Identification of Circulating MicroRNAs as Novel Potential Biomarkers for Gastric Cancer Detection: A Systematic Review and Meta-Analysis

Background

Recent studies show that microRNAs (miRNAs) in serum or plasma can be stably detected and used as potential biomarkers in cancer diagnosis.

Objectives

To systematically evaluate circulating miRNAs from numerous gastric cancer (GC) expression profiling studies and to determine miRNA biomarkers for GC detection.

Methods

A systematic review and meta-analysis of published studies comparing the circulating miRNA expressions between GC patients and healthy controls were carried out. An miRNA ranking system that considered the number of comparisons in agreement, total number of samples, and average fold change was used. Then the receiver-operating characteristic curve (ROC) results of the top miRNAs were combined to further evaluate their diagnostic value by using Meta-disc 1.4.

Results

A total of 35 miRNAs were reported in the 22 included studies, with 7 miRNAs reported in at least 2 studies. MiR-21 is the most consistently reported miRNA with upregulation. In further analysis, the sensitivity, specificity, and area under the curve of summary ROC for miR-21 in GC diagnosis are 0.78 (95 % CI 0.71–0.85), 0.89 (95 % CI 0.82–0.94), and 0.91, respectively.

Conclusion

Circulating miR-21 can serve as a potential biomarker for detection of GC.     

Molecular determinants of outcome in sorafenib-treated patients with hepatocellular carcinoma

Purpose

Preclinical studies show that sorafenib, a multitarget kinase inhibitor, displays anti-proliferative, anti-angiogenic, and pro-apoptotic properties in hepatocellular carcinoma (HCC). However, the determinants of sorafenib sensitivity in vivo remain largely unknown.

Methods

We assessed the expression of Mcl-1, activated/phosphorylated extracellular signal-regulated kinase (pERK) 1/2, and activated/phosphorylated AKT (pAKT) in pretreatment tumor specimens from 44 patients with advanced HCC who received sorafenib. Furthermore, we assessed MYC and MET gene copy numbers (GCN) by fluorescence in situ hybridization.

Results

Poorer overall survival (OS) times were correlated with pERK expression [hazard ratio (HR) 1.013; 95 % CI 1.003–1.035] and Mcl-1 expression (HR 1.016; 95 % CI 1.002–1.030) in pretreatment tumor samples. Expression levels of pERK and Mcl-1, however, were not correlated with time to tumor progression (TTP). Increased pERK expression was positively associated with higher Cancer of Liver Italian Program scores (P = 0.012) and was prognostic in patients with scores 2–6 but not in those with scores 0–1. pERK expression was significantly less frequent in specimens sourced from previous surgical procedures compared to biopsy samples (9.6 vs. 92.3 %, respectively; P < 0.0001). Analysis of pAKT expression, MET and MYC GCN, did not indicate any prognostic nor predictive values for these biomarkers in terms of survival.

Conclusions

Expression levels of Mcl-1 and pERK are associated with reduced OS in HCC patients treated with sorafenib and might be useful markers for risk stratification. However, in contrast to previous findings, pERK expression levels, as well as other biomarkers tested, did not affect TTP.     

Decreasing Disparities in Breast Cancer Screening in Refugee Women Using Culturally Tailored Patient Navigation

BACKGROUND

Patient navigator (PN) programs can improve breast cancer screening in low income, ethnic/racial minorities. Refugee women have low breast cancer screening rates, but it has not been shown that PN is similarly effective.

OBJECTIVE

Evaluate whether a PN program for refugee women decreases disparities in breast cancer screening.

DESIGN

Retrospective program evaluation of an implemented intervention.

PARTICIPANTS

Women who self-identified as speaking Somali, Arabic, or Serbo-Croatian (Bosnian) and were eligible for breast cancer screening at an urban community health center (HC). Comparison groups were English-speaking and Spanish-speaking women eligible for breast cancer screening in the same HC.

INTERVENTION

Patient navigators educated women about breast cancer screening, explored barriers to screening, and tailored interventions individually to help complete screening.

MAIN MEASURES

Adjusted 2-year mammography rates from logistic regression models for each calendar year accounting for clustering by primary care physician. Rates in refugee women were compared to English-speaking and Spanish-speaking women in the year before implementation of the PN program and over its first 3 years.

