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Nomani, Homa, Sara Saei, Thomas P. Johnston, Amirhossein Sahebkar y Amir Hooshang Mohammadpour. "The Efficacy of Anti-inflammatory Agents in the Prevention of Atrial Fibrillation Recurrences". Current Medicinal Chemistry 28, n.º 1 (29 de diciembre de 2020): 137–51. http://dx.doi.org/10.2174/1389450121666200302095103.
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: Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.
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Young, Guy, Fauke Friedrichs, Neil Goldenberg, Gili Kenet, Marilyn Manco-Johnson, Christine During y Ulrike Nowak-Gottl. "Impact of the Factor II G20210A Variant and the Factor V G1691A on Recurrent Venous Thromboembolism in Children: An International Multicentre Cohort Study." Blood 110, n.º 11 (16 de noviembre de 2007): 1641. http://dx.doi.org/10.1182/blood.v110.11.1641.1641.
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Abstract The recurrence rate of thrombosis in children following a first thrombotic event ranges from 3% in neonates to 8% in older children. The relative importance of the factor II and factor FV mutations is unknown. We present a multicentre cohort study to assess the rate of symptomatic VTE recurrence per 1000 person-years in children heterozgous for the FII and FV mutations following a first VTE. Data were pooled to increase power for the secondary aims, e.g. time to recurrence, and predictors of recurrence. Between January 1994 and December 2006, 251 consecutively enrolled VTE patients aged newborn to ≤18 years (median 5.2 years: male n=141) carrying the FII (n=61) or FV mutation (n=190) were followed for a median of 58 (max 156) months. 128 of 251 VTE patients (51%) had at least one underlying medical condition at VTE onset, and 15 were heterozygous for both mutations. Children received acute anticoagulation (AC) with unfractionated heparin or low-molecular weight heparin, followed by AC with LMWH or warfarin for a three to 6 month period in 70% of cases. Of the 251 patients enrolled, 24 (9.5%: recurrence rate of 19.3 per 1000 person-years, 95% confidence interval (CI): 12.9–28.8) had recurrent VTE at a median (min-max) of 3.5 (0.1–120) months. Not including combined defects, the recurrence rate per 1000 person-years was 41.4 (95%CI: 22.3–77) for patients with the FII mutation, and 14 (95%CI: 8.3–23.6) for carriers of the FV mutation. Median (min-max) age at recurrence was 13.4 (0.1–17) years, 12 of 24 patients were male (50%), and in 21 of 24 children (87.5%) recurrence occurred after withdrawal of AC. When comparing FII with FV subjects, Cox regression analysis showed that the factor II mutation (HR/95%CI: 2.5/1.1–5.9; p=0.031) was associated more frequently with a second VTE. In addition, older age (> 2 years) at first VTE onset (HR/95%CI: 1.1/1.01–1.14; p=0.025) independently influences the second VTE event [3.5 years (non-recurrence) vs. 12.7 years (recurrence); p< 0.0001]. Among patients suffering from recurrent VTE, 58% occurred within the first six months following VTE onset. Time to recurrence (FII vs. FII and age at onset >/< 2 ears) is shown in the Kaplan Meier analyses. The overall VTE recurrence rate of 9.5% is within the range recently reported in children. However, when comparing FII and FV carriers, the factor II G20210A variant is more often associated with a recurrent VTE. In addition, independently from the underlying gene mutation age > 2 years at first VTE increase the risk of a second symptomatic venous thrombosis. Figure Figure
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Munguti, Cecilia, Miriam Claire Mutebi, Mukuhi Ng'ang'a y Ronald Wasike. "Breast cancer recurrence rate in patients treated for early breast cancer." Journal of Clinical Oncology 38, n.º 15_suppl (20 de mayo de 2020): e12508-e12508. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e12508.
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e12508 Background: Recurrence rates for early breast cancer vary in different studies from 7% to 18%. Recurrent breast cancer is associated with poorer outcome and higher mortality rates. The recurrence rate in the Kenyan population remains unknown despite high prevalence of known risk factors. Methods: Single institution retrospective study of all women (18 -75 years) treated for early breast cancer at a single center private tertiary unit from 2009 to 2017. Results: 239 patient records were reviewed. The mean age at diagnosis was 51 (SD13.1). 98% of women presented with a palpable breast lesion. The molecular sub-type’s prevalence was: ER/PR+ (76%), triple negative (12.1%), HER2+ (2.9%). The overall recurrence rate was 7.2%, 66% recurrences were loco-regional, while 27% were metastatic disease, with 61% of the recurrences being detected initially on clinical/ self-breast examination. 77% of the recurrences were in women with ER/PR+ molecular sub-types. Recurrences in women with DCIS (2/27) were invasive breast cancers. There were no identified risk factors on uni-variate and multivariate regression analysis which conferred a risk of breast cancer recurrence. Discussion: The mean age at diagnosis in this group is younger than the western average (65 - 75 years). Majority of the women presented with symptoms – a presentation that differs from that of countries with a national breast cancer screening program. The molecular distribution of breast cancers is comparable to western populations. Conclusions: Recurrence rate for early breast cancer in this series is 7.2%, which is comparable with documented western data, with majority of the recurrences being detected initially on clinical/self-breast examination.
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Chen, Jie, Hui Qiu, Rui Chen, Jiani Huang, Liang Chen, Juncheng Wan, Qi Chen y Longzhen Zhang. "Peritumor Edema Serves as an Independent Predictive Factor of Recurrence Patterns and Recurrence-Free Survival for High-Grade Glioma". Computational and Mathematical Methods in Medicine 2022 (27 de julio de 2022): 1–10. http://dx.doi.org/10.1155/2022/9547166.
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Objective. This study is aimed at analyzing the factors affecting the recurrence patterns and recurrence-free survival (RFS) of high-grade gliomas (HGG). Methods. Eligible patients admitted to the Affiliated Hospital of Xuzhou Medical University were selected. Subsequently, the effects of some clinical data including age, gender, WHO pathological grades, tumor site, tumor size, clinical treatments, and peritumoral edema (PTE) area and molecular markers (Ki-67, MGMT, IDH-1, and p53) on HGG patients’ recurrence patterns and RFS were analyzed. Results. A total number of 77 patients were enrolled into this study. After analyzing all the cases, it was determined that tumor size and tumor site had a significant influence on the recurrent patterns of HGG, and PTE was an independent predict factor of recurrence patterns. Specifically, when the PTE was mild (<1 cm), the recurrence pattern tended to be local; in contrast, HGG was more likely to progress to marginal recurrence and distant recurrence. Furthermore, age and PTE were significantly associated with RFS; the median RFS of the population with PTE < 1 cm (23.60 months) was obviously longer than the population with PTE ≥ 1 cm (5.00 months). Conclusions. PTE is an independent predictor of recurrence patterns and RFS for HGG. Therefore, preoperative identification of PTE in HGG patients is crucially important, which is helpful to accurately estimate the recurrence pattern and RFS.
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Huybrechts, S., A. Chivet, A. Tauziede-Espariat, C. Rossoni, E. Indersie, P. Varlet, S. Puget et al. "P14.99 Clinical and biologic features predictive of survival after relapse of childhood medulloblastoma". Neuro-Oncology 21, Supplement_3 (agosto de 2019): iii91. http://dx.doi.org/10.1093/neuonc/noz126.334.
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Abstract BACKGROUND Salvage therapy for recurrent medulloblastoma (MB) is not standardized. Factors associated with survival after recurrence have not been reported. MATERIAL AND METHODS Medical records were reviewed for 155 consecutive patients with newly diagnosed MB between 2007 and 2017, treated at Gustave Roussy and Hospital Necker. The following variables were collected for all patients: age at diagnosis, stage, histology (central review according to WHO 2016 classification), molecular subgrouping (DNA methylation), first-line treatment modalities, time to relapse, pattern of recurrence and current status. RESULTS A disease recurrence was observed in 47 patients (30%) at a median time of 15 months (range, 1–88 months). The 1-year survival after recurrence was 44% (CI 95%,29.6 to 58.8). The pattern of recurrence was local in 9 patients, metastatic in 21 and combined local and metastatic in 17 patients. The time to first recurrence, less or more than 12 months from diagnosis, was a predictor of post-recurrence overall survival (p < 0.0001) after adjustment for age, treatment, MYC amplification and molecular subgroups. Twenty-seven patients (57%) experiencing recurrent or progressive disease more than 12 months after diagnosis, had an estimated 1-year survival after recurrence of 100% (CI 95%, 100.0 to 100.0) vs 30% (CI 95%, 12.2 to 50.1) with an earlier recurrence. Early relapse was more frequent in children younger than 5 years of age at diagnosis (75% vs 37%, p =0.009), anaplastic/large cell MB (30% vs 3.7%, p=0.046) and Group 3 tumours (76.5% vs 20.8%, p=0.003). Other factors influencing post-relapse survival were metastatic disease and treatment modalities at diagnosis. Multivariable analyses will be presented. CONCLUSION The overall prognosis after relapse remains poor. Time to relapse is a significant prognostic factor for postrelapse survival and may help in the design of clinical trials evaluating new agents.
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Chintagumpala, Murali, Colton Terhune, Lin Tong, Eric Bouffet, Ute Bartels, Michael Fisher, Tim Hassall et al. "MBCL-26. FACTORS ASSOCIATED WITH LONGER SURVIVAL AFTER FIRST RECURRENCE IN MEDULLOBLASTOMA BY MOLECULAR SUBGROUP AFTER RISK-BASED INITIAL THERAPY". Neuro-Oncology 22, Supplement_3 (1 de diciembre de 2020): iii394. http://dx.doi.org/10.1093/neuonc/noaa222.502.
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Abstract OBJECTIVE To evaluate differences in time to recurrence among molecular subgroups of medulloblastoma treated on a single protocol and to identify factors associated with survival after first recurrence. METHODS Time to recurrence following SJMB03 treatment was compared across methylation subgroups among relapsed patients. Therapies received subsequent to relapse were noted. Kaplan-Meier methods and log-rank tests were used for statistical analyses. RESULTS 74 of 330 medulloblastoma patients developed recurrence after initial therapy. (38 Standard-Risk; 36 High-Risk). The 2- and 5-year survival after first recurrence was 30.4% and 14.6% respectively. DNA methylation-based subgroups from initial diagnosis were SHH (n=14), Group 3 (n=24), Group 4 (n=26), and unclassified (n=8). None of the pts with WNT MB had recurrent disease. Median time to first recurrence was 1.23, 0.91, and 3.09 years in SHH, Group3, and Group 4 respectively. Group 4 patients had longer post-recurrence survival than others (p-value=0.0169). Clinical risk at diagnosis (p-value=0.337), anaplasia (p-value=0.4032), TP53 (p-value=0.1969), MYC (p-value=0.8967), and MYCN (p value = 0.9404) abnormalities were not associated with post progression survival. Patients who received any therapeutic modality (chemotherapy, re-radiation and second surgery) had longer survival and those who had all three (n=10) had the best outcome (p-value<0.0001). CONCLUSION Outcome after recurrence in medulloblastoma is dismal, however, association with subgroups is still present. Group 4 patients had a longer time to recurrence and post progression survival. No other prognostic factor at initial diagnosis was associated with outcome after recurrence. Patients who received all 3 types of conventional therapy had better survival.
