scholarly journals Segmental Histological Normalisation Occurs in Ulcerative Colitis but Does Not Improve Clinical Outcomes

2020 ◽  
Vol 14 (10) ◽  
pp. 1345-1353 ◽  
Author(s):  
Britt Christensen ◽  
Stephen B Hanauer ◽  
Peter R Gibson ◽  
Jerrold R Turner ◽  
John Hart ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Outcomes ◽  
Clinical Relapse ◽  
Relapse Free Survival ◽  
Disease Extent ◽  
Free Survival ◽  
Current Smoking ◽  
Younger Age ◽  
Age Of Diagnosis ◽  
Distal Direction

Abstract Background and Aims Complete histological normalisation and reduction of inflammation severity in patients with ulcerative colitis are associated with improved clinical outcomes, but the clinical significance of normalisation of only segments of previously affected bowel is not known. We examined the prevalence, pattern, predictors, and clinical outcomes associated with segmental histological normalisation in in patients with ulcerative colitis. Methods Medical records of patients with confirmed ulcerative colitis and more than one colonoscopy were sought. Segmental histological normalisation was defined as histological normalisation of a bowel segment [rectum, left-sided or right-sided colon] that had previous evidence of chronic histological injury. We assessed the variables influencing these findings and whether segmental normalisation was associated with improved clinical outcomes. Results Of 646 patients, 32% had segmental and 10% complete histological normalisaton when compared with their maximal disease extent. Most [88%] had segmental normalisation in a proximal-to-distal direction. Others had distal-to-proximal or patchy normalisation. On multivariate analysis, only current smoking [p = 0.040] and age of diagnosis ≤16 years [p = 0.028] predicted segmental histological normalisation. Of 310 who were in clinical remission at initial colonoscopy, 77 [25%] experienced clinical relapse after median 1.3 [range 0.06–7.52] years. Only complete histological normalisation of the bowel was associated with improved relapse-free survival (hazard ratio [HR] 0.23; 95% confidence interval [CI] 0.08–0.68; p = 0.008]. Conclusions Segmental histological normalisation occurs in 32% of patients with ulcerative colitis and is increased in those who smoke or were diagnosed at younger age. Unlike complete histological normalisation, segmental normalisation does not signal improved clinical outcomes.

scholarly journals Predictive factors of relapse after dose reduction of oral 5-aminosalicylic acid in patients with ulcerative colitis in the remission phase

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255620
Author(s):  
Akira Madarame ◽  
Masakatsu Fukuzawa ◽  
Yoshiya Yamauchi ◽  
Shin Kono ◽  
Akihiko Sugimoto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ulcerative Colitis ◽  
Dose Reduction ◽  
Clinical Relapse ◽  
Aminosalicylic Acid ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Significant Difference ◽  
History Of

Objectives Useful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC. Methods UC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan–Meier method. Results A total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50–293.2). Based on Kaplan–Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001). Conclusions Dose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC.

592 Histological Normalization Is Associated With Superior Relapse Free Survival Compared to Histological Activity and Histological Quiescence in Ulcerative Colitis

2015 ◽  
Vol 148 (4) ◽  
pp. S-115 ◽  
Author(s):  
Britt Christensen ◽  
Olufemi Kassim ◽  
Jonathan Erlich ◽  
Stephen B. Hanauer ◽  
David T. Rubin
Keyword(s):  
Ulcerative Colitis ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Histological Activity

scholarly journals P270 Ulcerative colitis disease extent and inflammatory burden assessment: DUBLIN and modified Nancy score

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S285-S286
Author(s):  
J C Rocha Silva ◽  
J Rodrigues ◽  
A Rodrigues ◽  
A Silva ◽  
C Fernades ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Score ◽  
Mucosal Inflammation ◽  
Clinical Relapse ◽  
Disease Extent ◽  
Faecal Calprotectin ◽  
Protein Levels ◽  
Mayo Score ◽  
Disease Extension ◽  
Inflammatory Burden