RESULTS

There were 188 refugee (36 Somali, 48 Arabic, 104 Serbo-Croatian speaking), 2,072 English-speaking, and 2,014 Spanish-speaking women eligible for breast cancer screening over the 4-year study period. In the year prior to implementation of the program, adjusted mammography rates were lower among refugee women (64.1 %, 95 % CI: 49–77 %) compared to English-speaking (76.5 %, 95 % CI: 69 %–83 %) and Spanish-speaking (85.2 %, 95 % CI: 79 %–90 %) women. By the end of 2011, screening rates increased in refugee women (81.2 %, 95 % CI: 72 %–88 %), and were similar to the rates in English-speaking (80.0 %, 95 % CI: 73 %–86 %) and Spanish-speaking (87.6 %, 95 % CI: 82 %–91 %) women. PN increased screening rates in both younger and older refugee women.

CONCLUSION

Linguistically and culturally tailored PN decreased disparities over time in breast cancer screening among female refugees from Somalia, the Middle East and Bosnia.     

Association study identifying polymorphisms in CD47 and other extracellular matrix pathway genes as putative prognostic markers for colorectal cancer

Purpose

We identified recently the extracellular matrix (ECM) receptor interaction pathway as a consistently overrepresented category among gene expression profiling studies on colorectal cancer (CRC) prognosis.

Methods

Putative regulatory single nucleotide polymorphisms (SNPs) in genes from the ECM pathway were genotyped in 613 CRC patients from Northern Germany (PopGen cohort) and tested for association with disease progression and survival.

Results

The eSNP (SNP associated with expression) rs12695175 in CD47 associated with CRC specific survival (HR?=?2.18, 95 % CI 1.10–4.33, CC versus AA) and with overall survival (HR?=?1.99, 95 % CI 1.04–3.81, CC versus AA). This association remained significant after adjustment for age at diagnosis, tumour stage (T) and lymph node status (N). Three polymorphisms in CD47 were associated with distant metastasis in a dominant model: rs9879947 and rs3206652 in the 3′-UTR (OR?=?1.64, 95 % CI 1.01–2.64 and OR?=?1.88, 95 % CI 1.27–2.80, respectively) and the eSNP rs3804639 (OR?=?1.73, 95 % CI 1.17–2.57).

Conclusions

The novel associations of eSNPs in CD47 with worse survival and distant metastasis should be confirmed by additional studies, since increased expression of this gene has recently been shown to be an indicator of poor prognosis in cancer patients.     

Diagnostic accuracy of urinary dipstick to exclude catheter-associated urinary tract infection in ICU patients: a reappraisal

Objectives

We wanted to assess the diagnostic accuracy of urinary dipstick testing in excluding catheter-associated urinary tract infection (CAUTI) in intensive care unit (ICU) patients with fever or hypothermia.

Methods

This was a prospective observational cohort study in a medical-surgical ICU. Patients with new-onset fever >38.3 °C or hypothermia <36 °C at least 48 h after urinary catheter insertion were included over a 2-year period. At each episode, a urinary dipstick test and a urine culture were performed as the criterion standard. Extensive microbiological investigations for extra-urinary infections were performed also. The performances of various urinary dipstick result combinations in ruling out CAUTI were compared based on the likelihood ratios (LR+ and LR?).

Results

Symptomatic CAUTI was diagnosed in 31 (24.4 %) of the 127 included patients (195 episodes of fever or hypothermia). LR+ was best for combined leukocyte esterase-positive and nitrite-positive dipstick results (overall population: 14.91; 95 % confidence interval [95 % CI], 5.53–40.19; patients without urinary symptoms: 15.63; 95 % CI, 5.76–42.39). LR? was best for either leukocyte esterase-positive or nitrite-positive dipstick results (overall population: 0.41; 95 % CI, 0.57–0.65; patients without urinary symptoms, 0.36; 95 % CI, 0.21–0.60).

Conclusions

Urinary dipstick testing at the bedside does not help to rule out symptomatic CAUTI in medical or surgical ICU patients with fever or hypothermia.     

The prognostic role of matrix metalloproteinase 2 in gastric cancer: a systematic review with meta-analysis

Purpose

The prognostic role of matrix metalloproteinase 2 (MMP-2) in gastric cancer remains controversial. We systematically reviewed the evidence for assessment of MMP-2 expression in gastric cancer to elucidate this issue.

Method

Pubmed, Embase and Web of Science were searched to identify eligible studies to evaluate the association of MMP-2 expression and overall survival and clinicopathological features of gastric cancer.