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Yekedüz, Emre, Ömer Dizdar, Neyran Kertmen y Sercan Aksoy. "Comparison of Clinical and Pathological Factors Affecting Early and Late Recurrences in Patients with Operable Breast Cancer". Journal of Clinical Medicine 11, n.º 9 (22 de abril de 2022): 2332. http://dx.doi.org/10.3390/jcm11092332.
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In this study, we aimed to assess clinicopathological factors affecting early and late recurrences in patients with operable breast cancer. Patients with early (≤5 years) and late (>5 years) recurrences were assessed. Prognostic factors for disease-free survival (DFS) were also evaluated in patients with recurrence. A total of 854 patients were included. There were 432 and 205 patients in the early and late recurrence groups, respectively. In multivariate analyses, HER2+ disease, lymph node metastasis, lymphovascular invasion (LVI), and high tumor grade were associated with increased risk of early recurrence, while HER2+ disease and LVI were associated with decreased risk of late recurrence. In multivariate analyses, presence of HER2+ disease and triple-negative breast cancer (TNBC) were poor prognostic factors for DFS in patients with early recurrence. Presence of LVI and perineural invasion (PNI) were poor prognostic factors for DFS in patients with late recurrence. Molecular subtypes and LVI were effective on the early and late recurrences. However, lymph node positivity and grade were only associated with the early recurrence. After 5 years, LVI and PNI were the prognostic factors for DFS.
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Agrawal, V. y N. Bharti. "Alterations in Expression of Cell Surface and Cell Cycle Signaling Molecules in Recurrent Nonmuscle Invasive Bladder Cancers: A Tissue Microarray Expression Analysis". Journal of Global Oncology 4, Supplement 2 (1 de octubre de 2018): 94s. http://dx.doi.org/10.1200/jgo.18.60400.
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Background: Nonmuscle invasive bladder cancers (NMIBC) are one of the most common urological cancers having a high risk of recurrence and progression. Recurrent tumors may acquire certain molecular alterations responsible for progression of the tumors. Identification of these alterations is important to understand the pathobiology and guide further management. Aim: We studied the differences in expression of cell surface proteins and cell cycle signaling molecules in primary and recurrent NMIBC by immunohistochemistry (IHC) on tissue microarrays (TMA). Methods: Using FFPE tissue, TMA of 82 tumors (40 primary NMIBC and 47 recurrences) were constructed. IHC for growth factor receptors [epidermal growth factor receptor (EGFR), HER2/neu and FGFR3], cell adhesion molecules (E-cadherin and beta-catenin) and cell cycle pathway molecules (p53, p21/WAF1/Cip1 and Ki-67 proliferation index) was performed. A semiquantitative H-score (Histo-score; range 0-300) was calculated according to the intensity (0, negative; 1, weak; 2, moderate; and 3, strong) and percentage of cells stained. < 10% cells showing nuclear p21 expression was considered p21-loss. The differences in expression between the primary and recurrent tumors were analyzed using paired t test. Results: The mean age at presentation was 65.3 ± 13.6 years with a male predominance (n=36). The mean time to recurrence was 33.4 months (range 3-109). Progression in grade and/or stage was seen in 30 (75%) tumors. Time to recurrence was shorter in primary tumors with ≥ 5% Ki-67 proliferation index. There was no significant difference in expression of cell surface proteins between primary and recurrent tumors. Significant p21 loss was seen in recurrent tumors ( P = 0.03) and significantly correlated with loss of surface beta-catenin and nuclear p53 positivity ( P = 0.002). Ki-67 index was higher in recurrent tumors and also correlated with p53 positivity ( P = 0.007). Conclusion: We found no significant differences in expression of cell surface molecules in primary nonmuscle invasive bladder cancers and their recurrences. However, there were significant alterations in expression of molecules of cell cycle signaling pathway and cellular proliferation in recurrent tumors suggesting the role of cell cycle regulators as promising targets in these cancers.
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Voduc, K. David, Maggie C. U. Cheang, Scott Tyldesley, Karen Gelmon, Torsten O. Nielsen y Hagen Kennecke. "Breast Cancer Subtypes and the Risk of Local and Regional Relapse". Journal of Clinical Oncology 28, n.º 10 (1 de abril de 2010): 1684–91. http://dx.doi.org/10.1200/jco.2009.24.9284.
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Purpose The risk of local and regional relapse associated with each breast cancer molecular subtype was determined in a large cohort of patients with breast cancer. Subtype assignment was accomplished using a validated six-marker immunohistochemical panel applied to tissue microarrays. Patients and Methods Semiquantitative analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin (CK) 5/6 was performed on tissue microarrays constructed from 2,985 patients with early invasive breast cancer. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype–nonbasal. Multivariable Cox analysis was used to determine the risk of local or regional relapse associated the intrinsic subtypes, adjusting for standard clinicopathologic factors. Results The intrinsic molecular subtype was successfully determined in 2,985 tumors. The median follow-up time was 12 years, and there have been a total of 325 local recurrences and 227 regional lymph node recurrences. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67 < 1%) had the best prognosis and the lowest rate of local or regional relapse. For patients undergoing breast conservation, HER2-enriched and basal subtypes demonstrated an increased risk of regional recurrence, and this was statistically significant on multivariable analysis. After mastectomy, luminal B, luminal-HER2, HER2-enriched, and basal subtypes were all associated with an increased risk of local and regional relapse on multivariable analysis. Conclusion Luminal A tumors are associated with a low risk of local or regional recurrence. Molecular subtyping of breast tumors using a six-marker immunohistochemical panel can identify patients at increased risk of local and regional recurrence.
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Kim, Yong Chan, Heun Choi, Young Ah Kim, Yoon Soo Park, Young Hee Seo, Hyukmin Lee y Kyungwon Lee. "Risk factors and microbiological features of recurrent Escherichia coli bloodstream infections". PLOS ONE 18, n.º 1 (10 de enero de 2023): e0280196. http://dx.doi.org/10.1371/journal.pone.0280196.
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Understanding the risk factors and microbiological features in recurrent Escherichia coli BSI is helpful for clinicians. Data of patients with E. coil BSI from 2017 to 2018 were collected. Antimicrobial resistance rates of E. coli were determined. We also identified the ST131 and ESBL genotype to evaluate the molecular epidemiology of E. coli. Whole genome sequencing was conducted on the available ESBL-producing E. coli samples. Of 808 patients with E. coli BSI, 57 (6.31%) experienced recurrence; 29 developed at 4–30 days after initial BSI (early onset recurrence) and 28 at 31–270 days after initial BSI (late onset recurrence). One hundred forty-nine patients with single episode, whose samples were available for determining the molecular epidemiology, were selected for comparison. Vascular catheterization (adjusted odds ratio [aOR], 4.588; 95% confidence interval [CI], 1.049–20.068), ESBL phenotype (aOR, 2.037; 95% CI, 1.037–3.999) and SOFA score ≥9 (aOR, 3.210; 95% CI, 1.359–7.581) were independent risk factors for recurrence. The proportion of ST131 and ESBL genotype was highest in early onset recurrent BSI (41.4% and 41.4%, respectively), from which E. coil had the highest resistance rates to most antimicrobial agents. Whole genome sequencing on 27 of ESBL-producing E. coli (11 from single episode, 11 from early onset recurrence, and 5 from late onset recurrence) demonstrated that various virulence factors, resistant genes, and plasmid types existed in isolates from all types of BSI. Risk factors contributing to the recurrence and microbiological features of E. coli causing recurrent BSI may be helpful for management planning in the clinical setting.
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Nathan, Cherie-Ann O., Scott Franklin, Fleurette W. Abreo, Raja Nassar, Arrigo De Benedetti y Jonathan Glass. "Analysis of Surgical Margins With the Molecular Marker eIF4E: A Prognostic Factor in Patients With Head and Neck Cancer". Journal of Clinical Oncology 17, n.º 9 (septiembre de 1999): 2909. http://dx.doi.org/10.1200/jco.1999.17.9.2909.
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PURPOSE: Complete excision of cancer is guided by histologic assessment of surgical margins. Molecular markers may be more sensitive in identifying malignant cells. eIF4E, a eukaryotic protein synthesis initiation factor, is found elevated in all head and neck squamous cell cancers (HNSCC). In a preliminary study using Western blots and a retrospective study using immunohistochemistry, eIF4E elevation in histologically tumor-free surgical margins correlated with a higher local-regional recurrence. We wanted to confirm this hypothesis in a prospective study. PATIENTS AND METHODS: Immunohistochemical analysis of surgical margins and tumors with an antibody to eIF4E was performed on all newly diagnosed HNSCC patients who underwent surgical resection for their disease between January 1996 and December 1997. RESULTS: All 65 patients had elevated levels of eIF4E in the tumors. Thirty-six patients (55%) had elevated eIF4E in histologically tumor-free margins, and 20 of these patients (56%) have had local-regional recur- rrences. Twenty-nine patients (45%) had no elevation of eIF4E in the margins, and only two of these patients (6.9%) have had recurrences. Cox regression analysis showed that elevated eIF4E in the margins was an independent prognostic factor (P = .009) for recurrence. The Kaplan-Meier curves for the probability of nonrecurrence were significantly different for positive and negative eIF4E margins (P = .0001, log-rank test). CONCLUSION: In histologically tumor-free surgical margins, elevated levels of eIF4E predict a significantly increased risk of recurrence. Elevated levels of eIF4E in tumor margins may identify patients who could benefit from additional therapy.
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Guk, Mykola O., Mykhailo B. Bandrivskyi, Olena O. Danevych, Artur O. Mumlev, Dmitry M. Tsyurupa, Andrey A. Chukov y Vasyl V. Kondratyuk. "Modern views on the recurrence of meningiomas". Ukrainian Neurosurgical Journal 28, n.º 2 (24 de junio de 2022): 3–7. http://dx.doi.org/10.25305/unj.243332.
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Meningiomas are common tumors of the central nervous system. Grade I meningiomas are generally considered to be "benign". However, a certain percentage of these tumors have a more aggressive course, similar to malignant tumors. Numerous observations have shown that even in the case of radical removal of the tumor, the latter recur within the next 10 years. Recent molecular studies have shed new light on meningioma subtypes, their behavior, the prospect of new treatment, and prognostic features for patients. The study of V.E. Clark et al. found a number of mutations in NF2 meningiomas, namely TRAF7 (tumor necrosis factor receptor 7 factor), KLF4 (Kruppel-like factor 4c), AKT1 and SMO. The pattern between the type of mutation and the tumor location was established: posterior cranial fossa, parasagittal area, falx, torculae and intraventricular sections - loss of NF2 or chromosome 22, olfactory groove and middle cranial fossa - KLF4 / TRAF7, olfactory groove, - PIK3CA, middle parts of the anterior cranial fossa and middle cranial fossa - AKT1 / POLR2, olfactory groove - SMO. The selection criteria in the study, which analyzed data from 469 meningiomas of a known molecular subgroup, were the degree of resection, postoperative irradiation, postoperative neuroimaging and time to recurrence (if present). Molecular subgroups of meningiomas had different clinical manifestations during the two years of follow-up, with several aggressive subgroups (NF2, PI3K, HH, TRAF7) recurring at an average rate 22 times faster than less aggressive tumors (KLF4, POLR2A, SMARCB1). PI3K-activated meningiomas recurred earlier than tumors in other groups. The potentially more aggressive group of meningiomas with HH, NF2, and TRAF7 mutations demonstrated a high recurrence rate after 60 months of follow-up (35.3, 43.7, and 36.4%, respectively), whereas most tumor recurrences with PI3K mutations were reported within the first 24 months (75,0%). Classification of meningiomas by genomic mutations is a promising tool. Its introduction into clinical practice will make it possible to predict the aggressiveness of meningiomas and the risk of their recurrence, which will help to give a more accurate prognosis for patients and develop effective therapeutic methods for these tumors.
