Risk Factors For Advanced Disease Research Articles

282 Lifestyle and demographic risk factors in mycosis fungoides and Sezary syndrome: A single institution cohort study

Background: Mycosis fungoides (MF) and Sezary syndrome (SS) are common subtypes of cutaneous T-cell lymphoma (CTCL). Risk factors and impact on quality of life (QoL) are poorly understood. Previous studies of CTCL risk factors have not analyzed disease stage, severity, and QoL together. We explored associations between demographic and lifestyle factors and these parameters. Methods: A cohort study was conducted at a large CTCL multidisciplinary clinic from April 2019 to December 2020. REDCap surveys were administered to 115 MF/SS patients, investigating 11 demographic and lifestyle factors. QoL was evaluated using Skindex-29; pain and itch with Likert scales. Disease severity was assessed using the modified Severity Weighted Assessment Tool (mSWAT). Factors were compared using t-test, chi-squared, and linear or logistic regression models. Results: History of chemical exposures was associated with greater disease severity (p=0.034) and worse QoL (p=0.005), but not with pain/itch severity (p=0.118). Disease severity and stage were associated with worse QoL (both p<0.001). There were significant racial differences in early (IA-IIB) versus late (IIIA-IV) stage disease (p=0.034) and QoL (p=0.039). There was a significant relationship between smoking and disease stage (p=0.028) but not severity (p=0.360). Obesity was correlated with disease severity (p=0.021), but not with stage or QoL (p=0.582; 0.232). Conclusion: We provide an analysis of patient lifestyle and demographic factors in the context of MF/SS severity, stage, and QoL. We identified race and smoking as potential risk factors for advanced disease, and chemical exposures and obesity for increased disease severity. Worse QoL was significantly associated with a history of chemical exposure, severe pain/itch, race, and stage. Identification of demographic and lifestyle associations in MF/SS will enable physicians to provide more individualized patient care and education.

Interplay of PNPLA3 and HSD17B13 Variants in Modulating the Risk of Hepatocellular Carcinoma among Hepatitis C Patients

A single-nucleotide polymorphism causing a C to G change in the PNPLA3 gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17β-hydroxysteroid dehydrogenase type 13 (HSD17B13) mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for PNPLA3 and HSD17B13 gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of PNPLA3 G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC (p = 0.007). When the HSD17B13:TA status of these patients was taken into account, the abovementioned trend was strengthened among HSD17B13 major allele homozygotes and completely blunted among carriers of the minor allele (p = 0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the PNPLA3 minor allele and HSD17B13 major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR = 2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination PNPLA3 minor allele and HSD17B13 major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.