Results

MMP-2 overexpression was significantly correlated with poor OS of gastric cancer patients (HR 1.92, 95 % CI 1.48–2.48). Subgroup analysis indicated that MMP-2 overexpression had an unfavorable impact on OS in Asian countries (HR 2.23, 95 % CI 1.57–3.17) and European countries (HR 1.43, 95 % CI 1.13–1.80). Furthermore, MMP-2 overexpression was significantly associated with TNM stage (TIII/TIV vs TI/TII: OR 2.17, 95 % CI 1.64–2.87), the depth of invasion (T3/T4 vs T1/T2: OR 2.59, 95 % CI 1.63–4.12), lymph node metastasis (positive vs negative: OR 2.21, 95 % CI 1.69–2.88), and distant metastasis (positive vs negative: OR 4.44, 95 % CI 1.24–15.94).

Conclusion

This meta-analysis indicated that MMP-2 overexpression might be a predictive factor for poor prognosis for gastric cancer.     

A comparison of glypican-3 with alpha-fetoprotein as a serum marker for hepatocellular carcinoma: a meta-analysis

Backgrounds

Glypican-3(GPC3) has been reported as one of the most promising serum markers for hepatocellular carcinoma (HCC), while several studies have conflicting results for the diagnostic accuracy between GPC3 and alpha-fetoprotein (AFP).

Methods

Studies that explored the diagnostic value of GPC3 and AFP in HCC were searched in MEDLINE, EMBASE, PUBMED, the Cochrane Library and Chinese biomedical literature database (CBM). Sensitivity, specificity and other measures about the accuracy of serum GPC3 and AFP in the diagnosis of HCC were pooled using random effects models. Summary receiver operating characteristic curve (sROC) analysis was used to summarize the overall test performance.

Results

Ten studies were included in our meta-analysis. The pooled sensitivity for AFP and GPC3 is 51.9 % (95 % confidence interval (CI) 0.47–0.56) and 59.2 % (95 % CI 0.55–0.63), respectively, while the pooled specificity for AFP and GPC3 is 94 % (95 % CI 92.1–95.6 %) and 84.8 % (95 % CI 82–87.3 %), respectively. The pooled diagnostic odds ratio (DOR) for AFP and GPC3 were 23.4 (95 % CI 10.3–53.2) and 17.99 (95 % CI 5.4–60.4), respectively. Area under sROC for both AFP and GPC3 is 0.81 (95 % CI 0.77–0.84).

Conclusions

GPC3 is comparable to AFP as a serum marker for the diagnosis of HCC, combination of AFP and GPC3 can elevate the sensitivity of diagnosis.     

Diagnostic accuracy of EUS and CT of vascular invasion in pancreatic cancer: a systematic review

Objective

The objective of this study was to summarize the accuracy of preoperative vascular invasion with endoscopic ultrasound (EUS) and computed tomography (CT) test performance in pancreatic cancer with meta-analysis

Method

Two reviewers searched MEDLINE database to identify relevant studies. The reference lists of the trials were manually searched. Included studies used surgical and/or histological findings as the “gold standard,” and provided sufficient data to construct a diagnostic 2 × 2 table. A statistical program of Meta-Disc was used to calculate the pooled sensitivity, specificity, positive LR, negative LR, DOR, and the SROC curve. Publication bias was assessed by Deeks’ asymmetry test. Sensitivity analysis and subgroup analysis were calculated to down the heterogeneity. Meta-regression was calculated to evaluate potential sources of heterogeneity

Result

A total of 30 studies with 1,554 patients were included for the analysis, nine of these studies compared EUS with CT to assess the diagnostic efficiency The pooled sensitivity of EUS and CT was 72 % (95 % CI 67–77 %) and 63 % (95 % CI 58–67 %), and the pooled specificity of EUS and CT was 89 % (95 % CI 86–92 %) and 92 % (95 % CI 90–94 %), respectively. The positive LR of EUS and CT was 5.14 (95 % CI 3.14–8.40) and 6.21 (95 % CI 3.96–9.71), and the negative LR was 0.36 (95 % CI 0.25–0.52) and 0.41 (95 % CI 0.31–0.55), respectively. The AUCs of EUS and CT were 0.9037 and 0.8948. The subgroup analysis of nine studies performed both EUS and CT showed CT scan with a lower sensitivity of 48 % (95 % CI 0.40–0.56), when compared to EUS of 69 % (95 % CI 0.61–0.77). The overall AUCs of CT scan appear to be lower (AUCs = 0.8589), compared with EUS (AUCs = 0.9379)

Conclusion

EUS performed better than CT in differentiating vascular invasion preoperative on pancreatic cancer. EUS could provide other additional information when compared with CT.     

Polypharmacy and Risk of Antiretroviral Drug Interactions Among the Aging HIV-Infected Population

BACKGROUND

Among aging HIV-infected adults, polypharmacy and its consequences have not been well-described.

