Prognostic Factors For Progression Research Articles

Prognostic factors for progression of simple steatosis to steatohepatitis in patients with persistent normal and elevated liver enzymes

IntroductionNonalcoholic fatty liver disease (NAFLD) is characterized by a wide spectrum of liver damage, ranging from simple macrovesicular steatosis to steatohepatitis [nonalcoholic steatohepatitis (NASH)], cirrhosis, and liver carcinoma.AimThis study assessed reliable markers of NASH such as clin

Relapse of autoimmune pancreatitis following surgery: A case report

s / Pancreatology 12 (2012) 502–597 532 Results: 135 consecutive patients were included: 8.9% were classified in group 1, 84.4% n group 2 and 6.7% in group 3. Median Ki67was 7% (range 1%-95%). Median PFS was 13 months. Different PFS was observed for: G grading (P<0.001; 5-yr PFS G1/G2/G3: 18.9%/18.3%/not reached) and metastatic pattern (P1⁄4 0.05; 5-yr survival group 1/2/3: 25.4%/18.4%/11.1%). Significant risk factors were: Ki67 (for each increasing unit: HR 1.03; P<0.001), metastatic pattern (HR 1.80; P1⁄4 0.02), G Grading (HR: 2.22; P<0.001). At multivariate analysis, prognostic factors for progression were both Ki67 (HR 1.03, P<0.001) and metastatic pattern (HR 1.79; P1⁄4 0.02). Conclusion: In patients affected by metastatic PNETs, Ki67 and metastatic pattern are two independent risk factors for disease progression.

Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma

Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.

Subtypes of Amnestic Mild Cognitive Impairment Based on Memory Impairment Pattern and Its Potential Clinical Significance

|| Background: Episodic memory impairment can be subdivided into two subtypes, encoding failure vs. re- trieval deficit. We defined two subtypes of amnestic mild cognitive impairment (aMCI) according to rec - ognition performance on the memory test: aMCI with encoding failure or aMCI-E and aMCI with retrieval deficit or aMCI-R. We hypothesized that compared to aMCI-R, subjects with aMCI-E are more likely to convert to Alzheimer's disease, as encoding failure suggests that medial temporal lobes are affected ear- ly in the disease process. We also investigated whether aMCI-E can be a predictor for progression to AD. Methods: Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, a total of 397 aMCI subjects were included. APOE genotype, cerebrospinal fluid (CSF) fluid biomarkers, and a set of neuropsychological measures were also collected. Unadjusted and adjusted odds ratios were calculated to predict the conversion to AD dementia. The Spearman's rs test was used to measure the degree of correlation between aMCI subtypes and the prognostic factors for progression to AD. Results: Among the 397 subjects, 209 (52.6%) subjects were classified into aMCI-E and 188 (47.4%) into aMCI-R. One hun - dred two (48.8%) subjects with aMCI-E and 57 (30.3%) of those with aMCI-R progressed to AD (unad- justed odds ratio = 2.19 with 95% confidence interval (CI) 1.45-3.31) over 3 years. However, when adjust - ed odds ratio by a logistic regression was calculated, probability value of aMCI-E disappeared with the odds of conversion by of 1.47 (95% CI 0.89-2.43). There were statistically significant correlations be - tween aMCI-E subtype and MMSE, CDR Memory, RAVLT delayed recall, CSF biomarkers, and geno- types. Conclusions: This analysis did not show that aMCI-E is an independent prognostic factor to predict the progression to AD. However, this subtype significantly correlates with other prognostic factors for pro - gression. This may suggest that aMCI-E might be a later stage of aMCI and aMCI-R an earlier stage which might be a better target than aMCI-E for therapeutic intervention. Further studies are needed to validate this conjecture.

Thymidine kinase and cancer monitoring

Thymidine kinases (TK) have a key function in the synthesis of DNA. Two isoenzymes have been characterized: TK1 is cell cycle-dependent and present in the cytoplasm whereas TK2 – located in mitochondria – is cell cycle-independent. The diagnostic and prognostic role of TK1 has recently been investigated. TK1 might be helpful for screening and monitoring of human malignancies. TK1 may also serve as a prognostic factor for progression. Herein, we summarize the status of TK1 for cancer monitoring and point out its use as a proliferation marker. A comprehensive overview about the association of TK-1 with various entities is given.