Global Retinoblastoma Presentation and Analysis by National Income Level

Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

MP11-09 METABOLIC SYNDROME INCREASES THE RISK OF UPGRADING EPSTEIN 2015 GLEASON SCORE IN PATIENTS WITH PROSTATE CANCER ON BIOPSY: A RADICAL PROSTATECTOMY MULTICENTER COHORT STUDY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II1 Apr 2018MP11-09 METABOLIC SYNDROME INCREASES THE RISK OF UPGRADING EPSTEIN 2015 GLEASON SCORE IN PATIENTS WITH PROSTATE CANCER ON BIOPSY: A RADICAL PROSTATECTOMY MULTICENTER COHORT STUDY Cosimo De Nunzio, Giuseppe Simone, Costantino Leonardo, Riccardo Mastroianni, Collura Devis, Giovanni Muto, Michele Gallucci, Riccardo Lombardo, Carlo De Dominicis, and Andrea Tubaro Cosimo De NunzioCosimo De Nunzio More articles by this author , Giuseppe SimoneGiuseppe Simone More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Collura DevisCollura Devis More articles by this author , Giovanni MutoGiovanni Muto More articles by this author , Michele GallucciMichele Gallucci More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Carlo De DominicisCarlo De Dominicis More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.375AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aim of our study was to investigate the association of metabolic syndrome (Mets) with the risk of upgrading and down grading in patients with PCA on biopsy using the new Epstein Gleason score classification in a series of men undergoing radical prostatectomy(RP). METHODS Between 2012 and 2016, 400 patients with clinically localized PCa were treated with retropubic radical prostatectomy (RRP) at three tertiary referral centres. Body mass index (BMI) and waist circumference were measured before RRP. Blood samples were collected for PSA, fasting glucose, triglycerides and HDLs. Blood pressure was recorded. All the patients underwent a 12 core trans-rectal ultrasound-guided prostate needle biopsy in the same referral center where the radical prostatectomy was performed. Biopsy specimens as well as radical prostatectomy specimens were graded according to 2015 Epstein Gleason grading system and then compared. Clinically significant upgrading was defined as: Epstein score raising from = 2 to =3 or from 3 to 5. As well clinically significant downgrading was defined as: Epstein score decreasing from =3 to = 2 or from 5 to = 3. The accuracy of the biopsy for patients with and without MetS was determined using the kappa coefficient of agreement: <0.4 poor agreement, 0.4-0.75 good agreement and > 0.75 excellent agreement. MetS was defined according to Adult Treatment Panel III (ATPIII). RESULTS Median age and preoperative PSA levels were 65 years (IQR: 60-70) and 7.4 ng/ml (IQR: 5.5-10.9), respectively. Median BMI was 26.0 kg/m2 (IQR: 24.3-28.0). On pathological evaluation 163/400 (40,8%) had locally advanced disease (=pT3a), 115/400 (28,7%) had high grade disease and 15/400 (3,8%) had nodal involvement. Overall 148/400 (37%) patients presented the MetS. Patients with MetS presented higher upgrading rates (33/148:22.3% vs 25/252:9.9%; p = 0.001) on RRP specimens when compared to patients without MetS while downgrading rates were similar (13/148 : 8.7% vs 18/252: 7.1 %; p=0.566). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens was worst for patients with MetS when compared to patients without MetS (k= 0.439±0.071 vs k= 0.553±0.071). Patients with MetS also presented a significantly higher rates of pT3 disease (84/148:56.8% vs 79/252:31,3%, p=0.001) and Epstain Gleason score > 2 (61/148:41% vs 54/252, p=0.001), data confirmed on multivariate analysis (OR: 2.818; CI: 1.774-4.476, p=0.001 and OR: 3.577; CI: 2.230-5.737, p=0.001respectively) CONCLUSIONS In this multicenter radical prostatectomy cohort, MetS represents a significant risk factor for advanced disease and high grade disease. Nonetheless patients with MetS carry a higher risk of upgrading on RRP specimens. Further studies with a pathological review and reclassification of the specimens are needed to confirm our data. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e130-e131 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Cosimo De Nunzio More articles by this author Giuseppe Simone More articles by this author Costantino Leonardo More articles by this author Riccardo Mastroianni More articles by this author Collura Devis More articles by this author Giovanni Muto More articles by this author Michele Gallucci More articles by this author Riccardo Lombardo More articles by this author Carlo De Dominicis More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Utility of Noninvasive Scores in Assessing the Prevalence of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Type 2 Diabetic Patients.

The aim of our study is to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and advanced hepatic fibrosis in patients with type 2 diabetes mellitus (T2DM) using simple noninvasive scores. In individuals with T2DM, there is a very high prevalence of NAFLD. Moreover, T2DM is a risk factor for advanced disease in NAFLD patients. Using International Classification of Diseases, Ninth Revision codes all patients with the diagnosis of T2DM were reviewed and a retrospective chart analysis was performed on 169,910 patients between the ages of 18 to 80. To predict the prevalence of NAFLD, we calculated the hepatic steatosis index. To estimate the prevalence of advanced fibrosis, NAFLD fibrosis score (NFS), fibrosis-4 index, aspartate aminotransferase (AST) to platelet ratio index (APRI), and AST/alanine aminotransferase (ALT) ratio were calculated. Of the 121,513 patients included in the analysis, 89.4% were above normal weight limit. NAFLD based on Hepatic Steatosis Index>36 was present in 87.9% of patients. Advanced fibrosis was present in 35.4% based on NFS>0.676, 8.4% based on fibrosis-4>2.67, 1.9% based on APRI>1.5, and 16.9% based on AST/ALT>1.4% indicating advanced fibrosis and high risk of developing cirrhosis related to NAFLD. In this large cohort of patients with T2DM, we detected high prevalence of hepatic steatosis and advanced fibrosis using noninvasive scores. These scores are easy and nonexpensive tools to screen for NAFLD and advanced fibrosis, although the significant variability of the percentage of patients with advanced fibrosis using these scores indicates the need for further validation in diabetic populations.

Portal and centrilobular hepatic fibrosis in Fontan circulation and clinical outcomes

The Fontan operation redirects venous blood flow directly to the pulmonary circulation in subjects with single ventricle anatomy. Congestive hepatopathy and cirrhosis have been described in subjects with Fontan circulation, but the prevalence of and predictors for liver disease remain unknown. We performed a retrospective study of liver histopathology in Fontan subjects who had liver biopsy or autopsy. All specimens were graded using a pre-determined protocol. Additional data were collected through chart review. Among 68 subjects, specimens were obtained at a median age of 23.2 years (range 5.0 to 52.7 years). Median time since Fontan was 18.1 years (range 1.2 to 32.7 years). Centrilobular fibrosis was seen in every specimen, with 41.2% showing Grade 4 centrilobular fibrosis. Portal fibrosis was seen in 82.3% of specimens, with 14.7% showing cirrhosis. Megamitochondria were seen in 58.8% of specimens. Centrilobular fibrosis grade was greater in those with a dominant left or right ventricle than in those with a combined right and left systemic ventricle (p = 0.008). Portal fibrosis grade correlated with alkaline phosphatase (p = 0.04) and mode of biopsy (p = 0.02). Neither centrilobular fibrosis nor portal fibrosis grade was predictive of transplant-free survival or overall survival. Individuals with Fontan physiology have a high prevalence of hepatic fibrosis. Signs and symptoms of liver disease did not predict histopathologic findings. Few risk factors for advanced disease were identified. Histopathology findings did not predict transplant-free survival. The role of liver biopsy in this population remains uncertain.