Abstract Background Current endoscopic activity scores for ulcerative colitis (UC) do not take into account the extent of mucosal inflammation. The DUBLIN score (Degree of Ulcerative Colitis Burden of Luminal Inflammation) is a simple bedside clinical score that estimates inflammatory burden using both disease severity and extent, which correlates with objective inflammatory markers and is associated with clinical outcomes. The validated Nancy score is used to evaluate histological activity; nonetheless, it does not take in consideration disease extension. We aimed to evaluate the relation of both Mayo and Dublin scores with disease activity and as predictive factors of clinical relapse. Also, we developed a modified Nancy score in order to assess histologic activity considering disease extension. Methods A retrospective cohort study, which consecutively included all UC patients submitted to colonoscopy with biopsies between 2016 and 2019 in our unit. Mayo and DUBLIN scores were calculated. Modified Nancy score was calculated as a product of Nancy Score and disease extent (E1-E3). Correlation of both endoscopic and histologic scores with biomarkers, relapse (in a 6months) and relapse-free time as performed. Results 107 patients were selected, 52.3% (n = 56) male, mean age = 48.4 ± 13.9 years. Mean Dublin score was 2.65 ± 2.75. Mayo and DUBLIN scores presented good correlation (r = 0.880, p &lt; 0.001). Also Dublin score correlated with modified Nancy score (p &lt; 0.001). Both Dublin score (p = 0.009) and modified Nancy score (p = 0.026) correlated with C-reactive protein levels. Nancy score correlated with faecal calprotectin (p = 0,025). Relapse occurred in 26.2% (n = 28) of patients with a mean time for the event of 13 ± 7 weeks. Mayo Score (p &lt; 0.001), Dublin score (p &lt; 0.001), Nancy score (p &lt; 0.001) and modified Nancy score (p &lt; 0.001) presented a significant association with relapse. Areas under the ROC curve were 0.786 for Dublin score, 0.751 for Mayo score, 0.84 for Nancy score and 0.79 for modified Nancy score. Conclusion DUBLIN and modified Nancy scores correlate with each other and with biomarkers and are independent predictors of relapse. Dublin score was superior to Mayo score in the prediction of relapse.

Nordic Mantle Cell Lymphoma (MCL) Project: Preemptive Rituximab Treatment of Molecular Relapse Following Autotransplant Can Reinduce Molecular Remission and Prolonged Disease-Free Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2429-2429
Author(s):  
Christian H. Geisler ◽  
Erkki Elonen ◽  
Arne Kolstad ◽  
Anna Laurell ◽  
Lone B. Pedersen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
High Dose ◽  
Clinical Relapse ◽  
Relapse Free Survival ◽  
Molecular Remission ◽  
Free Survival ◽  
Mantle Cell ◽  
Disease Free

Abstract The 2nd. Nordic Lymphoma Group mantle cell lymphoma (MCL2) protocol has demonstrated the importance of Ara-C and Rituximab in the induction chemotherapy and stem-cell mobilisation before high-dose therapy and autologous stem-cell transplant (1). By July 2005, 128 patients (83% stage IV) had completed protocol treatment consisting of 3 series of R-CHOP and 3 series of R-Ara-C, stem-cell harvest and high-dose therapy with BEAM/BEAC with ASCT. The 5-year failure-free and overall survival is 50% and 83% respectively, significantly higher than the historic control group of the Nordic MCL1 protocol with the same treatment without HD-Ara-C and Rituximab (P&lt;0.0001). Patients with a molecular marker (t(11;14) or clonal IgH rearrangement) identified at the time of diagnosis in bone marrow and blood, undergo regular molecular follow-up posttransplant,. Patients who turn PCR-positive or increase their qPCR signal, without clinical disease, are offered preemptive treatment with Rituximab 375 mg/m2 Wx4. Of 75 patients with molecular markers who had completed treatment, 55 remain PCR-negative and 20 have become/remained PCR-pos. posttransplant. Clinical relapse ocurred significantly more often in the latter group (11 of 20) than in the PCR-neg. patients (4 of 55) (P&lt;0.0001) (Fig.1). Ten of the 20 PCR-positive patient did not receive preemptive rituximab: five due to immediate clinical relapse, 2 due to stable qPCR signals, one due to protocol error and two await treatment. Of 10 patients who did receive preemptive rituximab 8 again became PCR-negative and 2 remain PCR-positive. Six of the 10 Rituximab treated patients remain in clinical and molecular remission 200–600 days after the Rituximab treatment (Fig. 2). Conclusions: In MCL, molecular relapse is a harbinger of imminent clinical relapse, whereas continuous molecular remission is associated with prolonged disease-free survival (89% at 4 years) Rituximab preemptive treatment can reinduce molecular remission and may delay clinical relapse. Following molecular relapse, only Rituximab treated patients (6 of 8 evaluable) remain disease-free. FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 1. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL ACC. TO MOLECULAR STATUS POSTTRANSPALNT FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE. FIG. 2. NORDIC NCL-2 PROTOCOL: RELAPSE-FREE SURVIVAL FROM TIME OF MOLECULAR RELAPSE.