OBJECTIVE

To characterize the extent of polypharmacy and the risk of antiretroviral (ARV) drug interactions among persons of different ages.

DESIGN AND PARTICIPANTS

Cross-sectional analysis among patients within the HIV Outpatient Study (HOPS) cohort who were prescribed ARVs during 2006–2010.

MAIN MEASURES

We used the University of Liverpool HIV drug interactions database to identify ARV/non-ARV interactions with potential for clinical significance.

KEY RESULTS

Of 3,810 patients analyzed (median age 46 years, 34 % ≥ 50 years old) at midpoint of observation, 1,494 (39 %) patients were prescribed ≥ 5 non-ARV medications: 706 (54 %) of 1,312 patients ≥ 50 years old compared with 788 (32 %) of 2,498 patients < 50 years. During the five-year period, the number of patients who were prescribed at least one ARV/non-ARV combination that was contraindicated or had moderate or high evidence of interaction was 267 (7 %) and 1,267 (33 %), respectively. Variables independently associated with having been prescribed a contraindicated ARV/non-ARV combination included older age (adjusted odds ratio [aOR] per 10 years of age 1.17, 95 % CI 1.01–1.35), anxiety (aOR 1.78, 95 % CI 1.32–2.40), dyslipidemia (aOR 1.96, 95 % CI 1.28–2.99), higher daily non-ARV medication burden (aOR 1.13, 95 % CI 1.10–1.17), and having been prescribed a protease inhibitor (aOR 2.10, 95 % CI 1.59–2.76). Compared with patients < 50 years, older patients were more likely to have been prescribed an ARV/non-ARV combination that was contraindicated (unadjusted OR 1.44, 95 % CI 1.14–1.82), or had moderate or high evidence of interaction (unadjusted OR 1.29, 95 % CI 1.15–1.44).

CONCLUSIONS

A substantial percentage of patients were prescribed at least one ARV/non-ARV combination that was contraindicated or had potential for a clinically significant interaction. As HIV-infected patients age and experience multiple comorbidities, systematic reviews of current medications by providers may reduce risk of such exposures.     

Use of FDG-PET or PET/CT to detect recurrent colorectal cancer in patients with elevated CEA: a systematic review and meta-analysis

Aim

The purpose of the present study was to conduct a systematic review and meta-analysis of the published literature to assess the diagnostic performance of FDG-PET or PET/CT in the detection of recurrent colorectal cancer (CRC) rising in patients with elevated CEA.

Materials and methods

The authors conducted a systematic MEDLINE search of published articles. Two reviewers independently assessed the methodological quality of each study. We estimated pooled sensitivity and specificity and positive and negative likelihood ratios, and summary receiver-operating characteristic curves in the detection of recurrent CRC in patients with elevated CEA.

Results

Eleven studies with a total of 510 patients met the inclusion criteria. One hundred and six patients (106/510?=?20.8 %) had true-negative FDG-PET (PET/CT) results in detection of recurrent CRC when rising CEA. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET in the detection of tumor recurrence in CRC patients with elevated CEA were 90.3 % (95 % CI, 85.5–94.0 %), 80.0 % (95 % CI, 67.0–89.6 %), 2.88 (95 % CI, 1.37–6.07), and 0.12 (95 % CI, 0.07–0.20), respectively. The pooled estimates of sensitivity and specificity and positive and negative likelihood ratios of FDG-PET/CT in the detection of tumor recurrence in CRC patients with elevated CEA were 94.1 % (95 % CI, 89.4–97.1 %), 77.2 % (95 % CI, 66.4–85.9 %), 4.70 (95 % CI, 0.82–12.13), and 0.06 (95 % CI, 0.03–0.13), respectively.

Conclusions

Whole-body FDG-PET and PET/CT are valuable imaging tools for the assessment of patients with suspected CRC tumor recurrence based on the increase of CEA.     

The Impact of Financial Barriers on Access to Care, Quality of Care and Vascular Morbidity Among Patients with Diabetes and Coronary Heart Disease

BACKGROUND

The prevalence and consequences of financial barriers to health care among patients with multiple chronic diseases are poorly understood.

OBJECTIVE

We sought to assess the prevalence of self-reported financial barriers to health care among individuals with diabetes and coronary heart disease (CHD) and to determine their association with access to care, quality of care and clinical outcomes.

DESIGN

The 2007 Centers for Disease Control Behavioral Risk Factor Surveillance Survey.

PARTICIPANTS

Diabetic patients with CHD.

