochemical Studies ◽  
Better Than

Inactivating mutations of the CDC73 tumor suppressor gene have been reported in parathyroid carcinomas (PC), in association with the loss of nuclear expression of the encoded protein, parafibromin. The aim of this study was to further investigate the role of the CDC73 gene in PC and evaluate whether gene carrier status and/or the loss of parafibromin staining might have an effect on the outcome of the disease. We performed genetic and immunohistochemical studies in parathyroid tumor samples from 35 patients with sporadic PC. Nonsense or frameshift CDC73 mutations were detected in 13 samples suitable for DNA sequencing. Six of these mutations were germline. Loss of parafibromin expression was found in 17 samples. The presence of the CDC73 mutation as well as the loss of parafibromin predicted a high likelihood of subsequent recurrence and/or metastasis (92.3%, P=0.049 and 94.1%, P=0.0017 respectively), but only the latter was associated with a decreased overall 5- and 10-year survival rates (59%, P=0.107, and 23%, P=0.0026 respectively). The presence of both the CDC73 mutation and loss of parafibromin staining compared with their absence predicted a lower overall survival at 10- (18 vs 84%, P=0.016) but not at 5-year follow-up. In conclusion, loss of parafibromin staining, better than CDC73 mutation, predicts the clinical outcome and mortality rate. The added value of CDC73 mutational analysis is the possibility of identifying germline mutations, which will prompt the screening of other family members.

scholarly journals Tipranavir (TPV) Genotypic Inhibitory Quotient Predicts Virological Response at 48 Weeks to TPV-Based Salvage Regimens

2007 ◽  
Vol 52 (3) ◽  
pp. 1066-1071 ◽  
Author(s):  
Daniel Gonzalez de Requena ◽  
Stefano Bonora ◽  
Andrea Calcagno ◽  
Antonio D'Avolio ◽  
Marco Siccardi ◽  
...  
Keyword(s):  
Virological Response ◽  
Protease Gene ◽  
Reverse Transcriptase Inhibitors ◽  
Cutoff Value ◽  
Multiple Drugs ◽  
The Relationship ◽  
Cell Count Increase ◽  
Better Than

ABSTRACT The virological response (VR) to a tipranavir-ritonavir (TPV-RTV)-based regimen had been shown to be associated with a number of mutations in the protease gene, the use of enfuvirtide (T20), and the TPV phenotypic inhibitory quotient (IQ). The role of the TPV genotypic IQ (gIQ) has not yet been fully investigated. The aim of our study was to evaluate the relationship between the TPV gIQ and the VR at 48 weeks to TPV-based salvage regimens. Patients placed on regimens containing two nucleoside reverse transcriptase inhibitors plus TPV-RTV 500/200 mg twice a day with or without T20 were prospectively studied. Regular follow-up was performed over the study period. VR, considered a viral load (VL) decrease of ≥1 log unit and/or the achievement of <50 copies/ml with no VL rebound of >0.5 log unit compared to the maximal VL decrease at week 48, was assessed. Thirty-eight patients who had received multiple drugs were included. At week 48 the VL decrease was −1.48 (interquartile range [IQR], −2.88 to −0.48), 15 patients (39.5%) had VLs of <50 copies/ml, and the CD4+ cell count increase was 37 cells/mm3 (IQR, −30 to +175). Twenty subjects (52.6%) achieved VRs. The TPV gIQ and optimized background score (OBS) were independently associated with higher VL decreases. The TPV gIQ and OBS were also independent predictors of a VR at week 48. TPV gIQ and OBS cutoff values of 14,500 and 2, respectively, were associated with a higher rate of VR. The TPV gIQ was shown to be able to predict the VR at 48 weeks to TPV-containing salvage regimens better than the TPV trough concentration or TPV-associated mutations alone. A possible TPV gIQ cutoff value of 14,500 for reaching a VR at week 48 was suggested. Further studies are needed in order to evaluate the calculation of TPV gIQ as a new tool for the optimization of TPV-based salvage therapy.

Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor (GIST) patients (pts) treated with imatinib mesylate

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9528-9528 ◽  
Author(s):  
C. D. Blanke ◽  
G. D. Demetri ◽  
M. Von Mehren ◽  
M. C. Heinrich ◽  
B. L. Eisenberg ◽  
...  
Keyword(s):  
Phase Ii ◽  
Survival Rates ◽  
Complete Response ◽  
Tumor Control ◽  
Term Survival ◽  
Mutational Status ◽  
Exon 9 ◽  
Exon 11

9528 Background: Imatinib achieves tumor control in most pts with advanced GIST, but the durability of remissions has not been well described. We now present an updated long-term analysis of a randomized phase II trial first presented in 2001, with a median follow-up of 52 months. Methods: 147 pts with unresectable or metastatic malignant GIST were randomized to treatment with daily dosing of imatinib, 400 or 600 mg po. Results: Two pts (1%) achieved a complete response, 98 (67%) achieved a partial response (PR), and 23 (16%) exhibited stable disease (SD) as their best response. Median time-to-response was 13 weeks (95% CI; 12–23 weeks), but one quarter of pts responded after 23 weeks. No significant response differences were seen between the two dose levels tested. The median duration of response was 27 months, and median overall survival was 58 months. Pts with SD or PR had similar 4-year survival rates (64% versus 62%). KIT and/or PDGFRA mutational analyses were obtained in 87% of patients, and the mutational status was highly significant in predicting outcome. GISTs harboring KIT mutations in exon 11, exon 9, and with no detectable mutations in KIT or PDGFRA demonstrated PR rates of 87%, 48%, and 0%, respectively. The median survival for pts with exon 11 KIT mutations has not yet been reached, and it was 45 months for those with exon 9 mutations. Conclusions: While late progression can be seen in GIST pts treated with imatinib, the majority of pts derive benefit. Survival in those achieving SD parallels those with PRs. Late responses are often seen in pts with initial SD, and responses in general are of lasting duration. In particular, pts with KIT mutations in exon 11 (the most common exon affected) have very high response rates and favorable long term survival. [Table: see text]

Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: A 10-year follow-up study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10058-10058
Author(s):  
Nicole Jannelle Look Hong ◽  
Francis J Hornicek ◽  
David C. Harmon ◽  
Edwin Choy ◽  
Yen-Lin Chen ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Rates ◽  
Neoadjuvant Chemoradiotherapy ◽  
Soft Tissue Sarcomas ◽  
Clinicopathologic Characteristics ◽  
Free Survival ◽  
Median Tumor Size ◽  
Recent Cohort ◽  
Better Than

10058 Background: Patients with high-risk extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of preoperative mesna, doxorubucin hydrochloride (Adriamycin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this series is to study outcomes of our most recent cohort of patients treated on this regimen. Methods: We retrospectively reviewed records of 55 consecutive patients with STS of the extremity or superficial trunk who completed all phases of treatment at our institution from January 2000–July 2011. Clinicopathologic characteristics and patient outcomes were analyzed. Results: Fifty-five patients were analyzed and had a median age of 53 years (range 18-73). The median tumor size was 10.1cm (range 2.5-35.5 cm). Twenty-seven (49%) and 28 (51%) patients had grade 2 and 3 tumors, respectively. Margins were negative in 49 (89%) patients, and positive in 6 (11%) patients. At a median follow-up of 43 months, there were 7 (13%) locoregional, and 17 (31%) distant recurrences. The local and distant 5-year recurrence-free survival (RFS) rates were 92% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. There were no significant predictors of OS or RFS. Conclusions: Outcomes of a contemporary cohort of patients with extremity and truncal STS treated with an intense regimen of neoadjuvant chemoradiotherapy and surgery are consistent with previous reports from our institution and better than reports of chemotherapy alone. [Table: see text]

Sarcoligo: Impact of local ablative treatment of oligometastatic sarcomas on overall survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10042-10042
Author(s):  
Juliette Thariat ◽  
Laurence Moureau-Zabotto ◽  
Nicolas Penel ◽  
Antoine Italiano ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Metastases ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Locoregional Treatment ◽  
Metastatic Sites ◽  
The Impact

