Role of duplex Doppler and power Doppler sonography in transplanted kidneys with acute renal parenchymal dysfunction

The limited work published on the comparison of power Doppler sonography (PDS) and duplex Doppler sonography (DDS) in the assessment of acute renal allograft dysfunction has shown contradictory results. We compared the role of DDS and PDS in renal transplant recipients developing acute renal parenchymal dysfunction and correlated these findings with kidney biopsy, which was taken as the gold standard. Thirty post-renal transplant patients with acute graft dysfunction underwent Doppler sonography, DDS and PDS using an HDI 5000 ATL machine. Patients who developed graft dysfunction as a result of vascular, obstructive or other non-parenchymal causes were excluded. All patients underwent an allograft biopsy within 72 h of the sonography. Based on the biopsy findings, 24 patients were categorized as having acute rejection, and six patients as having no rejection. The overall sensitivity, specificity and accuracy of DDS for evaluation of graft dysfunction were 54.17, 33.33, and 50.00%, respectively, and that for PDS were superior with 87.50, 33.30, and 76.67%, respectively. The low specificity can be partially attributed to the small number of cases without rejection in our study population. We conclude that PDS is superior to DDS in screening patients with acute parenchymal renal dysfunction post-transplant. However, a normal PDS examination does not exclude the presence of acute rejection. Power Doppler sonography is a useful screening test for diagnosing acute rejection but a renal allograft biopsy remains the gold standard for diagnosis of this condition.     

Use of non‐steroidal anti‐inflammatory drugs and risk of non‐Hodgkin lymphoma: a systematic review and meta‐analysis

Epidemiological study findings regarding the association between use of non‐steroidal anti‐inflammatory drugs (NSAIDs) and risk of non‐Hodgkin lymphoma (NHL) have been inconsistent. We aimed to systematically review epidemiological studies of the association and calculate pooled relative risks using meta‐analytic methods. We searched eight electronic literature databases and three clinical trial registers to identify all studies (including observational studies and randomized clinical trials) of the association published prior to October 2013. Identified studies were independently reviewed by two researchers. We used a random effects model to calculate pooled odds ratio (PORs). Heterogeneity amongst studies was examined using Cochran's Q and I‐squared (I²) tests; and sources of heterogeneity were explored using subgroup and meta‐regression analyses. A total of 17 studies (12 case‐control studies and five cohort studies), all adult studies, were included. Use of NSAIDs was not associated with overall risk of NHL [POR = 1.05, and 95% confidence interval (95% CI) 0.90–1.22] or NHL subtypes including B‐cell lymphoma, T‐cell lymphoma, follicular lymphoma, diffuse large B‐cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Aspirin use was associated with reduced risk of CLL/SLL (POR = 0.70, 95% CI 0.54–0.91) but not with the risk of all NHLs (POR = 1.02, 95% CI 0.89–1.17). Use of non‐aspirin NSAIDs was associated with increased risk of NHL (POR = 1.41, 95% CI 1.01–1.97) amongst females only. The epidemiologic evidence remains inconclusive. Effects of NSAIDs may differ by drug type, NHL subtype, and sex and more studies taking into consideration these differences are needed. Copyright © 2014 John Wiley & Sons, Ltd.     

Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma: Possible association with non‐B non‐C hepatitis pathogenesis

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD⁺)‐dependent protein deacetylase. In mice, mSirt1 deficiency causes the onset of fatty liver via regulation of the hepatic nutrient metabolism pathway. In this study, we demonstrate SIRT1 expression, activity and NAD⁺ regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non‐B non‐C (NBNC) hepatitis. SIRT1 expression levels were higher in NBNC patients than in healthy donors, while SIRT1 histone H3K9 deacetylation activity was suppressed in NBNC patients. In the liver of hepatitis patients, decreased NAD⁺ amounts and its regulatory enzyme nicotinamide phosphoribosyltransferase expression levels were observed, and this led to inhibition of SIRT1 activity. SIRT1 expression was associated with HIF1 protein accumulation in both the NBNC liver and liver cancer cell lines. These results may indicate that the NBNC hepatitis liver is exposed to hypoxic conditions. In HepG2 cells, hypoxia induced inflammatory chemokines, such as CXCL10 and MCP‐1. These inductions were suppressed in rich NAD⁺ condition, and by SIRT1 activator treatment. In conclusion, hepatic SIRT1 activity was repressed in NBNC patients, and normalization of NAD⁺ amounts and activation of SIRT1 could improve the inflammatory condition in the liver of NBNC hepatitis patients.     