The impact of positive soft tissue surgical margins following radical cystectomy for high-grade, invasive bladder cancer

We evaluate the incidence and risk factors associated with positive soft tissue surgical margins (STSM) and determine the association with various surgical and pathological characteristics and clinical outcomes in patients undergoing radical cystectomy (RC) for bladder cancer. From November 1971 to December 2005, 1,591 patients with primary transitional cell carcinoma (TCC) of the bladder underwent RC, with an extended bilateral pelvic lymphadenectomy and urinary diversion. A positive STSM was defined as tumor identified at the inked perivesical soft tissue surrounding the cystectomy specimen. Data were analyzed according to various clinical and pathologic variables, and survival analysis was performed. A total of 18 patients (1%) demonstrated pathologic evidence of a positive STSM following RC. Positive STSM were significantly associated with lymphovascular invasion, advanced pathologic stage, lymph node involvement, extent of nodal involvement and lymph node density. No patient with an organ-confined primary bladder tumor had a positive STSM, while 3% with extravesical tumor extension demonstrated a positive STSM. Recurrence-free and overall survival at 5 and 10 years for patients with a positive STSM was 29 and 22%, and 29 and 11%, respectively (p < 0.001). A positive STSM increased the risk of recurrence by threefold and the overall risk of death by 2.6 times. Only nine patients (1%) without evidence of nodal involvement had a positive STSM with a worse survival compared to those same pathologic subgroup and negative STSM. Nine patients (2%) with lymph node tumor involvement had positive STSM and also demonstrated significantly worse survival. Although a positive STSM was present in only 1% of patients undergoing a RC for TCC of the bladder, it was found to be an independent risk factor for advanced disease, lymph node involvement and tumor progression with worse survival. A dedicated effort should be made to avoid a positive STSM at the time of RC.

Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease

Background:Clinical predictors of advanced non-alcoholic liver disease (NAFLD) are needed to guide diagnostic evaluation and treatment.Methods:To better understand the demographics of NAFLD and risk factors for advanced disease, this study...

A National Sample of Individuals Who Acquired Hepatitis C Virus Infections in Childhood or Adolescence: Risk Factors for Advanced Disease

To describe hepatitis C virus (HCV)-related liver disease in a national cohort of patients who acquired their infections in childhood or adolescence and to assess risk factors for progressive disease and response to antiviral therapy. Demographic, laboratory, and clinical outcome data on 246 individuals who acquired HCV infection before the age of 16 years were extracted from the UK HCV National Register database. Logistic regression analysis was used to investigate the independent effects of sex, age, duration and route of infection, and comorbidity on histological stage of liver disease. Median ages at enrollment and follow-up were 14.0 years (range, 2.2-29.6 years) and 19.2 years (range, 2.3-35.5 years), respectively. Mean duration of infection at enrollment was 8.5 years (standard deviation [SD], 3.3 years), and mean duration of follow-up was 4.5 years (SD, 4.5 years). Fifty-nine (24%) had persistently abnormal liver aminotransferase levels; 22% reported physical signs and symptoms of liver disease. Among 123 individuals with liver biopsies, 117 (95%) had abnormal histological findings. Ninety-eight individuals had biopsies referred for independent blind scoring; median Ishak grade and stage scores were 3 and 1, respectively. Presence of comorbidities (odds ratio [OR], 7.19; 95% CI, 2.00-26.17; P = 0.003) and female sex (OR, 0.31; 95% CI, 0.10-1.00; P = 0.05) were independently associated with histological stage scores greater than the median. A total of 110 individuals received antiviral therapy; 47% achieved a sustained response. HCV-related liver disease in those who acquired the infection in childhood or adolescence was mild for most, although comorbidity and female sex were associated with more advanced disease. Antiviral therapy in childhood or adolescence successfully eradicates the virus for many patients.