10042 Background: 40-50% of sarcomas become metastatic. Median survival of metastatic patients has improved over time. The probably multifactorial reasons for such improvement are not fully clear. Noteworthy, for patients with a controlled primary and a limited number of lung metastases, complete resection of their metastases yields survival rates of up to 40% at three years. Advances in surgery, radiotherapy and radiofrequency have fostered the use of local treatments for various metastatic sites (lung, liver, spine...). Methods: A multicentric retrospective study of the Groupe Sarcome Francais (GSF-GETO); approved by the nationally-review board and ethical committee, was conducted to assess the impact of local ablative treatment on overall survival. Patients who had had oligometastases (any site, 1-5 synchronous metastases) at diagnostic or during the course of disease between 2000 and 2010 were included. Results: Median age of the 243 oligometastatic sarcoma patients was 53 years-old (11-86). Patients had grade I, II and III in 7.5%, 29.6% and 63.3% of cases, respectively with various histologies. 69% of patients underwent local ablative treatment of metastases. Median follow-up was 59 months (4-212) for living patients. Median overall survival was 51 months (1-348). On univariate analysis, grade, histology, absence of chemotherapy, local ablative treatment (surgery, irradiation, radiofrequency or chemoembolisation) correlated with survival but not age or site of oligometastasis. On multivariate analyses, grade (hazard ratio HR 0.12 [CI95 0.3-0.6]) and local ablative treatment (HR 3.8 [CI95 2.1-7.1]) remained significant. Conclusions: Local ablative treatment of metastases is associated with better survival in sarcoma patients with oligometastatic disease. The role of the locoregional treatment of metastases and its impact on quality of life should be assessed prospectively.

Exosomes as novel prognostic biomarker in potentially resectable colorectal cancer liver metastatic (CCLM) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3558-3558
Author(s):  
Ina Valeria Zurlo ◽  
Mariantonietta Di Salvatore ◽  
Donatella Lucchetti ◽  
Filomena Colella ◽  
Claudio Ricciardi Tenore ◽  
...  
Keyword(s):  
Liver Surgery ◽  
Scoring Systems ◽  
Aggressive Approach ◽  
Post Surgery ◽  
Mutational Status ◽  
Kras Status ◽  
The One ◽  
Major Hepatectomies

3558 Background: Target therapies and new surgical strategies deeply modify the history of CCLM patients (pts). Several prognostic scoring systems have been developed but no one is able to identify pts who should be excluded from a potentially useless surgery. Currently research is committed in identifying early biomarkers able to discern pts who could benefit from an aggressive approach. Exosomes are arising as promising biomarkers in cancer. The aim of this pivotal study was to analyze the association among exosome levels during CCLM-pts treatment, clinical outcomes and the KRAS status. Methods: We enrolled 22 pts with CCLM candidate to preoperative chemotherapy (pCT) and subsequent liver surgery. A blood sample was collected before pCT, after surgery, monthly during follow-up and at progression (PD). Exosomes were isolated by ultracentrifugation and characterized by standard methods. Exosomes concentration was assessed by Bradford assay. We adopted ddPCR™ KRAS G12/G13 Screening Kit to evaluate the KRAS status in exosomal DNA (e-DNA). Results: 22 CCLM pts received pCT and underwent liver surgery: 5 major hepatectomies and 17 multiple liver resections. Changes in exosomes plasma levels were found to correlate with each treatment step,resulting reduced after pCT and surgery and increased at PD, respectively (p = 0.0026). Pts with higher baseline exosome levels experimented shorter PFS than those with lower levels (p = 0.0033 HR 0.2). No association was found between exosome levels after liver surgery and disease free interval nor overall survival. KRAS status on e-DNA was evaluated on 10 pts in baseline, in pCT, after surgery, and in PD samples. In 8 out of 10 pts e-DNA displayed the same mutational status than the one detected on tumor DNA. Changes in e-DNA KRAS copies were found statistically significant in pCT vs surgery and pCT vs PD (p = 0.039; p = 0.04). Conclusions: Our study suggests a prognostic role of exosome levels in CCLM pts. Moreover, we showed that KRAS mutational status could be monitored during the post-surgery follow up by analyzing e-DNA. Overall, our data confirm the potential role of exosomes in liquid biopsy tool to monitor molecular changes during the treatment of CCLM pts.