MAIN MEASURES

Financial barriers to health care were defined by a self-reported time in the past 12 months when the respondent needed to see a doctor but could not because of cost. The primary clinical outcome was vascular morbidity—a composite of stroke, retinopathy, nonhealing foot sores or bilateral foot amputations.

KEY RESULTS

Among the 11,274 diabetics with CHD, 1,541 (13.7 %) reported financial barriers to health care. Compared to individuals without financial barriers, those with financial barriers had significantly reduced rates of medical assessments within the past 2 years, hemoglobin (Hgb) A1C measurements in the past year, cholesterol measurements at any time, eye and foot examinations within the past year, diabetic education, antihypertensive treatment, aspirin use and a higher prevalence of vascular morbidity. In multivariable analyses, financial barriers to health care were independently associated with reduced odds of medical checkups (Odds Ratio [OR], 0.61; 95 % Confidence Intervals [CI], 0.55–0.67), Hgb A1C measurement (OR, 0.85; 95 % CI, 0.77–0.94), cholesterol measurement (OR, 0.76; 95 % CI, 0.67–0.86), eye (OR, 0.85; 95 % CI, 0.79–0.92) and foot (OR, 0.92; 95 % CI, 0.84–1.00) examinations, diabetic education (OR, 0.93; 95 % CI, 0.87–0.99), aspirin use (OR, 0.88; 95 % CI, 0.81–0.96) and increased odds of vascular morbidity (OR, 1.23; 95 % CI, 1.14–1.33).

CONCLUSIONS

In diabetic adults with CHD, financial barriers to health care were associated with impaired access to medical care, inferior quality of care and greater vascular morbidity. Eliminating financial barriers and adherence to guideline-based recommendations may improve the health of individuals with multiple chronic diseases.     

Breast-feeding and maternal risk of type 2 diabetes: a prospective study and meta-analysis

Aims/hypothesis

We aimed to examine the association between breast-feeding and maternal risk of type 2 diabetes and to investigate whether this association is mediated by anthropometric and biochemical factors.

Methods

A case–cohort study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study between 1994 and 2005 including 1,262 childbearing women (1,059 in a random sub-cohort and 203 incident cases) mainly aged between 35 and 64 years at baseline was applied. Self-reported lifetime duration of breast-feeding was assessed by questionnaire. Blood samples were used for biomarker measurement (HDL-cholesterol, triacylglycerols, C-reactive protein, fetuin-A, γ-glutamyltransferase, adiponectin). A systematic literature search and meta-analysis was conducted of prospective cohort studies investigating breast-feeding and risk of type 2 diabetes.

Results

The HR for each additional 6 months of breast-feeding was 0.73 (95% CI 0.56, 0.94) in EPIC-Potsdam. Meta-analysis of three previous prospective studies and the current study revealed an inverse association between breast-feeding duration and risk of diabetes (pooled HR for lifetime breast-feeding duration of 6–11 months compared with no breast-feeding 0.89; 95% CI 0.82, 0.97). Adjustment for BMI and waist circumference attenuated the association (HR per six additional months in EPIC-Potsdam 0.80; 95% CI 0.61, 1.04). Further controlling for potentially mediating biomarkers largely explained this association (HR 0.89; 95% CI 0.68, 1.16).

Conclusions/interpretation

Longer duration of breast-feeding may be related to a lower risk of diabetes. This potentially protective effect seems to be reflected by a more favourable metabolic profile; however, the role of body weight as a mediator or confounder remains uncertain.     

Needle Size Has Only a Limited Effect on Outcomes in EUS-Guided Fine Needle Aspiration: A Systematic Review and Meta-Analysis

Background

Several recent studies have investigated the utility of 19-, 22-, and 25-gauge needles in endoscopic ultrasound-guided fine needle aspiration (EUS–FNA) of pancreatic and peri-pancreatic tumors.

Aim

The objective of this study was to summarize data from these studies and estimate the effect of needle size on reported outcomes such as accuracy, adequacy, and complications.

Methods

Systematic review and meta-analysis comparing the effect of needle size (19, 22, and 25G) on diagnostic accuracy, adequacy, number of needle passes, and complications.

Results

25G appear to confer an advantage in adequacy rates relative to 22G needles (risk difference = 0.12 %, 95 % CI 0.01, 0.25). There was no significant difference in accuracy with an overall sensitivity and specificity for 22G being 0.78 (95 % CI 0.74–0.81) and 1.00 (95 % CI 0.98–1.00) and an overall sensitivity and specificity for 25G being 0.91 (95 % CI 0.87–0.94) and 1.00 (95 % CI 0.97–1.00). There was no difference in number of passes or complications between 25 and 22G. The limited data available regarding 19G needles do not show evidence of improved outcomes with these devices.