Accuracy of EUS Prediction of Disease Extent in Esophageal Cancer (EC) Is Strongly Confounded by Clinical, Endoscopic and Pathologic Factors

Purpose: Confounding is influence of third variables leading to inappropriate estimation of association between test and outcome. EUS is felt to accurately predict disease extent in EC (defined as limited to wall: pTis-T2, pN0 vs. advanced beyond wall: pT3-T4, or pN1). Other available clinical, endoscopic and pathologic (CEP) information is typically ignored, as is its potential confounding effect. Aims: Determine if EUS prediction of disease extent in EC is confounded by CEP information. Methods: 314 pts with EC had clinical evaluation with endoscopy, and EUS, followed by esophagectomy. No pt received preop chemoradiation. Post-op pathology was gold standard. EUS was assessed as a univariable predictor of advanced disease. Next, stepwise logistic regression was used to create a non-EUS 'CEP model' using factors available to any endoscopist (age, gender, weight loss, dysphagia, tumor traversibility, length, location, and morphology, histopathologic type and grade). EUS was then added to the 'CEP model' and its odds ratio recalculated (if CEP factors did not confound EUS prediction of advanced disease, the odds ratio should not change). Results: Pathology at esophagectomy (gold standard): 138 (44%) limited, 176 (56%) advanced. The odds ratio for EUS alone in prediction of advanced disease was 31.4 (i.e. there is 31.4 times greater odds of having advanced disease when EUS predicts it). Non-EUS risk factors for advanced disease (i.e. 'CEP model') were: dysphagia, weight loss, tumor length, and poor histologic grade. When EUS was added to CEP model, its odds ratio fell to 5.64, but remains in final model:TableConclusions: EUS prediction of disease extent is strongly confounded by clinical, endoscopic and pathologic (non-EUS) information, likely because both EUS and non EUS factors strongly predict disease extent. EUS does provide unique information (i.e. stays in final model), but its exact contribution independent of non EUS information is undefined.

Risk factors for advanced disease in colorectal cancer.

The goal of this study was to identify predictors of presenting with late-stage colorectal cancer with a focus on potentially modifiable factors. This was a multicenter, case-based study of patients with colorectal cancer. Detailed information about the cancer was abstracted from the tumor registries, pathology reports, and medical records. The remaining information was obtained by telephone interview. Inclusion criteria were age 40-85 yr with a first diagnosis of histologically proven colorectal cancer between July 1, 1997 and January 1, 2001. Simple contingency table methods were used to examine the relationship between potential risk factors for early versus advanced-stage disease. Logistic regression was performed to simultaneously control for potential confounding factors. There was complete information for 549 respondents. Approximately, 43% of the sample presented with late-stage colorectal cancer. In univariate analysis, lacking a usual source of health care (doctor's office or clinic), no participation in any colorectal cancer screening test in the prior 10 yr, symptoms of blood in stool, and unexplained weight loss were associated with late-stage colorectal cancer. In the logistic regression model, only lacking a usual source of healthcare and unexplained weight loss were associated with late-stage colorectal cancer with odds ratios (95% confidence intervals) of 0.4 (0.2-0.6) and 1.9 (1.2-3.0), respectively. These results suggest that system changes in the VA health-care system that increase access to and improve utilization of primary care may reduce presentation with late-stage colorectal cancer and thus, reduce mortality from colorectal cancer in veterans.

Colorectal cancer: Risk factors for advanced disease

Colorectal cancer: Risk factors for advanced disease

Natural history of hepatitis C in HIV-negative patients with congenital coagulation disorders

Background/Aims: Knowledge of the natural history of hepatitis C is useful for counselling patients and planning treatment. More data are needed from unselected patient groups without concomitant disease. The aim of this study was to describe the natural history of hepatitis C, two decades after infection, in a homogeneous and well-defined group of HIV-negative patients with congenital coagulation defects who had not received specific therapy for chronic hepatitis C. Methods: Medical history, physical examination, laboratory tests and abdominal ultrasonography were performed in 45 HCV-RNA positive, HIV-negative patients, mainly haemophiliacs, from a single centre. Patients were classified according to results of ultrasonography. Results: Two patients had experienced an episode of variceal bleeding; all others were asymptomatic. None had ascites. HCV-RNA titres were >500 000 copies/ml in 23 patients, genotype was 1 in 31 patients. Forty (89%) had elevated transaminases, liver synthesis function was diminished in 7 (16%), and platelet count in 8 (18%). Ultrasonography was normal in 26 (58%) patients, 12 (27%) had isolated splenomegaly, and 7 (16%) had liver nodularity compatible with cirrhosis. Univariate analysis disclosed higher transaminases and γGT, higher age at acquisition of infection and higher present age as risk factors for more advanced disease. Of these, only higher present age was an independent predictor in multivariate analysis. Conclusions: Median 19 years after infection, 58% of patients had no other signs of liver disease than raised transaminases, 16% had cirrhosis on ultrasonography. Only 2/45 patients had symptomatic disease. Higher present age is the main risk factor for advanced disease in this group.