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Wu, Cheng-Tien, Ting-Hua Yang, Man-Chih Chen, Yao-Pang Chung, Siao-Syun Guan, Lin-Hwa Long, Shing-Hwa Liu y Chang-Mu Chen. "Low Intensity Pulsed Ultrasound Prevents Recurrent Ischemic Stroke in a Cerebral Ischemia/Reperfusion Injury Mouse Model via Brain-derived Neurotrophic Factor Induction". International Journal of Molecular Sciences 20, n.º 20 (18 de octubre de 2019): 5169. http://dx.doi.org/10.3390/ijms20205169.
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The incidence of stroke recurrence is still higher despite the advanced progression of therapeutic treatment and medical technology. Low intensity pulsed ultrasound (LIPUS) has been demonstrated to possess therapeutic effects on neuronal diseases and stroke via brain-derived neurotrophic factor (BDNF) induction. In this study, we hypothesized that LIPUS treatment possessed therapeutic benefits for the improvement of stroke recurrence. Adult male C57BL/6J mice were subjected to a middle cerebral artery occlusion (MCAO) surgery and then followed to secondary MCAO surgery as a stroke recurrence occurred after nine days from the first MCAO. LIPUS was administered continuously for nine days before secondary MCAO. LIPUS treatment not only decreased the mortality but also significantly moderated neuronal function injury including neurological score, motor activity, and brain pathological score in the recurrent stroke mice. Furthermore, the administration of LIPUS attenuated the apoptotic neuronal cells and increased Bax/Bcl-2 protein expression ratio and accelerated the expression of BDNF in the brain of the recurrent stroke mice. Taken together, these results demonstrate for the first time that LIPUS treatment arouses the expression of BDNF and possesses a therapeutic benefit for the improvement of stroke recurrence in a mouse model. The neuroprotective potential of LIPUS may provide a useful strategy for the prevention of a recurrent stroke.
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Urup, T., A. K. Trip, S. B. Chiranth, I. J. Christensen, K. Grunnet, S. Møller, B. Hasselbalch, A. Muhic, U. Lassen y H. S. Poulsen. "P11.32.A EGFR expression and non-methylated MGMT predict distant recurrence in glioblastoma patients treated with standard therapy". Neuro-Oncology 24, Supplement_2 (1 de septiembre de 2022): ii64. http://dx.doi.org/10.1093/neuonc/noac174.221.
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Abstract Background Infiltrative growth within the central nervous system is hallmark of glioblastoma (GBM) at time of diagnosis. Targeting infiltrative glioma cells by adding chemotherapy to local treatment (surgical resection and radiotherapy) has led to improved tumor control and survival. Still, infiltrative growth is a major factor in therapeutic failure and tumor recurrence is almost inevitable. Herein, we hypothesize that distant recurrence represents a more migratory phenotype and that biomarkers associated with distant recurrence can be used to personalize the treatment. The aim of this study was to identify clinical and molecular factors associated with distance recurrence in glioblastoma patients treated with standard therapy. Material and Methods A prospective cohort of consecutive, non-selected GBM patients administered standard therapy as primary treatment between 2005-2020 at Rigshospitalet, Copenhagen, Denmark. Distant recurrence was defined as a new contrast-enhancing tumor lesion outside the radiation field (> 2 cm from the gross tumor volume). Clinical and molecular factors were screened for association with time to distant recurrence (p < 0.30) using univariate analysis. The final model was generated employing multivariate Cox regression analysis to model the association with time to distant recurrence. It was chosen to maintain known prognostic factors in the model and subsequently add significantly associated factors (p < 0.05). Competing risk adjusted analysis were performed with death as a competing risk. Results A total of 897 patients were included and at a median follow-up time of 73 (range: 12-198) months, 733 patients were evaluable for recurrence pattern. Out of 733 patients, 146 patients (20%) had distant recurrence. Median time to tumor progression was 7.0 months for patients with a local recurrence and 8.0 months for those with a distant recurrence (p=0.31). The following prognostic factors were not associated with distant recurrence by multivariate analysis: Corticosteroid use (p=0.84), age (p=0.20), multifocal disease (p=0.81), ECOG performance status (p=0.99) and degree of tumor resection (p=0.20). In multivariate analysis, factors independently associated with a higher likelihood of distant recurrence were: Non-methylated promoter of the MGMT gene (HR=1.93; 95% CI: 1.27-2.95; p=0.002) and positive expression of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry (HR=3.70; 95% CI: 1.61-8.33; p=0.002). Conclusion Non-methylated MGMT and positive expression of EGFR were independently associated with a higher likelihood of distant recurrence in GBM patients treated with standard-of-care. These factors, if validated, can be used for risk stratification and to enrich clinical treatment protocols aiming at improved local or distant tumor control.
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Ryabova, A. I., V. A. Novikov, N. V. Yunusova, A. A. Ponomareva, L. V. Spirina y O. V. Gribova. "The role of extracellular vesicles in the diagnosis of glioblastoma progression". Advances in Molecular Oncology 7, n.º 3 (24 de noviembre de 2020): 8–18. http://dx.doi.org/10.17650/2313-805x-2020-7-3-8-18.
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The article reviews studies highlighting the role of extracellular molecules in non-invasive diagnosis of glioblastoma recurrence. Glioblastoma is the most common malignant tumor of the brain characterized by fatal outcome prognosis. Current treatment of tumor recurrence allows to increase patient survival, improve functional outcome and decrease caregivers» load. The standard method of recurrence diagnosis is neuroimaging which at early stages cannot distinguish between tumor recurrence and post-radiation changes. Currently in oncology, liquid biopsy and marker detection in circulating extracellular vesicles are considered promising approaches allowing to obtain early and differential tumor diagnosis, determine dynamic molecular and genetic status of the tumor, diagnose tumor recurrence at early stages. In this context, the most promising approach to glioblastoma diagnosis is associated with studying of expression of glial fibrillary acidic protein (GFAP), epidermal growth factor receptor (EGFR), its mutant variant EGFRvIII, podoplanin (PDPN) and isocitrate dehydrogenase 1 (IDH1) in extracellular vesicles; for primary glioblastoma diagnosis and early recurrence: studying of microRNA-210, -301a, -222, -123-3p, -21; for control of immunotherapy effectiveness in patients with recurrent forms of glioblastoma after standard treatment: evaluation of СD9+ / GFAP+ / survivin+ exosomes in plasma.
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Speranza, G., V. Cohen, J. S. Agulnik, G. Chong, F. Meilleur, G. Brandao, G. Kasymjanova, D. Small y W. H. Miller. "Molecular changes in epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) biopsies at time of progression compared to initial biopsy". Journal of Clinical Oncology 27, n.º 15_suppl (20 de mayo de 2009): e22066-e22066. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22066.
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e22066 Background: EGFR mutations predict sensitivity and clinical outcome to tyrosine kinase inhibitors (TKI) in NSCLC. The two most commonly described mutations are Exon 19 deletion and Exon 21 L858R missense mutations. Genetic alterations over time have been described in other tumour types, but studies assessing EGFR genotypic changes with lung cancer progression are lacking. We sought to compare EGFR mutational status from lung tumors at time of recurrence or progression with the primary tumor. Methods: Using the Jewish General Hospital lung cancer database, of all patients diagnosed with NSCLC since 1999, those with biopsies at two different points in time were identified. All tumour samples were genotyped for EGFR exons 19 and 21 mutations using denaturing high performance liquid chromatography (dHPLC). Results: 29 patients were identified. Data for 12 patients, whose time of recurrence or progression varied between 4 months and 6 years, are available at this time. Of 12 patients, one had EGFR exon 19 mutation at time of diagnosis. One patient who initially displayed no EGFR mutation was found to have an exon 19 deletion at time of recurrence. The one with exon 19 at time of initial diagnosis continued to express exon 19 in the second biopsy. Conclusions: To our knowledge, this is the only study assessing changes in molecular genotype using dHPLC between primary and recurrent or progressive lung cancer biopsy specimens. Although sample size is small, it is evident that changes in EGFR mutational status can occur. Further prospective studies are required to determine how commonly molecular changes occur. No significant financial relationships to disclose.
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Teng, Chiao-Fang, Tsai-Chung Li, Hsi-Yuan Huang, Wen-Ling Chan, Han-Chieh Wu, Woei-Cherng Shyu, Ih-Jen Su y Long-Bin Jeng. "Hepatitis B virus pre-S2 deletion (nucleotide 1 to 54) in plasma predicts recurrence of hepatocellular carcinoma after curative surgical resection". PLOS ONE 15, n.º 11 (25 de noviembre de 2020): e0242748. http://dx.doi.org/10.1371/journal.pone.0242748.
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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Despite curative surgical resection, high recurrence of HCC after surgery results in poor patient survival. To develop prognostic markers is therefore important for better prevention and therapy of recurrent HCC to improve patient outcomes. Deletion mutations over the pre-S1 and pre-S2 gene segments of hepatitis B virus (HBV) have been closely associated with recurrence of HCC after curative surgical resection. In this study, we applied a next-generation sequencing-based approach to further evaluate the association of pre-S deletion regions with HCC recurrence. We demonstrated that the pre-S2 deletion (nucleotide 1 to 54) was the most predominant deletion regions of pre-S gene in plasma of HBV-related HCC patients. Moreover, patients with the pre-S2 deletion (nucleotide 1 to 54) exhibited a significantly higher risk of HCC recurrence after curative surgical resection than those without. The pre-S2 deletion (nucleotide 1 to 54) in plasma represented a prognostic factor that independently predicted HCC recurrence with greater performance than other clinicopathological and viral factors. Our data suggest that detection of the pre-S2 deletion (nucleotide 1 to 54) in plasma may be a promising noninvasive strategy for identifying patients at high risk for HCC recurrence after curative surgical resection.
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Young, Annie M., Andrea Marshall, Jenny Thirlwall, Oliver Chapman, Anand Lokare, Catherine Hill, Danielle Hale et al. "Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D)". Journal of Clinical Oncology 36, n.º 20 (10 de julio de 2018): 2017–23. http://dx.doi.org/10.1200/jco.2018.78.8034.
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Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.
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Nakanishi, Koki, Mitsuro Kanda, Shinichi Umeda, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada et al. "Prediction of peritoneal recurrences of gastric cancer by qPCR analysis of peritoneal lavage fluids." Journal of Clinical Oncology 37, n.º 4_suppl (1 de febrero de 2019): 52. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.52.