Conclusions

In the evaluation of pancreatic and peri-pancreatic lesions by EUS–FNA, 25G needles may confer an advantage in adequacy relative to 22G needles but confer no advantages with respect to accuracy, number of passes, or complications.     

Prognostic impact of LDH levels in patients with relapsed/refractory seminoma

Purpose

To evaluate the impact of age and LDH levels in patients with relapsed seminoma.

Methods

Data on the 204 seminoma from the International Prognostic Factor Study Group (IPFSG) were analyzed. All patients experienced unequivocal relapse/progression after at least three cisplatin-based chemotherapy cycles. Age and LDH at relapse were assessed in addition to previously identified prognostic factors for all germ cell tumor patients from the database (J Clin Oncol 28:4906, 2010).

Results

The impact of the IPFSG score remained highly significant in multivariate analysis. In addition, LDH ≥1.5 times the upper limit of normal (ULN) was significant in univariate (HR 1.96; CI 1.06–3.61) and multivariate analysis (HR 1.90; CI 1.00–3.62). Age, however, was not significant. Therefore, LDH was incorporated into a modified new IPFSG seminoma score by moving patients to the next unfavorable group for patients with LDH values ≥1.5 × ULN. Three prognostic groups were thus generated, which better subdivided seminoma patients than the original IPFSG score. Progression-free survival at 2 years: “very low risk” (n = 23) 85.7 % (95 % CI 62–95), “low risk” (n = 44) 62.7 % (95 % CI 46–75) and “intermediate risk” (n = 36) 35.1 % (95 % CI 20–51). Overall survival at 3 years: “very low risk” 88.8 % (95 % CI 62–97), “low risk” 71.3 % (95 % CI 55–83) and “intermediate risk” 51.3 % (95 % CI 33–67).

Conclusion

The addition of LDH, but not age, improves the impact of the IPFSG prognostic score in seminoma patients relapsing or progressing after cisplatin-based chemotherapy.     

Endoscopic Ultrasound Elastography for Differential Diagnosis of Pancreatic Masses: A Meta-Analysis

Background

Distinguishing malignant from benign pancreatic tumors is challenging with current imaging techniques. Endoscopic ultrasound (EUS) elastography has further improved the efficacy of EUS for characterizing pancreatic lesions.

Aims

To assess, by combining data from existing trials, the accuracy of EUS elastography in diagnosing malignant tumors for patients with pancreatic masses.

Methods

All relevant studies published were identified by systematic searching of databases. A meta-analysis was performed using a random-effects model to combine study results.

Results

Seven studies involving 752 patients were included. The sensitivity of EUS elastography for differential diagnosis of solid pancreatic masses was 97 % (95 % CI, 0.95–0.98), and the specificity was 76 % (95 % CI, 0.69–0.82). The area under the curve under summary receiver operating characteristic (SROC) was 0.9529. The combined positive likelihood ratio was 3.71 (95 % CI, 2.72–5.07), and the negative likelihood ratio was 0.05 (95 % CI, 0.02–0.13).

Conclusion

Our meta-analysis shows that EUS elastography is a useful tool for differential diagnosis of solid pancreatic neoplasms with very high sensitivity and relatively low specificity. The results indicate that EUS elastography not only provides information complementary to that from EUS but also potentially increases the yield of fine needle aspiration and reduces the number of unnecessary biopsies.     

ERCP with Probe-Based Confocal Laser Endomicroscopy for the Evaluation of Dominant Biliary Stenoses in Primary Sclerosing Cholangitis Patients

Background and Study Aim

The incidence of cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) ranges between 7 and 14 %. Despite using multiple tissue sampling modalities, detection of CCA remains a challenge. Probe-based confocal laser endomicroscopy (pCLE) has been utilized to visualize subepithelial biliary mucosa in patients with indeterminate strictures. We assessed the technical feasibility and operating characteristics of pCLE in a cohort of PSC patients with dominant biliary strictures (DS).

Patients and Methods

This was a chart review of a prospectively maintained database at a single tertiary referral center of 15 PSC patients with 21 dominant stenoses undergoing pCLE. A data collection sheet included demographics, ERCP, cholangioscopy, pCLE (Miami criteria), tissue sampling results, and follow-up to 12 months or liver transplantation. Operating characteristics for pCLE and ERCP tissue sampling were calculated.