Progression From Acute to Chronic Pancreatitis

Knowledge of the natural course of acute pancreatitis (AP) and risk of progression to chronic pancreatitis (CP) is limited. The aims were to describe: (1) the incidence of progression from AP to CP, (2) prognostic factors for progression, and (3) the natural course and mortality of progressive AP. During 1977 to 1982, patients admitted to hospitals in Copenhagen with a diagnosis of AP or CP were included in a prospective cohort and followed up by the Danish registries in 2008. The subcohort analyses comprised 352 AP patients. Progressive AP was found in 85 patients (24.1%) during follow-up; 48.2% developed from alcoholic AP, 47.0% from idiopathic AP, and 4.8% from other causes. The mortality rate for patients with progressive AP was 2.7 times higher than in patients with nonprogressive acute pancreatitis, and 5.3 to 6.5 times higher than in the background population. In Cox regression analyses corrected for age, only smoking was of significance for the progression from AP to CP. Acute pancreatitis can progress to CP, not only from alcoholic but also from nonalcoholic AP. Smoking was the strongest risk factor associated with progression. The mortality rate for these patients was 5 to 6 times the mortality rate in the population.

PND61 EVALUATION OF CONSISTENCY BETWEEN MULTIPLE SCLEROSIS REGISTRY PUBLICATIONS

Multiple Sclerosis (MS) registries collect patient-level longitudinal data with the aim of improving our understanding of MS. These databases have provided extensive studies on the natural progression of MS. The purpose of this study is to assess how disease progression has been estimated and assess the consistency in methodology and results. The publications of 10 major MS Registry websites were searched, followed up with keyword searches in Embase and Pubmed. Population-based natural history studies on disease progression were included. Primary and non-primary endpoints, such as Expanded Disability Status Scale (EDSS) outcomes as a measure of progression, were extracted in addition to statistical methodologies. We evaluated the consistency between studies in terms of endpoints and statistical methodology. Our search identified 23 studies, of which nine met the inclusion criteria. The majority of papers utilized the Kaplan-Meier Survival technique to estimate time until disease endpoints and Cox proportional hazard models to determine prognostic factors. Lack of standards in reporting results prevented a global comparison. The most commonly reported endpoint was median time to EDSS six for MS or relapsing-remitting MS patients, enabling comparison between six studies. Values were reported between 11.9 to 27.9 years. Excluding studies prior to 1999, the median time to EDSS six was between 20-27.9 years. Results reported from the European based Lyon and LORSEP registries were consistent (20-24 years), while studies in Canada and Germany showed greater disparity. Common prognostic factors included age and type of MS at onset. Lack of international standards for reporting outcomes in natural history progression hinders comparisons between studies, especially between the United States and Europe. While there is some consensus between registries regarding prognostic factors for progression, not all agree. Heterogeneity in underlying characteristics of the populations, evolution in best supportive care and access to treatments could all contribute.

Association of PTEN loss with outcome of patients (pts) with early high-risk prostate cancer (CaP) treated with adjuvant docetaxel following radical prostatectomy (RP).

43 Background: Loss of the PTEN tumor suppressor and subsequent activation of the PI3K pathway is common and has potential clinical and therapeutic value in CaP. We examined the PTEN status of primary tumors in pts who underwent adjuvant docetaxel tx in a prospective clinical trial. Methods: Of the 77 pts enrolled in a prospective multi-institutional adjuvant docetaxel trial (TAX 2501, J Urol 2007), we prospectively collected 56 primary tumor pathology specimens suitable for analysis of PTEN status by immunoreactivity (IHC) and/or fluorescence in situ hybridisation (FISH) assay. Protocol defined progression included a PSA of ≥ 0.4 ng/mL, radiological/pathological evidence of recurrent disease or death from any cause. Univariate and multivariable analyses based on the Cox proportional hazards regression model were used to analyze the independent association of PTEN and other known prognostic factors with progression free survival (PFS). Results: PTEN loss was observed in 37/56 pts (66%). Pts with PTEN loss vs detectable PTEN were balanced regarding clinical stage, combined Gleason score, seminal vesicles and surgical margins involvement, and lymph nodes status. Pts with a detectable PTEN had a significantly higher pre-RP PSA (median 14 vs 8.6 ng/mL, p=0.015). 41/56 (73.2%, median followup of 37.5 months, range 10.4 to 44.5) progressed with an overall median PFS of 13 months (mos) (95% CI 9.8–15.8). Independent prognostic factors of progression by multivariate analysis were: seminal vesicles involvement (HR 2.19, p=0.024), combined Gleason score 9–10 (HR 2.46, p=0.027) and PTEN loss (HR 2.36, p=0.037). PFS on pts without PTEN loss (median not reached at a followup time of 37.5 mos, range 10.4–44.5 mos) was significantly longer (log rank test, p = 0.026) compared to those with undetectable PTEN (median PFS 12.9 mos, 95% CI 9.7–15.3). Conclusions: PTEN loss may be an independent prognostic factor associated with poorer outcome of pts with early high-risk CaP treated with adjuvant docetaxel following RP. These findings may have important prognostic and therapeutic implications in CaP. No significant financial relationships to disclose.