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52 Background: Peritoneal lavage cytology has been regarded as the only reliable method detect free cancer cells in the abdominal cavity. However, there certainly are patients who experience peritoneal recurrences despite negative cytology. Methods: Using qRT-PCR analysis, mRNA levels of 9 candidate molecular markers were quantified in peritoneal lavage fluids of from 187 patients with gastric cancer and 30 benign disease controls. ROC curve analysis was conducted to compare accuracies of the candidate markers. The cut-off points were set at the highest values of the benign disease controls. We evaluated predictive values of molecular markers in peritoneal lavage fluids for peritoneal recurrence. Results: From the result of ROC curve analysis, synaptotagmin XIII ( SYT13) and carcinoembryonic antigen ( CEA) mRNA levels were identified as predictive markers for peritoneal recurrences (The AUC value, 0.771, 0.775, respectively). 162 patients who had no concomitant peritoneal metastasis and were negative for lavage cytology (P0CY0), 13 patients (8.2%) had peritoneal recurrences. Those with either positive SYT13 or CEA mRNA level in peritoneal lavage fluids had significantly shorter peritoneal recurrence-free survival times compared to those with negative (3-years peritoneal recurrence-free survival rates, 69.5% vs 95.6%; P = 0.0069 and 79.3% vs. 93.4%; P = 0.0211, respectively). By combination of SYT13 and CEA, patients with both markers-positive had the greatest prevalence of peritoneal recurrences. Moreover, the peritoneal recurrence free survival curves of the both markers-positive group approached to that of the positive for lavage cytology group. Univariate analysis revealed that both SYT13-positive and CEA-positive were prognostic factors for peritoneal recurrence (hazard ratio: 4.21 and 3.53, respectively). In the multivariable analysis, SYT13-positive was found to be statistically significant independent prognostic factors (hazard ratio: 3.84, 95% confidence interval 1.24-13.2, P = 0.0202). Conclusions: SYT13 and CEA levels in peritoneal lavage fluids accurately predict peritoneal recurrences in patients with P0CY0.
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Corinaldesi, Giorgio y Christian Corinaldesi. "High Plasma Levels of Factor VIII and Factor IX Increased the Incidence of Recurrent VTE." Blood 114, n.º 22 (20 de noviembre de 2009): 5070. http://dx.doi.org/10.1182/blood.v114.22.5070.5070.
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Abstract Abstract 5070 The aim of this study was to evaluate the diagnostic accurancy of the measurement of procoagulant factors FVIII and FIX levels and the risk of recurrence of venous thromboembolism (VTE). We have studied 56 patients (14 male, 42 female) with an objectively diagnosis of first deep vein thrombosis enrolled from February 2003 to February 2008, all patients were <60 years, without known malignancies, heart failure, chronic lung disease, infection, recent surgery, or genetic defects as Factor V Leiden (FV-Arg 506 Glu), prothrombin G20210A, deficiencies of Protein S or C or ATIII, hyperhomocysteinemia, dysfibrinogenemias; with increased levels of FVIII (>218 IU/dl), and FIX (>136 UI/dl). FVIII and FIX antigen levels were measured by ELISA. All patients received subcutaneous low molecular-weight eparin as thromboprophylactic treatment for the first 3 month after primary VTE, color Doppler ultrasonography (DUS) was performed periodically after primary VTE, the venous hemodynamic parameters studied included: blood flow velocity (cm/sec), vein cross sectional area (cm/2) blood volume flow (ml/sec), and microvascular injury was evaluated. Our studies have confirmed that a markedly elevated plasma levels of FVIII >256 IU/dl (range 218-294), and FIX >164IU/dl (range 136-192) among the patients with first episode of VTE are independent predictors of early recurrence about 52-74%: these patients have increased fibrin formation, D-Dimer levels (234.6ng/ml), and blood rheologic variables such as plasma viscosity are still present in all patients: plasma viscosity mPa/s shear rate >1.98 and blood viscosity mPa/s shear rate >3.48 especially under low shear conditions. These factors show to be associated with VTE and above all with the recurrence (54 patients), and emerged as relatively independent of other thrombophilic factors. The higt risk of VTE recurrence in these patients requires strategies for its prevention: secondary prophylaxis with the administration of standard oral anticoagulant at moment the use of coumarins (INR: 2.0-3.0) and possibly the need for prolonged, probably life-long treatment. Disclosures No relevant conflicts of interest to declare.
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Donadini, Marco P., Francesco Dentali, Samuela Pegoraro, Fulvio Pomero, Chiara Brignone, Luigina Guasti, Luigi Steidl y Walter Ageno. "Long-term recurrence of venous thromboembolism after short-term treatment of symptomatic isolated distal deep vein thrombosis: A cohort study". Vascular Medicine 22, n.º 6 (21 de julio de 2017): 518–24. http://dx.doi.org/10.1177/1358863x17720531.
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Isolated distal deep vein thrombosis (IDDVT) is a common clinical manifestation of venous thromboembolism (VTE). However, there are only scant and heterogeneous data available on the long-term risk of recurrent VTE after IDDVT, and the optimal therapeutic management remains uncertain. We carried out a retrospective cohort study of consecutive patients diagnosed with symptomatic IDDVT between 2004 and 2011, according to a predefined short-term treatment protocol (low molecular weight heparin (LMWH) for 4–6 weeks). The primary outcome was the occurrence of recurrent VTE. A total of 321 patients were enrolled. IDDVT was associated with a transient risk factor or cancer in 165 (51.4%) and 56 (17.4%) patients, respectively. LMWH was administered for 4–6 weeks to 280 patients (87.2%), who were included in the primary analysis. Overall, during a mean follow-up of 42.3 months, 42 patients (15%) developed recurrent VTE, which occurred as proximal DVT or PE in 21 cases. The recurrence rate of VTE per 100 patient-years was 3.5 in patients with transient risk factors, 7.2 in patients with unprovoked IDDVT, and 5.9 in patients with cancer ( p=0.018). At multivariable analysis, unprovoked IDDVT and previous VTE were significantly associated with recurrent VTE (HR 2.16, 95% CI 1.12–4.16 and HR 1.97, 95% CI 1.01–3.86, respectively). In conclusion, the long-term risk of recurrent VTE after IDDVT treated for 4–6 weeks is not negligible, in particular in patients with unprovoked IDDVT or cancer. Further studies are needed to clarify whether a longer, but definite treatment duration effectively prevents these recurrences.
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Choi, Seung Won. "BIOM-06. MOLECULAR SIGNATURES UNDERLIE THE DISTINCT FAILURE PATTERNS OF MALIGNANT GLIOMAS". Neuro-Oncology 23, Supplement_6 (2 de noviembre de 2021): vi10—vi11. http://dx.doi.org/10.1093/neuonc/noab196.037.
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Abstract BACKGROUND Malignant gliomas exhibit varied failure patterns upon recurrence; however, genomic backgrounds of these distinct phenotypes have not been evaluated. We aimed to explore the genomic traits associated with distinct failure patterns in malignant glioma patients. METHODS This study involved 272 malignant glioma patients. Failure pattern was defined for the spatial relationship between recurrent tumor and the original tumor as follows: local recurrence (LR), remote recurrence, leptomeningeal seeding (LMC), and combined failure pattern. Molecular characteristics underlying different failure patterns were investigated for the mutation profile, copy number variation (CNV), and transcriptomic signatures. RESULTS Local recurrence was the most prominent failure pattern (62.9%), followed by combined recurrence (22.8%). Multivariate Cox regression analysis confirmed failure pattern as one of the independent prognostic factors. Patients with combined failure patterns exhibited the worst prognoses, whereas patients with remote recurrence exhibited the most favorable outcomes (median overall survival = 11.4 and 25.2 months, respectively). In IDH1-wild type glioblastoma (GBM) patients, TERT and PIK3CA mutation were significantly associated with the development of combined failure pattern and leptomeningeal seeding, respectively (p-value=0.015 & p-value=0.004, respectively). Transcriptomic analysis exhibited that inter-neuronal synaptic transmission was enriched in GBMs with combined failure pattern and this finding was further validated in proteomic analysis; neuronal myelination and synaptic transmission-related pathways were upregulated in GBMs which exhibited combined failure pattern. CONCLUSIONS Collectively, we demonstrated that the inherent molecular characteristics of the tumors might contribute to the eventual relapse patterns; tracking their evolutionary pathways may unravel novel therapeutic vulnerabilities of these tumors.
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Gruttadauria, Salvatore, Floriana Barbera, Pier Giulio Conaldi, Duilio Pagano, Rosa Liotta, Enrico Gringeri, Roberto Miraglia et al. "Clinical and Molecular-Based Approach in the Evaluation of Hepatocellular Carcinoma Recurrence after Radical Liver Resection". Cancers 13, n.º 3 (29 de enero de 2021): 518. http://dx.doi.org/10.3390/cancers13030518.
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Background: Hepatic resection remains the treatment of choice for patients with early-stage HCC with preserved liver function. Unfortunately, however, the majority of patients develop tumor recurrence. While several clinical factors were found to be associated with tumor recurrence, HCC pathogenesis is a complex process of accumulation of somatic genomic alterations, which leads to a huge molecular heterogeneity that has not been completely understood. The aim of this study is to complement potentially predictive clinical and pathological factors with next-generation sequencing genomic profiling and loss of heterozygosity analysis. Methods: 124 HCC patients, who underwent a primary hepatic resection from January 2016 to December 2019, were recruited for this study. Next-generation sequencing (NGS) analysis and allelic imbalance assessment in a case-control subgroup analysis were performed. A time-to-recurrence analysis was performed as well by means of Kaplan–Meier estimators. Results: Cumulative number of HCC recurrences were 26 (21%) and 32 (26%), respectively, one and two years after surgery. Kaplan–Meier estimates for the probability of recurrence amounted to 37% (95% C.I.: 24–47) and to 51% (95% C.I.: 35–62), after one and two years, respectively. Multivariable analysis identified as independent predictors of HCC recurrence: hepatitis C virus (HCV) infection (HR: 1.96, 95%C.I.: 0.91–4.24, p = 0.085), serum bilirubin levels (HR: 5.32, 95%C.I.: 2.07–13.69, p = 0.001), number of nodules (HR: 1.63, 95%C.I.: 1.12–2.38, p = 0.011) and size of the larger nodule (HR: 1.11, 95%C.I.: 1.03–1.18, p = 0.004). Time-to-recurrence analysis showed that loss of heterozygosity in the PTEN loci (involved in the PI3K/AKT/mTOR signaling pathway) was significantly associated with a lower risk of HCC recurrence (HR: 0.35, 95%C.I.: 0.13–0.93, p = 0.036). Conclusions: multiple alterations of cancer genes are associated with HCC progression. In particular, the evidence of a specific AI mutation presented in 20 patients seemed to have a protective effect on the risk of HCC recurrence.
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Lau, Darryl, Stephen T. Magill y Manish K. Aghi. "Molecularly targeted therapies for recurrent glioblastoma: current and future targets". Neurosurgical Focus 37, n.º 6 (diciembre de 2014): E15. http://dx.doi.org/10.3171/2014.9.focus14519.
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Object Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. Methods A systematic search was performed with the phrase “(name of particular agent) and glioblastoma” as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. Results A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10–15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%–20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%–20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied. Conclusions Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.