Extracapillary Proliferative Glomerulonephritis in Children

PEDIATRICS ◽  
1975 ◽  
Vol 56 (3) ◽  
pp. 434-442
Author(s):  
Sudhir K. Anand ◽  
Carl W. Trygstad ◽  
Hari M. Sharma ◽  
James D. Northway
Keyword(s):  
Streptococcal Infection ◽  
Clinical Course ◽  
Renal Involvement ◽  
Therapeutic Agents ◽  
Proliferative Glomerulonephritis ◽  
The Mean ◽  
Histopathologic Changes ◽  
Better Than

The clinical course and renal pathology of 17 children with acute extracapillary proliferative glomerulonephritis is reported. Patients with systemic ses associated with renal involvement were excluded. The onset followed streptococcal infection in ten; of these, four have died, one has been transplanted, and the remaining five have completely healed. The mean follow-up of the latter five patients was 32 months (range, 18 to 57 months). Of the other seven patients without evidence of preceding streptococcal infection, two have died, two have been transplanted, and the remaining three all have hypertension, proteinuria, and reduced creatinine clearance. The mean follow-up of the latter three patients was 29 months (range, 14 to 38 months). The initial renal histopathologic changes and their progress in later renal biopsies is described. The role of various therapeutic agents is discussed. The prognosis in acute extracapillary proliferative glomerulonephritis following streptococcal infection appears to be better than in ones without preceding streptococcal infection.

Stereotactic Ablative Radiotherapy for Patients with Unresectable or Medically Inoperable Cholangiocarcinoma

2017 ◽  
Vol 103 (3) ◽  
pp. 236-241 ◽  
Author(s):  
Ming-Yueh Liu ◽  
Cheng-Hsiang Lo ◽  
Chun-Shu Lin ◽  
Hsing-Lung Chao ◽  
Jen-Fu Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Survival Duration ◽  
Stereotactic Ablative Radiotherapy ◽  
Radiation Induced ◽  
Effective Doses ◽  
Bile Duct Tumors ◽  
Overall Survival Rates

Purpose The role of stereotactic ablative radiotherapy (SABR) in patients with unresectable or medically inoperable cholangiocarcinoma remains unclear. We examined the efficacy and safety of SABR in this group of patients. Methods From January 2008 to December 2014, 15 patients with 17 lesions were included in this study. The lesions included 14 intrahepatic, 1 hilar, and 2 distal bile duct tumors. Three patients were classified as medically inoperable because of old age or multiple comorbidities. Tumors measured 0.8-13 cm (median, 3.6 cm). The median prescribed dose was 45 Gy delivered in 5 fractions over 5 consecutive days. Results The median follow-up period for surviving patients was 29.9 months. Objective responses were observed for 10 of 17 tumors (58.8%), including 3 complete responses (17.6%). The median survival duration was 12.6 months, and the 1- and 2-year overall survival rates were 50.3% and 14.4%, respectively. The 1- and 2-year in-field failure-free rates were 61.5% and 30.8%, respectively. For patients with biologically effective doses (BEDs) exceeding 75 Gy10, the 1- and 2-year overall survival rates were 58.3% and 33.3%, respectively, compared to 20.0% and 0%, respectively for those with BEDs lower than 75 Gy10. Radiation-induced liver disease did not develop in any patient. Acute toxicities were generally mild and tolerable. Conclusions Stereotactic ablative radiotherapy could be an alternative treatment for unresectable or medically inoperable cholangiocarcinoma. Further dose escalation may be considered to optimize local control.

scholarly journals An Amino Acids Mixture Improves the Hepatotoxicity Induced by Acetaminophen in Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Francesco Di Pierro ◽  
Giuseppe Rossoni
Keyword(s):  
Survival Rates ◽  
Weight Ratio ◽  
Liver Weight ◽  
Protective Role ◽  
High Dose ◽  
Dependent Manner ◽  
Total Glutathione ◽  
Dose Dependent ◽  
Better Than