Clinical course, diagnosis and treatment of gastrointestinal stromal tumors

The article summarizes up-to-date data of the pathogenesis, diagnosis, and treatment conceptions of the stromal tumors of gastrointestinal tract (GIST). Prognostic factors for progression (recurrence or metastasis) for GIST are reported. Special attention is given to immuno-histochemical method of diagnostics and target therapy for these kinds of tumors. We present the case history of successful operation in a patient with giant intestinal stromal tumor of the stomach, sprouting into neighbouring organs and tissues.

The Relationship Between Human Papillomavirus Status and Other Molecular Prognostic Markers in Head and Neck Squamous Cell Carcinomas

To evaluate the relationship between human papillomavirus (HPV) status and known prognostic makers for head and neck cancers including tumor hypoxia, epidermal growth factor receptor (EGFR) expression and intratumoral T-cell levels and to determine the prognostic impact of these markers by HPV status. HPV status in 82 evaluable head and neck squamous cell carcinomas patients was determined by pyrosequencing and related to p16(INK4a) staining and treatment outcomes. It was correlated with tumor hypoxia (tumor pO(2) and carbonic anhydrase [CAIX] staining), EGFR status, and intratumoral lymphocyte expression (CD3 staining). Forty-four percent of evaluable tumors had strong HPV signal by pyrosequencing. There was a significant relationship between strong HPV signal and p16(INK4a) staining as well as oropharynx location. The strong HPV signal group fared significantly better than others, both in time to progression (TTP, p = 0.008) and overall survival (OS, p = 0.004) for all patients and for the oropharyngeal subset. Positive p16(INK4a) staining was associated with better TTP (p = 0.014) and OS (p = 0.00002). There was no relationship between HPV status and tumor pO(2) or CAIX staining. However, HPV status correlated inversely with EGFR reactivity (p = 0.0006) and directly with CD3(+) T-lymphocyte level (p = 0.03). Whereas CAIX and EGFR overexpression were negative prognostic factors regardless of HPV status, CD3(+) T-cell levels was prognostic only in HPV(-) tumors. HPV status was a prognostic factor for progression and survival. It correlated inversely with EGFR expression and directly with T-cell infiltration. The prognostic effect of CAIX and EGFR expression was not influenced by HPV status, whereas intratumoral T-cell levels was significant only for HPV(-) tumors.

Recurrence at Three Months and High-grade Recurrence as Prognostic Factor of Progression in Multivariate Analysis of T1G2 Bladder Tumors

To evaluate the risk factors for disease progression in the frequent subgroup of Stage T1G2 (World Health Organization 1973) bladder tumors using an analysis of a large cohort of patients with Stage T1G2 disease. A cohort of 616 patients with Stage T1G2 were treated with transurethral resection and random bladder biopsies. The mean follow-up was 4.2 years. Univariate and multivariate analyses were done using Cox regression analysis. The independent variables were multiplicity, association with carcinoma in situ (CIS), tumor size, tumor recurrence at 3 or 6 months, tumor grade, and association with CIS at first recurrence. The dependent variable was progression to muscle-invasive disease. Progression to muscle-invasive disease was identified in 28 of the 616 patients (4.5%). On multivariate analysis, when considering recurrence at 3 months, this factor was the principal prognostic factor, with a relative risk of 4.0 (95% confidence interval 1.2-13.3), followed by the presence of high-grade disease or CIS at first recurrence (relative risk 2.8, 95% confidence interval 1.3-5.8) and CIS associated with the primary tumor (relative risk 1.8, 95% confidence interval 1.1-2.9). When considering recurrence at 6 months, more prognostic factors were involved for progression, including as multiple tumors, CIS associated with the primary tumor, recurrence at 6 months, and the presence of high-grade disease or CIS at the first recurrence. In primary urothelial T1G2 bladder cancer, recurrence at 3 months was the main prognostic factor related to progression. Additional factors were the association of CIS with the primary tumor and the presence of high-grade disease and/or CIS at first recurrence.