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Takeuchi, Hiroya, Donald L. Morton, Christine Kuo, Roderick R. Turner, David Elashoff, Robert Elashoff, Bret Taback, Akihide Fujimoto y Dave S. B. Hoon. "Prognostic Significance of Molecular Upstaging of Paraffin-Embedded Sentinel Lymph Nodes in Melanoma Patients". Journal of Clinical Oncology 22, n.º 13 (1 de julio de 2004): 2671–80. http://dx.doi.org/10.1200/jco.2004.12.009.
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PurposeDetection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome.Patients and MethodsqRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family), GalNAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3).ResultsFifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1).ConclusionMolecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.
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Xu, Shaohua, Jie Zhou, Kai Liu, Zhoumiao Chen y Zhengfu He. "A Recurrence-Specific Gene-Based Prognosis Prediction Model for Lung Adenocarcinoma through Machine Learning Algorithm". BioMed Research International 2020 (7 de noviembre de 2020): 1–10. http://dx.doi.org/10.1155/2020/9124792.
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Background. After curative surgical resection, about 30-75% lung adenocarcinoma (LUAD) patients suffer from recurrence with dismal survival outcomes. Identification of patients with high risk of recurrence to impose intense therapy is urgently needed. Materials and Methods. Gene expression data of LUAD were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differentially expressed genes (DEGs) were calculated by comparing the recurrent and primary tissues. Prognostic genes associated with the recurrence-free survival (RFS) of LUAD patients were identified using univariate analysis. LASSO Cox regression and multivariate Cox analysis were applied to extract key genes and establish the prediction model. Results. We detected 37 DEGs between primary and recurrent LUAD tumors. Using univariate analysis, 31 DEGs were found to be significantly associated with RFS. We established the RFS prediction model including thirteen genes using the LASSO Cox regression. In the training cohort, we classified patients into high- and low-risk groups and found that patients in the high-risk group suffered from worse RFS compared to those in the low-risk group ( P < 0.01 ). Concordant results were confirmed in the internal and external validation cohort. The efficiency of the prediction model was also confirmed under different clinical subgroups. The high-risk group was significantly identified as the risk factor of recurrence in LUAD by the multivariate Cox analysis ( HR = 13.37 , P = 0.01 ). Compared to clinicopathological features, our prediction model possessed higher accuracy to identify patients with high risk of recurrence ( AUC = 96.3 % ). Finally, we found that the G2M checkpoint pathway was enriched both in recurrent tumors and primary tumors of high-risk patients. Conclusions. Our recurrence-specific gene-based prognostic prediction model provides extra information about the risk of recurrence in LUAD, which is conducive for clinicians to conduct individualized therapy in clinic.
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Sciubba, Daniel M., Rafael De la Garza Ramos, C. Rory Goodwin, Nancy Abu-Bonsrah, Ali Bydon, Timothy F. Witham, Chetan Bettegowda, Ziya L. Gokaslan y Jean-Paul Wolinsky. "Clinical, surgical, and molecular prognostic factors for survival after spinal sarcoma resection". Neurosurgical Focus 41, n.º 2 (agosto de 2016): E9. http://dx.doi.org/10.3171/2016.5.focus16118.
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OBJECTIVE The goal of this study was to investigate the local recurrence rate and long-term survival after resection of spinal sarcomas. METHODS A retrospective review of patients who underwent resection of primary or metastatic spinal sarcomas between 1997 and 2015 was performed. Tumors were classified according to the Enneking classification, and resection was categorized as Enneking appropriate (EA) if the specimen margins matched the Enneking recommendation, and as Enneking inappropriate (EI) if they did not match the recommendation. The primary outcome measure for all tumors was overall survival; local recurrence was also an outcome measure for primary sarcomas. The association between clinical, surgical, and molecular (tumor biomarker) factors and outcomes was also investigated. RESULTS A total of 60 patients with spinal sarcoma were included in this study (28 men and 32 women; median age 38 years). There were 52 primary (86.7%) and 8 metastatic sarcomas (13.3%). Thirty-nine tumors (65.0%) were classified as high-grade, and resection was considered EA in 61.7% of all cases (n = 37). The local recurrence rate was 10 of 52 (19.2%) for primary sarcomas; 36.8% for EI resection and 9.1% for EA resection (p = 0.010). Twenty-eight patients (46.7%) died during the follow-up period, and median survival was 26 months. Overall median survival was longer for patients with EA resection (undefined) compared with EI resection (13 months, p < 0.001). After multivariate analysis, EA resection significantly decreased the hazard of local recurrence (HR 0.24, 95% CI 0.06–0.93; p = 0.039). Age 40 years or older (HR 4.23, 95% CI 1.73–10.31; p = 0.002), previous radiation (HR 3.44, 95% CI 1.37–8.63; p = 0.008), and high-grade sarcomas (HR 3.17, 95% CI 1.09–9.23; p = 0.034) were associated with a significantly increased hazard of death, whereas EA resection was associated with a significantly decreased hazard of death (HR 0.22, 95% CI 0.09–0.52; p = 0.001). CONCLUSIONS The findings in the present study suggest that EA resection may be the strongest independent prognostic factor for improved survival in patients with spinal sarcoma. Additionally, patients who underwent EA resection had lower local recurrence rates. Patients 40 years or older, those with a history of previous radiation, and those with high-grade tumors had an increased hazard of mortality in this study.
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Kwiatkowski, D. J., D. H. Harpole, J. Godleski, J. E. Herndon, D. B. Shieh, W. Richards, R. Blanco, H. J. Xu, G. M. Strauss y D. J. Sugarbaker. "Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: clinical implications." Journal of Clinical Oncology 16, n.º 7 (julio de 1998): 2468–77. http://dx.doi.org/10.1200/jco.1998.16.7.2468.
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PURPOSE To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design a molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). METHODS All patients with stage I NSCLC resected at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. RESULTS Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge resection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. CONCLUSION Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors for recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87%; those with three factors are graded Ib, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.
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Origoni, Massimo, Francesco Cantatore, Giorgio Candotti y Massimo Candiani. "Prognostic Significance of Neutrophil/Lymphocytes Ratio (NLR) in Predicting Recurrence of Cervical Dysplasia". BioMed Research International 2022 (11 de abril de 2022): 1–7. http://dx.doi.org/10.1155/2022/1149789.
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Objective. The objective of the present study was to investigate the potential prognostic role of neutrophil-lymphocyte ratio (NLR) in comparison with known parameters of prediction for the detection of recurrences of cervical intraepithelial neoplasia (CIN) after treatment. Methods. We retrospectively evaluated patients who underwent surgical treatment for CIN2, CIN3, and carcinoma in situ (CIN2+) between 2010 and 2019. NLR was recorded before surgery, and the follow-up records of patients were analyzed. Cases were splitted into two subgroups according to baseline NLR—low-NLR for <2 and high-NLR for ≥2 values of the index—and correlated with recurrences. Results. 428 cases fulfilled the criteria and were included in the study. Recurrence rate in patients with NLR <2.0 and NLR ≥2.0 was 15.2% and 27.3%, respectively, being the odd ratio for recurrence significantly higher in patients with NLR ≥2 ( OR = 2.09 ; 95% CI 1.28-3.41; p = 0.003 ). A highly significant statistical difference in recurrence rate was demonstrated, in both univariate and multivariate, for surgical margins, follow-up HPV-DNA status, and NLR values. Conclusion. Preoperative NLR categorization is a strong independent prognostic factor for recurrences after surgical excision of CIN. NLR evaluation is a simple, reproducible, and cost-effective clinical instrument that could optimally be introduced in clinical practice in every setting.
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Cohen, Stuart H., Thomas J. Louie, Matthew Sims, John Pullman, Elaine E. Wang, Elaine E. Wang, Henry Wu, Barbara McGovern, Kelly Brady y Lisa von Moltke. "634. Investigational Microbiome Therapeutic SER-109 Reduces Recurrence of Clostridioides difficile Infection (CDI) Compared to Placebo, Regardless of Risk Factors for Recurrence". Open Forum Infectious Diseases 8, Supplement_1 (1 de noviembre de 2021): S420. http://dx.doi.org/10.1093/ofid/ofab466.832.
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Abstract Background Several demographic and clinical characteristics, including age, sex, medication use and presence of comorbid conditions are considered risk factors for recurrent CDI (rCDI). We examined the efficacy of an investigational purified oral microbiome therapeutic, SER-109, versus placebo in an exploratory analysis of subgroups of patients with risk factors for recurrence who enrolled in ECOSPOR III, a double-blind, placebo controlled trial. Forest Plot of Relative Risks for Recurrence at Week 8 for Selected Baseline Characteristics in the ITT population Methods Patients with ≥ 3 CDI episodes were treated with SER-109 or placebo (four capsules daily for three days) following standard treatment of CDI. The primary efficacy objective was to demonstrate superiority of SER-109 versus placebo in reducing rCDI up to 8 weeks after treatment. In this exploratory analysis, we analyzed the rate of CDI recurrence among SER-109 treated subjects compared to placebo in subgroups defined by rCDI baseline risk factors: proton-pump inhibitor use, number of CDI recurrences, prior FMT history, presence of comorbid conditions and exposure to non-CDI antibiotics after dosing. We also analyzed the rate of CDI recurrence among SER-109 treated subjects by age (≥ 65 and ≤ 65) and gender, which were pre-specified. Results Of 281 patients screened,182 were enrolled. Overall recurrence rates were lower in SER-109 treated patients compared to placebo (12.4% vs 39.8%, respectively); relative risk (RR), 0.32 [95% CI, 0.18-0.58; P< 0.001 for RR< 1.0:P< 0.001 for RR< 0.833]. Co-morbidities including diabetes, renal disease, malignancy, cardiac disease, COPD/asthma, colitis, or immunocompromised status were observed in most patients in the overall study population; 33.5%, 32.4% and 34.1% had 0, 1, or ≥ 2 comorbidities. SER-109 was consistently observed to show greater benefit than placebo in reducing CDI recurrence in all subgroups regardless of the presence or absence of the rCDI risk factor (Fig 1). Conclusion Regardless of risk factor status, SER-109 reduced recurrence of CDI compared to placebo. Most subjects in ECOSPOR III had co-morbidities consistent with the broad inclusion criteria in this Phase 3 trial. Despite a high proportion of patients with co-morbidities in ECOSPOR III, SER-109 significantly reduced the risk of recurrence compared to placebo. Disclosures Stuart H. Cohen, MD, Seres (Research Grant or Support) Thomas J. Louie, MD, Artugen (Advisor or Review Panel member)Crestone (Consultant, Grant/Research Support)Da Volterra (Advisor or Review Panel member)Finch Therapeutics (Grant/Research Support, Advisor or Review Panel member)MGB Biopharma (Grant/Research Support, Advisor or Review Panel member)Rebiotix (Consultant, Grant/Research Support)Seres Therapeutics (Consultant, Grant/Research Support)Summit PLC (Grant/Research Support)Vedanta (Grant/Research Support, Advisor or Review Panel member) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Kelly Brady, MS, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)
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SHARMA, MUKUT, RAM SHARMA, ELLEN T. MCCARTHY y VIRGINIA J. SAVIN. "“The FSGS Factor”". Journal of the American Society of Nephrology 10, n.º 3 (marzo de 1999): 552–61. http://dx.doi.org/10.1681/asn.v103552.