Association of total cholesterol,low‐density lipoprotein cholesterol,and non‐high‐density lipoprotein cholesterol with atherosclerotic cardiovascular disease and cancer in a Chinese male population

This prospective study included 68,759 Chinese male adults from Kailuan cohort of China who had a standardized medical examination between 2006 and 2007 and were followed up for approximately 8 years until occurrence of ASCVD, cancer or death or until December 31, 2014. Subjects were divided into four categories based on the quartiles of TC, LDL‐C and non‐HDL‐C. Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs). During follow‐up, 2,916 males developed ASCVD and 1,884 developed cancer. Compared with the lowest quartile, the upper‐most quartiles of TC, LDL‐C and non‐HDL‐C were all associated with increased ASCVD risk (HR 1.53; HR 1.16; HR 1.55); however, the upper‐most quartiles of TC, LDL‐C and non‐HDL‐C were all negatively associated with cancer (HR0.84; HR 0.82; HR 0.80) and these associations were present after exclusion of incident cancers during the first 4 years of follow‐up. In a word, we report that high TC, LDL‐C and non‐HDL‐C concentrations increased ASCVD incidence in a male population and that these lipid profiles were inversely associated with total cancer and several individual cancers.     

Bevacizumab for non‐small‐cell lung cancer: A nested case control study of risk factors for hemoptysis

Potentially life‐threatening, serious hemoptysis is an adverse event associated with bevacizumab in non‐squamous non‐small‐cell lung cancer (NSCLC) trials. Suggested risk factors include central tumor location and cavitation; however, the profile of hemoptysis occurrence in clinical practice is still unclear. A nested case‐control study was conducted to assess the onset profile and risk factors for hemoptysis in bevacizumab‐treated patients in a real‐world setting in Japan. After bevacizumab was approved for NSCLC, physicians registered all NSCLC patients scheduled for bevacizumab therapy, from November 2009 to August 2011. Patients developing grade 2 hemoptysis requiring an injectable hemostatic agent or grade ≥3 hemoptysis were selected as case subjects, matched with four control subjects each. Case report forms were collected after an observation period of 24 weeks. Radiologists assessed blinded thoracic images. Risk factors for hemoptysis were assessed by univariate and stepwise multivariate analysis. Of 6774 patients registered, 23 (0.3%) experienced grade ≥2 drug‐related hemoptysis. A total of 104 patients (21 cases, 83 controls) were analyzed by central reviewers for risk factors of hemoptysis occurrence. In the univariate analysis seven factors were associated with hemoptysis. In the step‐wise multivariate analysis, prior thoracic radiotherapy (P = 0.1844), presence of tumor exposure in the central airway (P = 0.0256) and concomitant radiotherapy (P = 0.1169) were identified as risk factors for hemoptysis. While the incidence of hemoptysis was low in the real‐world setting in Japan, the three risk factors identified, prior thoracic radiotherapy, presence of tumor exposure in the central airway and concomitant radiotherapy, should be considered when selecting patients for bevacizumab treatment. Although technically classed as a clinical trial, a nested case‐control study was a non‐interventional surveillance study analyzing all NSCLC patients receiving bevacizumab in Japan, therefore it was not registered as a phase II/III clinical trial would be.     

An evaluation of lower‐body functional limitations among long‐term survivors of 11 different types of cancers

BACKGROUND:

The authors examined potential reasons (sociodemographics, psychologic distress, health behavior, chronic health conditions, access to medical care) for increased prevalence of lower‐body functional limitations among long‐term (≥5 years) cancer survivors.

METHODS:

The authors used National Health Interview Survey data from 2005 through 2007, and defined lower‐body functional limitation as reporting difficulty/inability to perform at least 1 of 5 activities (walking approximately one–quarter of a mile; walking up and down 10 steps without rest; standing for 2 hours; stooping, crouching, or kneeling; and lifting 10 lbs). Increased prevalence of lower‐body functional limitations was compared between long‐term survivors of each of 11 cancer types reported by ≥50 respondents (n = 2143) and persons without cancer history (controls; n = 72,618).