Results

Sufficient visualization of DS by pCLE was achieved in 20/21 (95 %). pCLE sensitivity, specificity, PPV, and NPV were 100 % (95 % CI 19.3–100 %), 61.1 % (95 % CI 35.8–82.6 %), 22.2 % (95 % CI 3.5–59.9 %), and 100 % (95 % CI 71.3–100 %), respectively, in detecting neoplasia. In comparison, concomitant tissue sampling yielded sensitivity, specificity, PPV, and NPV of 0 % (95 % CI 0–80.7 %), 94.4 % (95 % CI 72.6–99.1 %), 0 % (95 % CI 0–83.5 %), and 89.5 % (95 % CI 66.8–98.4 %), respectively.

Conclusions

pCLE achieves a high technical success rate in patients with PSC and DS. This single center, small series, suggests that pCLE may have a high sensitivity and negative predictive value to exclude neoplasia. If verified in larger prospective studies, the technology may be utilized to risk stratify dominant strictures in patients with PSC.     

Responsiveness of neoadjuvant chemotherapy before surgery predicts favorable prognosis for cervical cancer patients: a meta-analysis

Background

Neoadjuvant chemotherapy (NAC) before surgery has already shown the therapy effectiveness in patients with cervical cancer. The present meta-analysis was conducted to determine whether the response to NAC predicts for prognosis.

Methods

Systematic computerized searches of the PubMed and Web of Knowledge were performed. Prognosis outcomes included progression-free survival (PFS), and overall survival (OS). The pooled odd ratio (OR) was estimated by using fixed-effect model or random-effect model according to heterogeneity between studies.

Results

Eighteen studies with 1,785 patients were included. Cisplatin-based NAC treatments were most commonly used. The clinical response rate ranged from 48.4 to 93.0 %, and the pathological response rate ranged from 27.6 to 30.6 %. The pooled ORs estimating the association of PFS with NAC response were 5.707 (95 % CI 3.564–9.137), 6.798 (95 % CI 4.716–9.799), 6.327 (95 % CI 4.398–9.102), and 5.214 (95 % CI 3.748–7.253) at 1-, 2-, 3-, and 5-year follow-up, respectively, and the pooled ORs estimating the association of OS with NAC response were 6.179 (95 % CI 3.390–11.264), 9.155 (95 % CI 5.759–14.555), 8.431 (95 % CI 5.667–12.543), and 5.785 (95 % CI 4.124–8.115) at 1-, 2-, 3-, and 5-year follow-up, respectively. No obvious statistical heterogeneity was detected. Funnel plots and Egger’s tests did not reveal publication bias. Sensitivity analysis showed the results of meta-analysis were robust.

Conclusion

This meta-analysis confirms that response to NAC is an indicator for PFS and OS, and suggests that patients-achieving response of NAC before surgery predicts favorable prognosis for cervical cancer patients.     

Get Screened: A Randomized Trial of the Incremental Benefits of Reminders, Recall, and Outreach on Cancer Screening

BACKGROUND

Rates of breast cancer (BC) and colorectal cancer (CRC) screening are particularly low among poor and minority patients. Multifaceted interventions have been shown to improve cancer-screening rates, yet the relative impact of the specific components of these interventions has not been assessed. Identifying the specific components necessary to improve cancer-screening rates is critical to tailor interventions in resource limited environments.

OBJECTIVE

To assess the relative impact of various components of the reminder, recall, and outreach (RRO) model on BC and CRC screening rates within a safety net practice.

DESIGN

Pragmatic randomized trial.

PARTICIPANTS

Men and women aged 50–74 years past due for CRC screen and women aged 40–74 years past due for BC screening.

INTERVENTIONS

We randomized 1,008 patients to one of four groups: (1) reminder letter; (2) letter and automated telephone message (Letter + Autodial); (3) letter, automated telephone message, and point of service prompt (Letter + Autodial + Prompt); or (4) letter and personal telephone call (Letter + Personal Call).

MAIN MEASURES

Documentation of mammography or colorectal cancer screening at 52 weeks following randomization.

KEY RESULTS

Compared to a reminder letter alone, Letter + Personal Call was more effective at improving screening rates for BC (17.8 % vs. 27.5 %; AOR 2.2, 95 % CI 1.2–4.0) and CRC screening (12.2 % vs. 21.5 %; AOR 2.0, 95 % CI 1.1–3.9). Compared to letter alone, a Letter + Autodial + Prompt was also more effective at improving rates of BC screening (17.8 % vs. 28.2 %; AOR 2.1, 95 % CI 1.1–3.7) and CRC screening (12.2 % vs. 19.6 %; AOR 1.9, 95 % CI 1.0–3.7). Letter + Autodial was not more effective than a letter alone at improving screening rates.