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Abstract. A circulating causative factor has been postulated in focal segmental glomerulosclerosis (FSGS). It has been shown that serum or plasma from some FSGS increases glomerular albumin permeability (Palb) in vitro. Palb greater than 0.5 (i.e., FS activity) is associated with recurrence after transplantation. Specimens from 15 FSGS patients were studied to document the presence of a permeability factor, to isolate this factor, to characterize its biochemical properties, and to show its effect in vivo. Total lipids were extracted by chloroform/methanol (2:1); FS activity was absent from total lipid extract. Chylomicrons and lipoproteins were removed from the plasma with dextran sulfate, followed by sequential precipitation of proteins at 50 and 70% ammonium sulfate saturation. FS activity was retained in the 70% ammonium sulfate supernatant and exhibited a 100-fold purification. FS activity was lost after heating at 100°C for 10 min or after protease digestion. Under nondenaturing conditions, electrophoresis of the FSGS 70% supernatant showed a prominent low molecular weight band that was not evident in the 70% supernatant from normal plasma. Dialysis and centrifugation-based membrane ultrafiltration of the FSGS factor indicated a molecular size between 30 and 50 kD. Injection of the 70% FSGS supernatant into rats caused a threefold increase in urine protein in collections from 6 to 24 h after injection. No increase in proteinuria occurred in rats injected with 70% supernatant from normal individuals. It is concluded that the FSGS factor is a low molecular weight protein with the potential to increase Palb in vitro and to cause proteinuria in vivo.
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Weber, Catherine, Nelly G. Adel, Elyn Riedel y Gerald A. Soff. "Identification and Characterization of Recurrent Venous Thrombosis In Cancer Patients". Blood 116, n.º 21 (19 de noviembre de 2010): 3328. http://dx.doi.org/10.1182/blood.v116.21.3328.3328.
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Abstract Abstract 3328 Background: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Standard of care for treatment is Low Molecular Weight Heparin, but recurrence of VTE remains a concern. We performed a retrospective analysis of our institutional experience, to characterize the patients who had a recurrence of VTE while on therapeutic doses of Dalteparin. Objectives: 1. To determine the VTE recurrence rate for cancer patients on therapeutic Dalteparin. 2. To elucidate potential risk factors for recurrence. 3. To determine the impact of recurrent VTE on overall survival. Methods: Patients beginning treatment for VTE with dalteparin between 1/1/2008 and 12/10/ 2009 were retrospectively identified through the hospital's electronic medical records system and cases of recurrent VTE were characterized. Overall survival was estimated using the Kaplan-Meier method and the influence of VTE recurrence on overall survival was analyzed as a time-dependent covariate using a Cox proportional hazards model. Results: 1,392 patients, treated for VTE with dalteparin were included in this study. 34 recurrent VTE episodes were identified. The overall incidence of recurrent thrombosis by six months was 2.3% (95% CI: 1.7%-3.3%). Older age was significantly associated with recurrence (p=0.04). Lung cancer patients had a significantly elevated risk of recurrence (5.6%, p=0.03). No other cancer types were associated with a significant trend to increased recurrent VTE rates. The incidence of recurrent VTE was higher among females compared to males (3.0% vs. 1.6%), although this trend was not statistically significant (P = 0.08). After adjusting for gender, sex and cancer diagnosis, developing a recurrent VTE was associated with a 3.0-fold hazard ratio of death (<0.0001). Conclusions: The rate of recurrent VTE in cancer patients at MSKCC is low in comparison with previously published reports. However, we identified both older age and lung cancer diagnosis as statistically significant risk factors for recurrent VTE. Females also experienced a higher rate of recurrent thrombosis when compared to males, although this result was not statistically significant. The hazard ratio for death was three times that for a patient with recurrent thrombosis when compared to one without subsequent VTE, suggesting recurrence of VTE remains an important influence on cancer-associated mortality. Disclosures: No relevant conflicts of interest to declare.
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Wacharachawana, Sornsittipong, Paweena Phaliwong, Sinart Prommas, Buppa Smanchat, Kornkarn Bhamarapravatana y Komsun Suwannarurk. "Recurrence Rate and Risk Factors for the Recurrence of Ovarian Endometriosis after Laparoscopic Ovarian Cystectomy". BioMed Research International 2021 (25 de enero de 2021): 1–5. http://dx.doi.org/10.1155/2021/6679641.
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The aim of this study was to identify the recurrence rate and risk factors for the recurrence of ovarian endometriosis (OE) after laparoscopic cystectomy. This was a retrospective cross-sectional study. Subjects were OE cases who underwent laparoscopic ovarian cystectomy at Bhumibol Adulyadej Hospital (BAH). The period of this study was from January 2008 to December 2017. Ovarian histopathology and at least one-year follow-up after surgery were the prerequisite requirements. A total of 106 OE cases were included in the study. Subjects were classified into recurrence and nonrecurrence groups. It comprised of 24 and 82 cases, respectively. The mean age of the participant was 32.4 years old. The demographic characters of both groups were comparable. The recurrence rate after laparoscopic OE surgery in the present study was 22.6% (24/106). The average largest diameter of OE in the present study was 54.5 mm. Postoperative medical treatment (OR 3.15, 95% CI 1.14-8.74, p = 0.02 ) and postoperative pregnancy (OR 2.86, 95% CI 1.03-7.93, p = 0.04 ) were associated factors for recurrence decrement. The recurrence rate of OE after laparoscopic cystectomy was 22.6%. Postoperative medical treatment and postoperative pregnancy were a significant factor that lowered OE recurrence.
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Fujiwara, Y., K. Kiura, S. Toyooka, K. Hotta, M. Tabata, N. Takigawa, T. Kozuki, K. Ohashi, K. Matsuo y M. Tanimoto. "Never-smoking history predicts long-term survival in patients with non-small cell lung cancer with postoperative recurrence". Journal of Clinical Oncology 24, n.º 18_suppl (20 de junio de 2006): 20047. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.20047.
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20047 Background: Factors affecting long-term survival after postoperative recurrence in non-small cell lung cancer (NSCLC) patients have not been fully understood. Furthermore, molecular features of them also have remained undetermined. The aim of this study was to identify these possible factors and to investigate their association with epidermal growth factor receptor (EGFR) mutation. Methods: Fifty-eight patients with postoperative recurrent NSCLC treated at Okayama University Hospital between January 1999 and December 2003 were retrospectively analyzed. We defined those surviving for 2 years or longer after postoperative recurrence as long-term survivors. Tumor samples for EGFR mutation analysis were available in 32 (55%) patients and were examined in exons 18 to 21 of EGFR using direct sequence method. Results: Demographics of 58 patients were as follows: median age 65 years (range, 33–85 years), male/female, 69%/31%; adenocarcinoma/others, 69%/31%; ever/never-smokers, 66%/34% and local/local and distant/distant recurrence; 29%/10%/61%. Median survival time and 1-year survival rate for 58 patients were 22.7 months and 79%, respectively, with a minimum follow-up time of 2 years. Half of 28 long-term survivors did not have any smoking history, whereas only 6 never-smokers were included in the remaining 30 patients who died within 2 years, indicating that never-smoking history is significantly associated with long-term survival (p=0.016). In multivariate analysis, never-smoking history was a significant predictive factor for long-term survival (Odds ratio 4.90, 95% confidence interval: 1.26–19.00, p=0.022). Among 32 patients analyzed for EGFR mutation, patients harboring EGFR mutation in ever-smokers and in never-smokers were 10% and 82%, respectively. Seven (47%) of 15 long-term survivors analyzed had EGFR mutation; however, only 4 (24%) of 17 patients who died within 2 years did (p = 0.169). Conclusions: Our data suggest that never-smoking history might have a favorable effect on long-term survival in postoperative recurrent NSCLC patients, and long-term survivors tend to have EGFR mutation. No significant financial relationships to disclose.
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Rajesh, Yetirajam y Devanand Sarkar. "Molecular Mechanisms Regulating Obesity-Associated Hepatocellular Carcinoma". Cancers 12, n.º 5 (20 de mayo de 2020): 1290. http://dx.doi.org/10.3390/cancers12051290.
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Obesity is a global, intractable issue, altering inflammatory and stress response pathways, and promoting tissue adiposity and tumorigenesis. Visceral fat accumulation is correlated with primary tumor recurrence, poor prognosis and chemotherapeutic resistance. Accumulating evidence highlights a close association between obesity and an increased incidence of hepatocellular carcinoma (HCC). Obesity drives HCC, and obesity-associated tumorigenesis develops via nonalcoholic fatty liver (NAFL), progressing to nonalcoholic steatohepatitis (NASH) and ultimately to HCC. The better molecular elucidation and proteogenomic characterization of obesity-associated HCC might eventually open up potential therapeutic avenues. The mechanisms relating obesity and HCC are correlated with adipose tissue remodeling, alteration in the gut microbiome, genetic factors, ER stress, oxidative stress and epigenetic changes. During obesity-related hepatocarcinogenesis, adipokine secretion is dysregulated and the nuclear factor erythroid 2 related factor 1 (Nrf-1), nuclear factor kappa B (NF-κB), mammalian target of rapamycin (mTOR), phosphatidylinositol-3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/Akt, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways are activated. This review captures the present trends allied with the molecular mechanisms involved in obesity-associated hepatic tumorigenesis, showcasing next generation molecular therapeutic strategies and their mechanisms for the successful treatment of HCC.
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Gnimavo, Ronald, Alban Besnard, Horace Degnonvi, Juliana Pipoli Da Fonseca, Marie Kempf, Christian Roch Johnson, Alexandra Boccarossa, Yao Télesphore Brou, Laurent Marsollier y Estelle Marion. "Molecular and epidemiological characterization of recurrent Mycobacterium ulcerans infections in Benin". PLOS Neglected Tropical Diseases 15, n.º 12 (28 de diciembre de 2021): e0010053. http://dx.doi.org/10.1371/journal.pntd.0010053.
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Background Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans, an environmental mycobacterium. Although transmission of M. ulcerans remains poorly understood, the main identified risk factor for acquiring Buruli ulcer is living in proximity of potentially contaminated water sources. Knowledge about the clinical features of Buruli ulcer and its physiopathology is increasing, but little is known about recurrence due to reinfection. Methodology/Principal findings We describe two patients with Buruli ulcer recurrence due to reinfection with M. ulcerans, as demonstrated by comparisons of DNA from the strains isolated at the time of the first diagnosis and at recurrence. Based on the spatial distribution of M. ulcerans genotypes in this region and a detailed study of the behavior of these two patients with respect to sources of water as well as water bodies and streams, we formulated hypotheses concerning the sites at which they may have been contaminated. Conclusions/Significance Second episodes of Buruli ulcer may occur through reinfection, relapse or a paradoxical reaction. We formally demonstrated that the recurrence in these two patients was due to reinfection. Based on the sites at which the patients reported engaging in activities relating to water, we were able to identify possible sites of contamination. Our findings indicate that the non-random distribution of M. ulcerans genotypes in this region may provide useful information about activities at risk.