RESULTS:

Among cancer survivors, 57.0% had a lower‐body functional limitation versus 26.6% of controls. The unadjusted prevalence of lower‐body functional limitations varied by cancer type, ranging from 44.9% (lymphoma survivors) to 88.8% (lung cancer survivors). Long‐term lung (odds ratio [OR], 7.91), uterine (OR, 2.41), thyroid (OR, 2.27), cervical (OR, 1.76), ovarian (OR, 1.75), and breast (OR, 1.35) cancer survivors had increased odds of reporting a lower‐body functional limitation than controls after adjusting for sociodemographic factors (all P < .05). Differences in the prevalence of arthritis and lower‐back pain and in access to medical care explained differences in lower‐body functional limitation prevalence between controls and long‐term breast, cervical, ovarian, and uterine cancer survivors. Long‐term bladder, colorectal, lymphoma, melanoma, and prostate cancer survivors were equally likely to report a lower‐body functional limitation as controls.

CONCLUSIONS:

Treatment of arthritis and lower–back pain and increasing access to medical care might help reduce the risk of lower‐body functional limitations and improve quality of life among specific long‐term cancer survivors. Cancer 2009. © 2009 American Cancer Society.     

Comparison of gefitinib,erlotinib and afatinib in non‐small cell lung cancer: A meta‐analysis

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non‐small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta‐analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression‐free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first‐line treatment of EGFR‐mutant NSCLC. However, afatinib was more effective than erlotinib as second‐line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.     

Fruits and vegetables consumption and risk of non‐Hodgkin's lymphoma: A meta‐analysis of observational studies

Epidemiologic evidence suggests that intakes of fruits and/or vegetables may play a role in the etiology of non‐Hodgkin's lymphoma (NHL), but the findings are inconsistent. We aimed to assess fruits and/or vegetables intakes in relation to risk of NHL by a meta‐analytic approach. We searched on PubMed database from January 1966 to September 2012 to indentify case‐control and cohort studies. We used a random‐effects model to compute summary risk estimates. For vegetables, the summary relative risks (RRs) of NHL for high versus low intake for case‐control, cohort and all studies were 0.75 (95% CI, 0.60–0.94; N = 8), 0.90 (95% CI, 0.81–1.00; N = 5) and 0.81 (95%CI, 0.71–0.92; N = 13) ; and the corresponding RRs for intake of 1 serving per day were 0.88 (95% CI, 0.80–0.96; N = 8), 0.96 (95% CI, 0.92–1.00; N = 5) and 0.92 (95%CI, 0.87–0.96; N = 13). For fruits and vegetables combined, the summary RR for high versus low intake was 0.78 (95%CI, 0.66–0.92; N = 4), and for intake of 1 serving per day was 0.95 (95%CI, 0.91–1.00; N = 4). Regarding histological subtypes, vegetables intake was significantly inversely associated with diffuse large B‐cell lymphoma and follicular lymphoma, but not small lymphocytic lymphoma/chronic lymphocytic leukemia (high vs. low intake, RR = 0.70, 0.70 and 1.01, respectively; N = 7, 7 and 10, respectively). Fruits intake was generally not associated with total NHL, or any histological subtypes. Our findings suggest that intakes of vegetables, and fruits and vegetables combined, but not fruits alone, significantly reduce risk of NHL.     

Relationship between response rates and median progression‐free survival in non‐Hodgkin's lymphoma: A meta‐analysis of published clinical trials

Demonstration of clinical effectiveness of a non‐Hodgkin's lymphoma (NHL) treatment generally involves determination of progression‐free survival (PFS). However, the long evaluation time of PFS limits its utility to make timely decisions in drug development. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in NHL. A database was systematically developed from 513 identified NHL trials reported from 1996 to 2015. Potential predictors of the relationship between response rates and PFS were evaluated, including age, sex, treatment, percentage of treatment‐naïve patients, and subtype of NHL. Seventy‐three trials involving 86 cohorts were included in the meta‐analysis. Linear regression analysis using logit of response rates and logarithm of median PFS indicated that the correlation between overall response rate (ORR) and median PFS was higher (R² = 0.70) when compared to that of complete response (CR) rate and median PFS (R² = 0.57). Furthermore, the correlation was improved with the addition of percentage of treatment‐naïve patients and percentage of patients with follicular lymphoma (FL) (P < .005) between ORR and median PFS (R² = 0.78), and between CR rate and median PFS relationship (R² = 0.74). Treatment was not found to alter this relationship. In summary, ORR is as good as CR rate in predicting median PFS. Moreover, longer median PFS is expected in the trials including treatment‐naïve and/or FL patients at a given ORR/CR rate. The determined relationship can be used to project the median PFS based on ORR or CR rate.     