P53 mutations in urinary bladder cancer patients from Central Poland

The present study aimed at detection of P53 gene mutations in cells of urinary bladder neoplasms, as the mutations may be regarded as an independent prognostic factor for progression and recurrence of tumours. In the study, 82 patients with clinically diagnosed urinary bladder tumour were included. The control was composed of DNA samples from urine and blood of 202 healthy patients. Exons 5-8 of the P53 gene were screened for mutations by using multitemperature single-strand conformational polymorphism (MSSCP) analysis. Samples with abnormal MSSCP patterns were subjected to direct sequencing. The frequency of mutations in exons 5-8 of the P53 gene in patients with bladder cancer was lower (3.3% in grade G1, 24% in G2, and 39% in G3) than the data reported in the literature. We found a higher percentage of polymorphism at codon 213 of the P53 gene in bladder cancer patients (6%), compared with the values in the reference group (2.5%). These results were matched with those of the loss of heterozygosity (LOH) analysis. In conclusion, mutations were found mainly in more advanced histopathological and clinical stages of the disease and at the CIS stage (carcinoma in situ). It cannot be excluded that the observed polymorphism at codon 213 may be a predisposing factor for urinary bladder carcinoma development.

Predicting factors for severity of rheumatoid arthritis: a prospective multicenter cohort study of 172 patients over 3 years

Rheumatoid arthritis may take an unfavourable course leading to rapid functional decline in a certain percentage of patients. Early identification of these patients is desirable. The aim of this study was to evaluate clinical and laboratory parameters for their value in the prediction of bad outcome. A total of 172 patients with early arthritis were followed for 3 years. Higher initial values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum concentration of cartilage oligomeric matrix protein, Health Assessment Questionnaire score, Larsen score of feet, disease activity score, and swollen and tender joint count predicted worse outcome. An association with the presence of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be established. We conclude that prognosis in an individual with rheumatoid arthritis depends on many factors. The determination of independent prognostic factors for progression of rheumatoid arthritis is a valuable tool in early arthritis to select patients for more aggressive therapy.

Prognostic Factors for Progression of Visual Field Damage in Patients with Normal-Tension Glaucoma

Prognostic Factors for Progression of Visual Field Damage in Patients with Normal-Tension Glaucoma

Prognostic Factors for Progression of Visual Field Damage in Patients with Normal-Tension Glaucoma

Prognostic Factors for Progression of Visual Field Damage in Patients with Normal-Tension Glaucoma

Serum levels of sCD137 (4‐1BB) ligand are prognostic factors for progression in acute myeloid leukemia but not in non‐Hodgkin's lymphoma

CD178 (Fas/APO-1 ligand) and CD137 ligand (CD137L) have previously been described in sera of patients with various malignancies and play an important role in the pathogenesis of various diseases. Recently, we demonstrated that low levels of soluble (s) CD137L and high levels of sCD178 correlate significantly with a long progression free survival in patients with myelodysplastic syndrome (MDS). In this study, we correlated sCD137L and sCD178 levels in sera of 42 samples of patients with acute myeloid leukemia (AML) and 46 samples of patients with non-Hodgkin's lymphoma (NHL) with stages, subtypes, and the clinical course of the diseases and determined cut-off values with maximum probability for significant differentiation between cases with higher/lower probability for progress free survival. In contrast to patients with MDS, surprisingly no correlation between sCD178 levels and different subtypes and stages or with prognosis in AML or NHL were observed. Regarding sCD137L, NHL-patients displayed lower levels compared with AML. Statistically significant higher median levels of sCD137L are present in patients with undifferentiated AML (M1/M2, 1,470 pg/mL), poor cytogenetic risk (288 pg/mL) and higher levels of BM-blasts (186 pg/mL) compared with patients with monocytoid AML (M4/M5, 89 pg/mL), intermediate cytogenetic risk (59 pg/mL) and lower levels of BM-blasts (14 pg/mL) respectively. Furthermore, in AML patients sCD137L levels correlate significantly with the probabilities to achieve complete remission (CR), stay in CR or with progress of the disease. Taken together, our data demonstrate that sCD137L can be used as a prognostic factor not only in MDS but also in AML.

Metallothionein – overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients

Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. In the last decades, it was shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and is combined with a poor prognosis. In this prospective study, we examined the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. Between 1993 and 2004, 3386 patients with primary cutaneous melanoma were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. In all, 1270 patients could be followed up for further statistical analysis (Fisher's exact test, Mantel–Haenszel χ2 test, Kaplan–Meier curves). The MT data of disease-free interval and overall survival were compared univariately and multivariately in Cox regression analysis. Immunohistochemical overexpression of MT in tumour cells of patients with primary melanoma (310 of 1270; 24.4%) was associated with a higher risk for progression (117 of 167; 70.1%) and reduced survival (80 of 110; 72.7%) of the disease (P<0.0001). Similarly, Kaplan–Meier curves gave highly significant disadvantages for the MT-positive group. Univariate analysis (relative risk 7.4; 95% confidence interval (CI) 5.2–10.2; P<0.0001 for progression; relative risk 7.1; 95% CI 4.7–10.9; P<0.0001 for survival), as well as multivariate analysis with other prognostic markers resulted in MT overexpression as a highly significant and independent factor for prognosis in primary melanoma.