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but at high dose it leads to undesirable side effects, such as hepatotoxicity and nephrotoxicity. The aim of this study was to evaluate the protective role of DDM-GSH, a mixture of L-cysteine, L-methionine, and L-serine in a weight ratio of 2 : 1 : 1, in comparison to N-acetylcysteine (NAC), against acetaminophen- (APAP-) induced hepatotoxicity in mice. Toxicity was induced in mice by the intraperitoneal (ip) administration of low dose (2 mmol/kg) or high dose (8 mmol/kg) of APAP. DDM-GSH (0.4 to 1.6 mmol/kg) was given ip to mice 1 h before the APAP administration. The same was done with NAC (0.9 to 3.6 mmol/kg), the standard antidote of APAP toxicity. Mice were sacrificed 8 h after the APAP injection to determine liver weight, serum alanine aminotransferase (ALT), and total glutathione (GSH) depletion and malondialdehyde (MDA) accumulation in liver tissues. DDM-GSH improved mouse survival rates better than NAC against a high dose of APAP. Moreover, DDM-GSH significantly reduced in a dose-dependent manner not only APAP-induced increases of ALT but also APAP-induced hepatic GSH depletion and MDA accumulation. Our results suggest that DDM-GSH may be more potent than NAC in protecting the liver from APAP-induced liver injury.

Selective placement of autogenous arteriovenous fistulae in an over 80-year-old population

2018 ◽  
Vol 19 (1) ◽  
pp. 40-44 ◽  
Author(s):  
Keagan Werner-Gibbings ◽  
Liesl Ischia ◽  
William Butcher ◽  
Richard Ward-Harvey ◽  
Jonathan Stewart ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Demographic Data ◽  
Survival Rates ◽  
Primary Patency ◽  
University Hospital ◽  
Selective Placement ◽  
Minimal Evidence ◽  
Better Than

Introduction: With improved life expectancy and quality of life, elderly patients constitute a progressively larger fraction of consumers utilising renal replacement therapy (RRT). Although substantial data exist for younger cohorts, minimal evidence exists for outcomes of arteriovenous fistula (AVF) and central catheters (CVC) placed in those patients over 80 years. We examined outcomes of primary AVF placement in this cohort to ascertain durability and benefits of AVF in the over 80-year-old population. Methods: Retrospective analysis was undertaken of all autogenous AVFs and CVCs placed in patients aged over 80 years at Gold Coast University Hospital between March 2010 and February 2016. Prospectively collected demographic data, co-morbidities and operative factors were analysed. Results: Sixty-five AVF and 12 CVC patients were identified. Mean age at intervention was 83.9 years and 76% of the patients were male. The majority of procedures were autogenous radio-cephalic AVF; median post-operative length of stay was 2 days. Cumulative AVF patient survival at 12 and 24 months was 82% and 72%, respectively. This was significantly better than survival rates of CVC patients, with 12-month survival of 45%. Primary patency at 6, 12 and 24 months was 58%, 39% and 31%. There were 113 follow-up procedures in 41 patients required to maintain patency. Conclusions: Although patency rates are inferior and re-intervention rates higher than in younger patients, AVF can be a durable option for RRT in selected elderly patients with improved mortality rates compared with CVC. Age alone should not preclude primary AVF placement.

scholarly journals Inflammatory Diseases Among Norwegian LRRK2 Mutation Carriers. A 15-Years Follow-Up of a Cohort

2021 ◽  
Vol 15 ◽  
Author(s):  
Jan O. Aasly
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Autosomal Dominant ◽  
Inflammatory Diseases ◽  
Carrier Status ◽  
Founder Effects ◽  
Mutation Carriers ◽  
The World

The first families with LRRK2 related Parkinson’s disease (PD) were presented around 15 years ago and numerous papers have described the characteristics of the LRRK2 phenotype. The prevalence of autosomal dominant PD varies around the world mainly depending on local founder effects. The highest prevalence of LRRK2 G2019S PD in Norway is located to the central part of the country and most families could be traced back to common ancestors. The typical Norwegian LRRK2 phenotype is not different from classical PD and similar to that seen in most other LRRK2 families. The discovery of LRRK2 PD has allowed us to follow-up multi-incident families and to study their phenotype longitudinally. In the Norwegian LRRK2 families there has been a significantly higher incidence of inflammatory diseases like multiple sclerosis and rheumatoid arthritis that seen in other PD populations. Recent studies in LRRK2 mechanisms have indicated that this protein may be crucial in initiating disease processes. In this short survey of 100 Norwegian mutation carriers followed through more than 15 years are presented. The prevalence of inflammatory diseases among these cases is highlighted. The role of LRRK2 in the conversion process from carrier status to PD phenotype is still unknown and disease generating mechanisms important for initiating LRRK2 PD are still to be identified.

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