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Smith, Benjamin D., Bruce G. Haffty y Clarence T. Sasaki. "Molecular Markers in Head and Neck Squamous Cell Carcinoma: Their Biological Function and Prognostic Significance". Annals of Otology, Rhinology & Laryngology 110, n.º 3 (marzo de 2001): 221–28. http://dx.doi.org/10.1177/000348940111000304.
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Head and neck squamous cell carcinoma affects more than 500,000 people worldwide each year. Despite optimal treatment with surgery, irradiation, and chemotherapy, disease recurrence and progression remains a common and challenging oncological problem. Recently, interest has developed in identifying novel molecular markers that allow identification of those patients at increased risk for locoregional recurrence and death. This article reviews several such molecular markers studied in head and neck cancer, including p53, angiogenesis-related markers, cyclin D1, and epidermal growth factor receptor. The biological function of these markers and the potential clinical implications are discussed. The purpose of this review is to update the otolaryngologist on a rapidly emerging segment of applied translational research in our field.
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Barbar, Ruba, Hana Hakim, Randall Hayden y Randall Hayden. "2383. Epidemiological and Clinical Features of Clostridioides difficile Infections in Pediatric Oncology and Transplant Patients". Open Forum Infectious Diseases 6, Supplement_2 (octubre de 2019): S822—S823. http://dx.doi.org/10.1093/ofid/ofz360.2061.
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Abstract Background Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated diarrhea-causing significant morbidity and mortality in adults. The epidemiology and clinical course of CDI in children, especially with cancer are poorly defined. We aim to describe the clinical, epidemiological features and outcomes of CDI, and identify risk factors for recurrence in a pediatric oncology center Methods This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by electronic medical record search for positive C. difficile PCR tests. CDI episodes were classified as incident, duplicate or recurrent and community-onset (CO), hospital-onset (HO), or community-onset healthcare facility associated (COHCFA) using National Healthcare Safety Network surveillance definitions. Demographics, underlying diagnosis, CDI characteristics, drug exposure, and outcomes were analyzed. Risk factors for CDI recurrence were assessed by logistic regression. Results One hundred-eighty patients developed 305 CDI episodes; 233 (78%) were incident, 65 (22%) recurrent, and 7 duplicate and removed from the analysis. Recurrence occurred after 51 incident episodes (Table 1). Median age (range) was 5.7 (0.5–25.5) years. Underlying diagnoses were leukemia/lymphoma (56%) and solid/brain tumors (42%). 87 (29%) received HSCT. Almost all patients received antibiotics 4 weeks prior to CDI. 14% received laxatives 72 hours prior to CDI. 50% of patients were neutropenic. The median (range) duration of diarrhea was 10.0 (1–77). Thirty patients (15%) were hospitalized due to CDI, for a median (range) of 3 (1–49) days. 16% had a delay in chemotherapy due to CDI. There was no ICU admissions nor death due to CDI. None of the evaluated variables was identified as a significant risk factor for CDI recurrence by logistic regression (Table 3). Conclusion CDI in pediatric oncology and transplant patients ran a generally mild course, associated with chemotherapy delay and hospitalization in a small fraction, and no attributable ICU admission nor death. CDI recurred in less than a quarter of patients. Risk factors for CDI recurrence were not identified. Disclosures Randall Hayden, MD, Abbott Molecular: Advisory Board; Quidel: Advisory Board; Roche Diagnostics: Advisory Board
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Yang, Cheng-Hong, Sin-Hua Moi, Li-Yeh Chuang, Shyng-Shiou F. Yuan, Ming-Feng Hou, Yi-Chen Lee y Hsueh-Wei Chang. "Interaction of MRE11 and Clinicopathologic Characteristics in Recurrence of Breast Cancer: Individual and Cumulated Receiver Operating Characteristic Analyses". BioMed Research International 2017 (2017): 1–9. http://dx.doi.org/10.1155/2017/2563910.
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The interaction between the meiotic recombination 11 homolog A (MRE11) oncoprotein and breast cancer recurrence status remains unclear. The aim of this study was to assess the interaction between MRE11 and clinicopathologic variables in breast cancer. A dataset for 254 subjects with breast cancer (220 nonrecurrent and 34 recurrent) was used in individual and cumulated receiver operating characteristic (ROC) analyses of MRE11 and 12 clinicopathologic variables for predicting breast cancer recurrence. In individual ROC analysis, the area under curve (AUC) for each predictor of breast cancer recurrence was smaller than 0.7. In cumulated ROC analysis, however, the AUC value for each predictor improved. Ten relevant variables in breast cancer recurrence were used to find the optimal prognostic indicators. The presence of any six of the following ten variables had a high (79%) sensitivity and a high (70%) specificity for predicting breast cancer recurrence: tumor size ≥ 2.4 cm, tumor stage II/III, therapy other than hormone therapy, age ≥ 52 years, MRE11 positive cells > 50%, body mass index ≥ 24, lymph node metastasis, positivity for progesterone receptor, positivity for epidermal growth factor receptor, and negativity for estrogen receptor. In conclusion, this study revealed that these 10 clinicopathologic variables are the minimum discriminators needed for optimal discriminant effectiveness in predicting breast cancer recurrence.
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Roh, Yun-Gil, Jeong-Yeon Mun, Seon-Kyu Kim, Won Young Park, Mi-So Jeong, Tae Nam Kim, Won-Tae Kim, Yung Hyun Choi, In-Sun Chu y Sun-Hee Leem. "Fanconi Anemia Pathway Activation by FOXM1 is Critical to Bladder Cancer Recurrence and Anticancer Drug Resistance". Cancers 12, n.º 6 (30 de mayo de 2020): 1417. http://dx.doi.org/10.3390/cancers12061417.
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Although the 5-year survival rate of patients diagnosed with nonmuscle invasive bladder cancer (NMIBC) has reached 85%, more than 50% of patients suffer from frequent recurrences. To identify molecular targets associated with recurrence of NMIBC, we analyzed gene expression data and found that FOXM1 and FANCD2 were involved in recurrence. Therefore, we investigated how these genes were involved in the mechanism of recurrence and confirmed their usefulness as biomarkers. Investigation have shown that FOXM1 directly regulated the transcription of FANCD2, which is the key gene of the Fanconi anemia (FA) pathway. Depletion of FOXM1 resulted in DNA repair defects in the FA pathway and in decreased resistance to chemotherapy. Thus, the FANCD2-associated FA pathway activated by FOXM1 is an important mechanism involved in chemotherapy-related recurrence. In conclusion, FOXM1 and FANCD2 can be used as prognostic factors that are associated with high risk of recurrence and with anticancer drug resistance properties in NMIBC patients.
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de Brot, Simone, Atara Ntekim, Ryan Cardenas, Victoria James, Cinzia Allegrucci, David M. Heery, David O. Bates, Niels Ødum, Jenny L. Persson y Nigel P. Mongan. "Regulation of vascular endothelial growth factor in prostate cancer". Endocrine-Related Cancer 22, n.º 3 (13 de abril de 2015): R107—R123. http://dx.doi.org/10.1530/erc-15-0123.
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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to ∼30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically ≤24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.
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Pinyol, Roser, Robert Montal, Laia Bassaganyas, Daniela Sia, Tadatoshi Takayama, Gar-Yang Chau, Vincenzo Mazzaferro et al. "Molecular predictors of prevention of recurrence in HCC with sorafenib as adjuvant treatment and prognostic factors in the phase 3 STORM trial". Gut 68, n.º 6 (2 de octubre de 2018): 1065–75. http://dx.doi.org/10.1136/gutjnl-2018-316408.
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ObjectiveSorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence-free survival (RFS). The biomarker companion study BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib and (B) prognostic factors with B level of evidence.DesignTumour tissue from 188 patients randomised to receive sorafenib (83) or placebo (105) in the STORM trial was collected. Analyses included gene expression profiling, targeted exome sequencing (19 known oncodrivers), immunohistochemistry (pERK, pVEGFR2, Ki67), fluorescence in situ hybridisation (VEGFA) and immunome. A gene signature capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS events were recurrences, thus time to recurrence equalled RFS. Predictive and prognostic value was assessed using Cox regression models and interaction test.ResultsBIOSTORM recapitulates clinicopathological characteristics of STORM. None of the biomarkers tested (related to angiogenesis and proliferation) or previously proposed gene signatures, or mutations predicted sorafenib benefit or recurrence. A newly generated 146-gene signature identifying 30% of patients captured benefit to sorafenib in terms of RFS (p of interaction=0.04). Thesesorafenib RFS responderswere significantly enriched in CD4+T, B and cytolytic natural killer cells, and lacked activated adaptive immune components. Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017) were independent prognostic factors.ConclusionIn BIOSTORM, only hepatocytic pERK and microvascular invasion predicted poor RFS. No mutation, gene amplification or previously proposed gene signatures predicted sorafenib benefit. A newly generated multigene signature associated with improved RFS on sorafenib warrants further validation.Trial registration numberNCT00692770.
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Zhou, Haiying, Zuhua Sun, Meng Zhao, Xiaoling Liu, Xuan Jiao, Weiwei Zheng y Feng Zhang. "Prognostic Factor Study of Macular Edema Recurrence in Retinal Vein Occlusion after Conbercept Treatment: A Post Hoc Analysis of the FALCON Study". Computational and Mathematical Methods in Medicine 2022 (29 de julio de 2022): 1–9. http://dx.doi.org/10.1155/2022/3616044.
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Objective. The study was aimed at exploring the potential predictive factors associated with the recurrence of macular edema (ME) secondary to vein occlusion (RVO) after intravitreal antivascular endothelial growth factor (VEGF) loading treatment in the FALCON study. Methods. This is a post hoc analysis of 30 patients with central RVO and 30 patients with branch RVO. All patients received a monthly administration of intravitreal conbercept during the 3-month loading phase and pro re nata (PRN) treatment during the 6-month follow-up period. Based on the recurrence of ME at the first follow-up visit, patients were classified into the recurrence group or nonrecurrence group. The primary endpoint was to explore the risk factors for recurrence among baseline characteristics, fluorescein angiography (FA) patterns, and optical coherence tomography (OCT). Results. In general, 38 patients (64.4%) experienced ME recurrence at the first follow-up visit (3 months), regardless of disease type ( p = 0.32 ). Significant improvements in VA were noted in both the nonrecurrence and recurrence groups ( p < 0.001 ), however, without significant between-group differences ( p = 0.1 ). A significant reduction in CRT in both groups ( p < 0.001 ) was identified, and patients without recurrence showed a greater reduction in CRT compared with those with recurrence ( p < 0.001 ). In addition, logistic regression analyses indicated the corrections of ME recurrence with baseline macular volume and the disruption of the outer limiting membrane at the fovea. Conclusion. This study suggested that OCT parameters, including baseline macular volume and outer limiting membrane disruption, and reduction in CRT after loading therapy were more predictive of ME recurrence than FA patterns or visual changes following conbercept loading therapy.
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Klironomos, G., A. Mansouri, A. Kilian, L. Gonen, O. Khan y G. Zadeh. "Perioperative predictive factors of intracranial meningioma recurrence following surgical resection". Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 42, S1 (mayo de 2015): S46. http://dx.doi.org/10.1017/cjn.2015.206.