Patterns of care for non‐small cell lung cancer patients in Belgium: A population‐based study

Guidelines recommend surgery for Stage I‐II, chemoradiation for Stage III and systemic therapy for Stage IV non‐small cell lung cancer (NSCLC). However, patient related factors and patient preferences influence treatment decisions. We investigated patterns of care for Belgian NSCLC patients in 2010‐2011, based on population‐based data from the Belgian Cancer Registry and administrative databases. The relationship between patient characteristics, institutional diagnostic volume, type of treatment and survival was investigated. Overall, 20.8% of patients received no oncological treatment. 59% and 22.1% of Stage I‐II patients received primary surgery or (chemo)radiation respectively. 34% of Stage III patients received chemoradiation and 17% of Stage IIIA patients had surgery. 70% of Stage IV patients received chemotherapy or targeted therapy. Moderate variability between centres was observed. For Stage IV, systemic therapy was less frequently used in higher volume centres and 1‐year survival was lower in centres that had ≥ 50 new patients yearly. Although not all NSCLC patients received treatment as ideally recommended by guidelines, these results do not necessarily represent poor quality of care as patient characteristics and preferences need to be taken into account. Treatment options targeted towards patients with co‐morbidity or unfit patients is warranted to improve outcomes of all NSCLC patients.     

Relationship between ambient ultraviolet radiation and non‐Hodgkin lymphoma subtypes: A U.S. population‐based study of racial and ethnic groups

Associations between ultraviolet radiation (UVR) exposure and non‐Hodgkin lymphoma (NHL) have been inconsistent, but few studies have examined these associations for specific subtypes or across race/ethnicities. We evaluated the relationship between ambient UVR exposure and subtype‐specific NHL incidence for whites, Hispanics and blacks in the United States for years 2001–2010 (n = 187,778 cases). Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for UVR quintiles using Poisson regression. Incidence was lower for the highest UVR quintile for chronic/small lymphocytic/leukemia (CLL/SLL) (IRR = 0.87, 95% CI: 0.77–0.97), mantle cell (IRR = 0.82, 95% CI: 0.69–0.97), lymphoplasmacytic (IRR = 0.58, 95% CI: 0.42–0.80), mucosa‐associated lymphoid tissue (MZLMALT) (IRR = 0.74, 95% CI: 0.60–0.90), follicular (FL) (IRR = 0.76, 95% CI: 0.68–0.86), diffuse large B‐cell (IRR = 0.84, 95% CI: 0.76–0.94;), peripheral T‐cell other (PTCL) (IRR = 0.76, 95% CI: 0.61–0.95) and PTCL not otherwise specified (PNOS) (IRR = 0.77, 95% CI: 0.61–0.98). Trends were significant for MZLMALT, FL, DLBCL, BNOS and PTCL, with FL and DLBCL still significant after Bonferroni correction. We found interaction by race/ethnicity for CLL/SLL, FL, Burkitt, PNOS and MF/SS, with CLL/SLL and FL still significant after Bonferroni correction. Some B‐cell lymphomas (CLL/SLL, FL and Burkitt) suggested significant inverse relationships in whites and Hispanics, but not in blacks. Some T‐cell lymphomas suggested the most reduced risk for the highest quintile of UVR among blacks (PNOS and MF/SS), though trends were not significant. These findings strengthen the case for an inverse association of UVR exposure, support modest heterogeneity between NHL subtypes and suggest some differences by race/ethnicity.     