Abnormal Cytogenetics and Significant Bone Marrow Plasmacytosis are Predictive of Early Progression and Short Survival in Patients with Low Tumor Mass Asymptomatic Multiple Myeloma

In order to evaluate the prognostic factors for progression and survival in patients with a low tumor mass asymptomatic multiple myeloma (MM), we studied 59 patients who had a long term follow-up. Cytogenetic abnormalities (using conventional cytogenetics) were observed in 14 out of 45 analyzable patients (31%). An abnormal karyotype and a bone marrow (BM) plasmacytosis > 15% were found to be adverse prognostic factors for progression in univariate and multivariate analysis.

Serum Levels of CD137 Ligand and CD178 are Prognostic Factors for Progression of Myelodysplastic Syndrome

Excess apoptosis leading to ineffective hematopoiesis is a common feature of myelodysplastic syndrome (MDS). CD178 (Fas ligand/APO-1 ligand) and CD137 ligand (CD137L), 2 molecules involved in the regulation of apoptosis, have previously been found in sera of patients with malignancies and have been hypothesized to participate in the pathogenesis of various diseases. We analyzed sera of patients with MDS and found that while time to progression of MDS correlated with the IPSS score there was no correlation of CD137L or CD178 serum levels with this score or with karyotype, bone marrow blast count or cytopenia. However, when cut-off-values for significant differentiation between cases with higher/lower levels of these molecules were determined we found that high levels of soluble CD137L (sCD137L) and low serum levels of soluble CD178 (sCD178) correlate with statistical significance to rapid progression of disease as estimated by log-rank-test. Conversely, low levels of sCD137L and high levels of sCD178 correlate significantly with prolongation of time to progression of disease. Our results indicate that serum levels of sCD137L and sCD178 represent valuable novel indicators for prognosis and disease progression and may be a useful parameter for treatment decisions in patients with MDS.

Metallothionein-overexpression as a prognostic factor for progression and survival in melanoma. A prospective study on 520 patients.

Metallothioneins (MTs) are ubiquitous proteins with high affinity for heavy metal ions, e.g. zinc, copper and cadmium. In the last decade it has been shown that MT overexpression in a variety of cancers is associated with resistance to anticancer drugs and radiotherapy, and with a poor prognosis. To examine the role of MT overexpression in melanoma patients as a prognostic factor for progression and survival. In a prospective cohort study 760 patients with primary cutaneous melanoma were investigated over 5 years (1993-98) by using a monoclonal antibody (E9) against MT on routinely fixed and paraffin-embedded tissues. In total, 520 patients were able to be followed up for progression of their disease or death due to melanoma and were included for statistical analysis (Fisher's exact test, Mantel-Haenszel chi2 test, Kaplan-Meier curves). MT data, progress-free interval and overall survival were compared univariately and multivariately with other prognostic factors, e.g. Breslow thickness, Clark level, ulceration, localization, age and gender (Cox regression analysis). The immunohistochemical overexpression of MT in tumour cells (cut-off level > 10% of all tumour cells) in patients with primary melanoma (156 of 520; 30%) was associated with a higher risk for progression of the disease (33 of 45; 73%) and reduced survival (24 of 30; 80%) than MT-negative lesions [364 of 520 (70%), 12 of 45 (27%) and six of 30 (20%), respectively (P < 0.0001)]. Similarly, Kaplan-Meier tumour-free survival and overall survival curves for the comparison of MT-positive and MT-negative tumours gave highly significant advantages for the MT-negative group. In a univariate analysis (comparison with Breslow thickness: relative risk 2.9, 95% confidence interval, CI 1.46-5.76, P = 0.0023 for progression; relative risk 4.19, 95% CI 1.73-10.19, P = 0.0015 for survival), as well as in a multivariate analysis with other prognostic markers, MT overexpression turned out to be a highly significant and independent factor for prognosis in primary melanoma. MT overexpression in primary melanoma is associated with an increased risk for disease progression. This marker is independent from Breslow thickness and helps to identify those thin melanomas (< 1.5 mm) that are at increased risk of progression. Moreover, the immunohistochemical staining of paraffin material is a cheap, easy and widely available technique to gain these results.