CONCLUSIONS

The addition of a personal telephone call or a patient-specific provider prompt were both more effective at improving mammogram and CRC screening rates compared to a reminder letter alone. The use of automated telephone calls, however, did not provide any incremental benefit to a reminder letter alone.     

No increased mortality in patients with rheumatoid arthritis treated with biologics: results from the biologics register of six rheumatology institutes in Japan

Objective

To investigate the influence of biologics on mortality and risk factors for death in rheumatoid arthritis (RA) patients.

Methods

RA patients treated with at least one dose of biologics in daily practice in six large rheumatology institutes (“biologics cohort”) were observed until 15 May 2010 or death, whichever occurred first. Mortality of the biologics cohort and the “comparator cohort” (comprising patients among the IORRA cohort who had never been treated with biologics) was compared to that of the Japanese general population. Factors associated with mortality were assessed by a Cox model.

Results

Among 2683 patients with 6913.0 patient-years of observation, 38 deaths were identified in the biologics cohort. The probability of death in patients lost to follow-up, calculated using the weighted standardized mortality ratio (SMR), was 1.08 [95 % confidence interval (CI) 0.77–1.47] in the biologics cohort and 1.28 (95 % CI 1.17–1.41) in the comparator cohort. Pulmonary involvement was the main cause of death (47.4 %), and the disease-specific SMR of pneumonia was 4.19 (95 % CI 1.81–8.25). Risk factors for death included male gender [hazard ratio (HR) 2.78 (95 % CI 1.24–6.22)], advanced age (HR 1.07, 95 % CI 1.03–1.11), and corticosteroid dose (HR 1.08, 95 % CI 1.01–1.17).

Conclusion

Mortality in RA patients exposed to biologics did not exceed that in patients not exposed to biologics, but death from pulmonary manifestations was proportionally increased in RA patients exposed to biologics.     

Specialty,Political Affiliation,and Perceived Social Responsibility Are Associated with U.S. Physician Reactions to Health Care Reform Legislation

BACKGROUND

Little is known about how U.S. physicians’ political affiliations, specialties, or sense of social responsibility relate to their reactions to health care reform legislation.

OBJECTIVE

To assess U.S. physicians’ impressions about the direction of U.S. health care under the Affordable Care Act (ACA), whether that legislation will make reimbursement more or less fair, and examine how those judgments relate to political affiliation and perceived social responsibility.

DESIGN

A cross-sectional, mailed, self-reported survey.

PARTICIPANTS

Simple random sample of 3,897 U.S. physicians.

MAIN MEASURES

Views on the ACA in general, reimbursement under the ACA in particular, and perceived social responsibility.

KEY RESULTS

Among 2,556 physicians who responded (RR2: 65 %), approximately two out of five (41 %) believed that the ACA will turn U.S. health care in the right direction and make physician reimbursement less fair (44 %). Seventy-two percent of physicians endorsed a general professional obligation to address societal health policy issues, 65 % agreed that every physician is professionally obligated to care for the uninsured or underinsured, and half (55 %) were willing to accept limits on coverage for expensive drugs and procedures for the sake of expanding access to basic health care. In multivariable analyses, liberals and independents were both substantially more likely to endorse the ACA (OR 33.0 [95 % CI, 23.6–46.2]; OR 5.0 [95 % CI, 3.7–6.8], respectively), as were physicians reporting a salary (OR 1.7 [95 % CI, 1.2–2.5]) or salary plus bonus (OR 1.4 [95 % CI, 1.1–1.9) compensation type. In the same multivariate models, those who agreed that addressing societal health policy issues are within the scope of their professional obligations (OR 1.5 [95 % CI, 1.0–2.0]), who believe physicians are professionally obligated to care for the uninsured / under-insured (OR 1.7 [95 % CI, 1.3–2.4]), and who agreed with limiting coverage for expensive drugs and procedures to expand insurance coverage (OR 2.3 [95 % CI, 1.8–3.0]), were all significantly more likely to endorse the ACA. Surgeons and procedural specialists were less likely to endorse it (OR 0.5 [95 % CI, 0.4–0.7], OR 0.6 [95 % CI, 0.5–0.9], respectively).

CONCLUSIONS

Significant subsets of U.S. physicians express concerns about the direction of U.S. health care under recent health care reform legislation. Those opinions appear intertwined with political affiliation, type of medical specialty, as well as perceived social responsibility.