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

Because of high specificity and easy detection in the tissues, serum, plasma, urine and saliva, interest in exploring the potential of long non‐coding RNAs (lncRNAs) in cancer patients continues to increase. LncRNAs have shown potential as a biomarker in the diagnosis and prognosis of bladder cancer, prostate cancer, gastric cancer, pancreatic cancer, breast cancer and many other cancer types. Some lncRNAs have also been used as adjunct to improve the specificity and sensitivity of existing biomarkers. The molecular tools such as RNA‐seq, RNA‐FISH, ic‐SHAPE and quantitative real‐time PCR have been used for examining the lncRNAs' potential. Some lncRNAs such as PCA3 is now routinely used in the clinic for the diagnosis of prostate cancer. Single nucleotide polymorphisms (SNPs) in lncRNAs can also be used as a predictor of cancer risk. Although ongoing studies continue to unravel the underlying mechanism, some lncRNAs have been used as therapeutic targets for the selective killing of cancer cells in patients. Thus lncRNAs are emerging as convenient and minimally invasive diagnostic/prognostic markers, and also as therapeutic target. Companies such as the Curna Inc., MiNA Therapeutics Ltd. and RaNA Therapeutics Inc. have been taking steps to develop lncRNA based strategies against cancer. In this review, we discuss the potential of lncRNAs as biomarkers and therapeutic targets in cancer patients.     

Lifetime alcohol intake and risk of non‐Hodgkin lymphoma: Findings from the Melbourne Collaborative Cohort Study

Cohort studies have reported inconsistent evidence regarding alcohol intake and risk of non‐Hodgkin lymphoma (NHL), mostly based on alcohol intake assessed close to study enrolment. We examined this association using alcohol intake measured from age 20 onwards. We calculated usual alcohol intake for 10‐year periods from age 20 using recalled frequency and quantity of beverage‐specific consumption for 37,990 participants aged 40–69 years from the Melbourne Collaborative Cohort Study. Cox regression was performed to derive hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between alcohol intake (g/day) and NHL risk. After a mean follow‐up of 19.3 years, 538 NHL cases were diagnosed. Approximately 80% of participants were either lifetime abstainers or consumed below 20 g of ethanol/day. All categories of lifetime alcohol intake were associated with about 20% lower incidence of NHL compared with lifetime abstention, but there was no evidence of a trend by amount consumed (HR = 0.97 per 10 g/day increment in intake, 95% CI: 0.92–1.03; p value = 0.3). HRs for beer, wine and spirits were 0.91 (95% CI: 0.83–1.00; p value = 0.05), 1.03 (95% CI: 0.94–1.12; p value = 0.6), and 1.06 (95% CI: 0.83–1.37; p value = 0.6), respectively, per 10 g/day increment in lifetime intake. There were no significant differences in associations between NHL subtypes. In this low‐drinking cohort, we did not detect a dose‐dependent association between lifetime alcohol intake and NHL risk.     

Treatment non‐adherence in teenage and young adult cancer patients: a preliminary study of patient perceptions

Objectives: Non‐adherence (NA) by adolescents receiving cancer treatment is believed to be a major problem. However, adequate measures of NA have not been developed. The purpose of this study was to (1) assess the internal reliability of a new scale reflecting low‐risk NA behaviours, (2) examine whether the scores on this scale were associated with high‐risk NA behaviours and (3) assess the relationship between NA behaviours and patient attitudes towards stopping treatment. Methods: Thirty‐three patients (16–24 years) with solid tumours reported on their previous adherence with treatment. Low‐risk NA behaviours were assessed on a 0–40 scale derived from the sum of 10 items. High‐risk NA behaviours and attitudes towards stopping treatment were assessed by questions with yes/no response options. Results: Internal reliability of the low‐risk NA scale was α=0.73. Patients not seeking help for pyrexia had higher total low‐risk NA scores than those who sought help (mean 7.4, SD 5.3 vs mean 3.5, SD 3.6, t=2.1, p=0.03). There was also a trend for individuals who ignored pyrexia to be more likely to have contemplated stopping treatment than those who sought medical assistance (Fisher's Exact=0.09). Conclusions: A scale reflecting low‐risk NA behaviour had good internal reliability and was associated with not seeking help when pyrexic. Ignoring a temperature was also associated with contemplating stopping treatment. We are now conducting a prospective study using the measure to assess validity against a range of information regarding NA. Copyright © 2009 John Wiley & Sons, Ltd.