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Background: Meningiomas represent the commonest benign intracranial tumor and surgical resection is the first line treatment. Tumor recurrence after surgical resection is common. The aim of this study is to identify peri-operative predictors of meningioma recurrence following surgical resection Methods: This was a retrospective hospital-based study of all surgical cases between January 1990 and June 2014. Information regarding age, gender, peri-operative imaging parameters such as peri-tumoral edema or post-operative hemorrhage or residual, and grade were collected. Linear and volumetric measurements (of both tumor volume and volume of edema) were collected as well. Results: Overall, 464 patients were reviewed; n=154(34%) percent of patients were male. The grade distribution was: 296 (74.6%) were Grade I, 78 (19.6%) Grade II, and 23 (5.8%) Grade III. Post-operative tumor bed hemorrhage, noted in 119 (29.9%) of cases, and preoperative peri-tumoral edema volume were significant predictors of tumor recurrence following resection (P= 0.002 and 0.037, respectively). These parameters did not correlate with the MIB-1 index, tumour residual, grade of the tumour, or primary versus recurrent presentation. Conclusions: Pre-operative peri-tumoral edema and post-operative tumor bed hemorrhage are independent predictive of tumor recurrence. Identification of other molecular and/or radiological predictive of recurrence factors could add in our understanding of meningioma behavior.
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Chiu, Harold Henrison, Dianne Grace Corpuz, Angelo Dela Tonga, Ma Jowina Galarion, Michele Hernandez-Diwa, Anna Angelica Macalalad-Josue, Patricia Maningat, Sahra May Paragas y Oliver Pintor. "PSAT374 Prognostic Utility of BRAF V600E Mutation as a Risk Factor for Tumor Recurrence among Filipino Patients with Papillary Thyroid Cancer". Journal of the Endocrine Society 6, Supplement_1 (1 de noviembre de 2022): A885. http://dx.doi.org/10.1210/jendso/bvac150.1832.
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Abstract Background Epidemiological studies have shown that Filipinos have a higher prevalence of well-differentiated thyroid cancer and a higher rate of recurrence amongst the different ethnicities. The BRAF V600E mutation has long been proposed as a potential prognostic marker in aggressive papillary thyroid cancers. In this study, we determined whether BRAF V600E mutation can be a novel risk factor for tumor recurrence in papillary thyroid cancer. Methodology We conducted an age and sex-matched case-control study of 14 patients for each arm using the histopathologic diagnosis of papillary thyroid cancer and with an available paraffin block as sample source. Pertinent demographic, clinical and histopathologic data were collected. The BRAF V600E mutation was detected using polymerase chain reaction following DNA extraction from the paraffin-embedded tissue blocks. Multivariate logistic regression was performed to determine the association between presence of BRAF V600E mutation with tumor recurrence at 95% confidence interval. Results The BRAF V600E mutation prevalence was at 32.14% (95% CI: 15.88-52.35%) for all cases; 21.43% (95% CI: 4.66-50.80%) among those with recurrence and 42.86% (95% CI: 17.66-71.14%) among those without recurrence. There was insufficient evidence to prove a significant association between BRAF V600E mutation and recurrence, OR 0.50 (95% CI: 0.08-2.34, p = 0.327). Conclusion Our study showed that there was a trend towards no association between BRAF V600E mutation and recurrence. However, due to the small sample size, we cannot accurately establish an association between the presence of the BRAF V600E mutation and increased recurrence rates among Filipinos diagnosed with papillary thyroid cancer. Despite the dismal results, we still opted to present the results of our study as there were many challenges encountered in the molecular diagnosis of thyroid cancer in developing countries like the Philippines. This opens the many possibilities for future studies and collaborations amongst different institutions to firmly establish the role of BRAF V600E in Filipinos with papillary thyroid cancer tumor recurrence. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
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Behling, Felix, Johann-Martin Hempel y Jens Schittenhelm. "Brain Invasion in Meningioma—A Prognostic Potential Worth Exploring". Cancers 13, n.º 13 (29 de junio de 2021): 3259. http://dx.doi.org/10.3390/cancers13133259.
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Most meningiomas are slow growing tumors arising from the arachnoid cap cells and can be cured by surgical resection or radiation therapy in selected cases. However, recurrent and aggressive cases are also quite common and challenging to treat due to no established treatment alternatives. Assessment of the risk of recurrence is therefore of utmost importance and several prognostic clinical and molecular markers have been established. Additionally, the identification of invasive growth of meningioma cells into CNS tissue was demonstrated to lead to a higher risk of recurrence and was therefore integrated into the WHO classification of CNS tumors. However, the evidence for its prognostic impact has been questioned in subsequent studies and its exclusion from the next WHO classification proposed. We were recently able to show the prognostic impact of CNS invasion in a large comprehensive retrospective meningioma cohort including other established prognostic factors. In this review we discuss the growing experiences that have been gained on this matter, with a focus on the currently nonuniform histopathological assessment, imaging characteristics and intraoperative sampling as well as the overall outlook on the future role of this potential prognostic factor.
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Vernon, Katherine A., Daniel P. Gale, Elena Goicoechea de Jorge, Adam G. McLean, Patrick H. Maxwell, Matthew C. Pickering y H. Terence Cook. "Recurrence of complement factor H-related protein 5 nephropathy in a renal transplant". Molecular Immunology 47, n.º 13 (agosto de 2010): 2202. http://dx.doi.org/10.1016/j.molimm.2010.05.024.
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Infante, Barbara, Michele Rossini, Serena Leo, Dario Troise, Giuseppe Stefano Netti, Elena Ranieri, Loreto Gesualdo, Giuseppe Castellano y Giovanni Stallone. "Recurrent Glomerulonephritis after Renal Transplantation: The Clinical Problem". International Journal of Molecular Sciences 21, n.º 17 (19 de agosto de 2020): 5954. http://dx.doi.org/10.3390/ijms21175954.
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Glomerulonephritis (GN) continues to be one of the main causes of end-stage kidney disease (ESKD) with an incidence rating from 10.5% to 38.2%. Therefore, recurrent GN, previously considered to be a minor contributor to graft loss, is the third most common cause of graft failure 10 years after renal transplantation. However, the incidence, pathogenesis, and natural course of recurrences are still not completely understood. This review focuses on the most frequent diseases that recur after renal transplantation, analyzing rate of recurrence, epidemiology and risk factors, pathogenesis and bimolecular mechanisms, clinical presentation, diagnosis, and therapy, taking into consideration the limited data available in the literature. First of all, the risk for recurrence depends on the type of glomerulonephritis. For example, recipient patients with anti-glomerular basement membrane (GBM) disease present recurrence rarely, but often exhibit rapid graft loss. On the other hand, recipient patients with C3 glomerulonephritis present recurrence in more than 50% of cases, although the disease is generally slowly progressive. It should not be forgotten that every condition that can lead to chronic graft dysfunction should be considered in the differential diagnosis of recurrence. Therefore, a complete workup of renal biopsy, including light, immunofluorescence and electron microscopy study, is essential to provide the diagnosis, excluding alternative diagnosis that may require different treatment. We will examine in detail the biomolecular mechanisms of both native and transplanted kidney diseases, monitoring the risk of recurrence and optimizing the available treatment options.
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Varn, Frederick, Gordon Ye, Padmaja Ghospurkar, Taylor Wade, Mustafa Khasraw, Eric S. Lipp, Beth Hermes et al. "PATH-11. THE LONGITUDINAL EVOLUTIONARY TRAJECTORY OF OLIGODENDROGLIOMA IS DRIVEN BY TREATMENT-ASSOCIATED GENETIC ALTERATIONS". Neuro-Oncology 24, Supplement_7 (1 de noviembre de 2022): vii152. http://dx.doi.org/10.1093/neuonc/noac209.584.
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Abstract Oligodendroglioma is a subtype of diffuse glioma defined by a mutation in the isocitrate dehydrogenase (IDH) genes and a co-deletion of chromosome arms 1p and 19q. These tumors primarily occur in adult patients in their third and fourth decade of life and are universally fatal due to an inevitable recurrence that follows a treatment regimen of surgical resection and an optional combination of alkylating chemotherapy and/or radiation therapy. While initially slow growing, recurrent tumors exhibit increasingly aggressive phenotypes that become progressively more difficult to treat with conventional therapy. Currently, the molecular mechanisms and cellular phenotypes that drive this recurrence remain unknown. To understand these factors, we assembled a cohort of matched initial and recurrent oligodendroglioma samples from over 100 patients and performed whole-genome sequencing and whole-exome sequencing on each of them. To link these molecular profiles to cell state changes, we additionally performed bulk and single-nucleus RNA-sequencing on a subset of these tumor pairs. In nearly 40% of alkylating chemotherapy-treated patients, recurrent tumors presented with hypermutation that corresponded with an increase in neoplastic cell proliferation. Additionally, while individual somatic alterations specific to recurrence were relatively rare, we observed a subset of tumors that acquired deletions in the cell cycle regulator CDKN2A following treatment with radiotherapy. Acquisition of either of these features associated with shorter patient survival and higher grade at recurrence, implicating cell cycle dysregulation as a mechanism of treatment resistance and increased tumor severity. Together, these results indicate that oligodendrogliomas evolve in a treatment-specific manner following chemo- and radiation therapy and highlight key pathways that can be targeted to delay the onset of recurrence.
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Chen, Lin, Xiaodong Shi, Guoyue Lv, Xiaodong Sun, Chao Sun, Yanjun Cai, Junqi Niu, Jinglan Jin, Ning Liu y Wanyu Li. "The long-term outcomes of deceased-donor liver transplantation for primary biliary cirrhosis: a two-center study in China". PeerJ 8 (19 de agosto de 2020): e9563. http://dx.doi.org/10.7717/peerj.9563.
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Background & Aims Factors that influence the outcomes after deceased-donor liver transplantation (DDLT) for primary biliary cirrhosis (PBC) are not well known. We aimed to clarify these effects on the outcomes after DDLT. Methods We retrospectively analyzed patients with PBC who underwent DDLT from March 2006 to July 2018 at the organ transplantation center of the First Hospital of Jilin University and the First Central Hospital of Tianjin. Changes in liver function were assessed posttransplantation. Recurrence, survival rate, and complications were recorded at follow-up. The effect of liver transplantation on survival and recurrence was evaluated using univariate and/or multivariate Cox regression analyses. Results In total, 69 patients with PBC undergoing DDLT were included in this study. At 4 weeks posttransplant, all liver function tests were normal. During a median follow-up time of 32 months, 5-year overall survival and recurrence rates were estimated as 95.1% and 21.8%, respectively. A recipient aspartate aminotransferase-to-platelet ratio index (APRI) greater than 2 was negatively associated with survival (P = 0.0018). Multivariate regression analysis demonstrated that age younger than 48 years was an independent risk factor for recurrent PBC in recipients undergoing liver transplantation (hazard ratio 0.028, 95% confidence interval 0.01–0.71, P = 0.03). Posttransplant infections (62%) and biliary tract complications (26%) were the most common complications. Conclusion Liver transplantation is an effective treatment for patients with PBC. Liver function normalizes by 4 weeks posttransplant. Although posttransplant survival rate is high, recurrence is possible. To some extent, survival rate and recurrence rate can be predicted by APRI and age, respectively.