Moderately hypofractionated radiotherapy for localized prostate cancer: Long-term outcomes for 854 consecutive patients treated over 10 years (70 Gy in 2.5 Gy/fraction).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 78-78
Author(s):  
Omar Y. Mian ◽  
Ibrahim Abu-Gheida ◽  
Rupesh Kotecha ◽  
Michael A. Weller ◽  
Chandana A. Reddy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Localized Prostate Cancer ◽  
Oncologic Outcomes ◽  
Hypofractionated Radiotherapy ◽  
Clinical Relapse ◽  
Intermediate Risk ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Number Of Patients ◽  
Grade 3

78 Background: Moderately hypofractionated radiotherapy has been increasingly adopted in the management of localized prostate cancer (PCa). We report 10-year outcomes for patients treated with intensity modulation radiation therapy (IMRT) for localized PCa with 70 Gy in 28 fractions at 2.5 Gy/fraction. Methods: This retrospective study included 854 consecutive patients with localized PCa treated with image-guided moderately hypofractionated IMRT at a single institution between 1998 and 2012. Patients with a single intermediate-risk factor were considered to have favorable intermediate-risk (FIR) disease; multiple intermediate-risk factors were considered unfavorable (UIR). Biochemical relapse free survival (bRFS), clinical relapse free survival (cRFS), overall survival (OS) and PCa specific mortality (PCSM) were analyzed used Kaplan-Meier analysis. Grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded (CTCAE v4.03). Results: The median follow-up was 11.3 years (Max. 19 years). For patients with low-risk (LR, 31%), FIR (28%), UIR (12.5%), and high-risk (HR, 28.5%) disease the 10 year bRFS rates were 88%, 78%, 71% and 42%, respectively (p < 0.0001). The number of patients receiving no ADT, 1-6 months, or > 6 months of ADT were 39%, 50%, and 11%, respectively, reflecting practice patterns during this treatment period. The 10-year cRFS were 95%, 91%, 85% and 72% for patients with LR, FIR, UIR, and HR, respectively (p < 0.0001). The 10-year actuarial OS rate was 69% (95% CI 66-73%) and the 10-year PCSM was 6.8% (95% CI 5.1-8.6%) overall. For patients with LR, FIR, UIR and HR disease, the 10 year PCSM rates were 2%, 5%, 5% and 15%. 10-year cumulative incidence of grade ≥3 GU and GI toxicity was 2% and 1%, respectively. Multivariate analysis identified associations between clinical variables (ADT use, PSA nadir < 0.5ng/ml, and ISUP Grade Group) and bRFS, cRFS, and PCSM. Conclusions: Moderately hypofractionated IMRT with daily image guidance for localized PCa demonstrates favorable 10-year oncologic outcomes with a low incidence of toxicity for patients across all risk groups.

scholarly journals Intravenous tacrolimus is a superior induction therapy for acute severe ulcerative colitis compared to oral tacrolimus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hiromichi Shimizu ◽  
Toshimitsu Fujii ◽  
Kenji Kinoshita ◽  
Ami Kawamoto ◽  
Shuji Hibiya ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Cohort Study ◽  
Primary Outcome ◽  
Remission Rate ◽  
Survival Rates ◽  
Efficacy And Safety ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
Intravenous Corticosteroid

Abstract Background Intravenous corticosteroid is the mainstay for managing acute severe ulcerative colitis, but one-third of patients do not respond to intravenous corticosteroid. Tacrolimus, a salvage therapy before colectomy, is usually orally administered, though its bioavailability is low compared intravenous administration. The efficacy of intravenous tacrolimus has not been widely studied. Aim To determine the efficacy and safety of intravenous tacrolimus for the treatment of acute severe ulcerative colitis. Methods Eighty-seven hospitalized acute severe ulcerative colitis patients were enrolled for a prospective cohort study between 2009 and 2017. Sixty-five patients received intravenous tacrolimus and 22 received oral tacrolimus. The primary outcome was the achievement of clinical remission within 2 weeks. Relapse and colectomy incidence and adverse events were assessed at 24 weeks. Results Response rates of both treatments exceeded 50% but were not significantly different. The remission rate was higher in intravenous tacrolimus compared with oral tacrolimus. At 24 weeks, oral and intravenous tacrolimus showed similar relapse-free survival rates; however, colectomy-free survival rates were higher in intravenous tacrolimus compared with oral tacrolimus. Conclusions Patients receiving intravenous tacrolimus achieved superior remission and colectomy-free survival rates compared with patients receiving oral tacrolimus. Safety was similar between the two treatments.

scholarly journals Effectiveness and Nephrotoxicity of Long-Term Tacrolimus Administration in Patients with Ulcerative Colitis

2020 ◽  
Vol 9 (6) ◽  
pp. 1771
Author(s):  
Keiichi Haga ◽  
Tomoyoshi Shibuya ◽  
Kei Nomura ◽  
Koki Okahara ◽  
Osamu Nomura ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Renal Function ◽  
Medical Records ◽  
Careful Monitoring ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Effective Option ◽  
Term Administration ◽  
Potential Use

Background: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. Methods: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. Results: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. Conclusion: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration.

Gene Expression Profiling Predicts Clinical Outcomes in Newly Diagnosed Multiple Myeloma Patients in a Standard of Care Setting

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5628-5628 ◽  
Author(s):  
Catherine M Claussen ◽  
Hans Lee ◽  
Jatin J. Shah ◽  
Tiffany Richards ◽  
Nina Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Outcomes ◽  
Expression Profiling ◽  
Care Setting ◽  
Standard Of Care ◽  
Gene Gain ◽  
Time To Event ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Patient Groups

Abstract Introduction: Multiple Myeloma is a heterogeneous cancer that affects the bone marrow. Given this heterogeneity, we aimed to elucidate the role of gene expression profiling (GEP) in identifying different MM subtypes and explore their relationship to clinical outcomes in a standard of care setting. Methods: We retrospectively analyzed all NDMM patients with baseline GEP analysis. 55 patients from April 2014 until March 2016 were identified and included in our analysis. GEP was performed using CD138+ cells from bone marrow samples through MyPRS® (Signal Genetics, Little Rock, AR). Fisher's exact test was used to evaluate the associations between two categorical variables. The Wilcoxon rank sum test was used to evaluate the difference in continuous variables between patient groups. Kaplan-Meier method was used to estimate the time to event endpoints including relapse free survival (RFS) and overall survival. The log-rank test was used to evaluate the differences in the time to event endpoints between/among patient groups. Univariate Cox proportional hazards model was used to evaluate the association between a continuous variable and relapse free survival. Results: Median age was 61 (38-76). Patients presented with lytic lesions (80%), anemia (78%), kidney dysfunction (24%) and hypercalcemia (31%). One patient did not meet CRAB criteria, but had 60% plasma cells in the bone marrow and an involved/uninvolved sFLC ratio of 199. All patients were treated with bortezomib (88%) or carfilzomib (12%) initial therapy in combination with lenalidomide (83%) or cyclophosphamide (17%). All patients received triple therapy as initial treatment, with 60% of patients receiving an upfront autologous transplant. With median follow-up of 12 months (1.64-24.54 months) 75% of patients had not relapsed and median overall survival had not been reached. 13 (24%) patients were characterized as high risk (HR) by GEP. GEP risk category predicted RFS (p=0.0014) in this series of patients (Fig. 1). Table 1 shows GEP risk subtypes with clinical outcomes and association to FISH abnormalities. We previously reported that HR FISH abnormalities are present in GEP low risk (LR) patients. LR GEP patients with CKS1B gene gain by FISH (n=9, 23%) had 100% RFS at 21 months, while 60% of HR GEP patients with CKS1B gene gain had relapsed by 24 months (p=0.0297, Fig. 2). All patients with HR GEP and 17p deletion relapsed by 14 months whereas only one patient with LR GEP and 17p deletion died 1 year from diagnosis, with an unknown cause of death (p=0.18, Fig. 3). Conclusion: Cytogenetics and FISH are still the current standard of care to predict prognosis in NDMM, direct care and inclusion in clinical trials. This study in a standard of care setting shows that GEP further refines prognosis in patients with HR FISH abnormalities. Future studies in larger cohorts of patients are warranted to confirm our findings. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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