Zhao-Shen Li

Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review

BACKGROUND Capsule endoscopy (CE) has been widely used in clinical practice. OBJECTIVE To provide systematically pooled results on the indications and detection, completion, and retention rates of small-bowel CE. DESIGN A systematic review. MAIN OUTCOME MEASUREMENTS We searched the PubMed database (2000-2008) for original articles relevant to small-bowel CE for the evaluation of patients with small-bowel signs and symptoms. Data on the total number of capsule procedures, the distribution of different indications for the procedures, the percentages of procedures with positive detection (detection rate), complete examination (completion rate), or capsule retention (retention rate) were extracted and/or calculated, respectively. In addition, the detection, completion, and retention rates were also extracted and/or calculated in relation to indications such as obscure GI bleeding (OGIB), definite or suspected Crohns disease (CD), and neoplastic lesions. RESULTS A total of 227 English-language original articles involving 22,840 procedures were included. OGIB was the most common indication (66.0%), followed by the indication of only clinical symptoms reported (10.6%), and definite or suspected CD (10.4%). The pooled detection rates were 59.4%; 60.5%, 55.3%, and 55.9%, respectively, for overall, OGIB, CD, and neoplastic lesions. Angiodysplasia was the most common reason (50.0%) for OGIB. The pooled completion rate was 83.5%, with the rates being 83.6%, 85.4%, and 84.2%, respectively, for the 3 indications. The pooled retention rates were 1.4%, 1.2%, 2.6%, and 2.1%, respectively, for overall and the 3 indications. LIMITATIONS Inclusion and exclusion criteria were loosely defined. CONCLUSIONS The pooled detection, completion, and retention rates are acceptable for total procedures. OGIB is the most common indication for small-bowel CE, with a high detection rate and low retention rate. In addition, angiodysplasia is the most common finding in patients with OGIB. A relatively high retention rate is associated with definite or suspected CD and neoplasms.

Risk factors for ERCP-related complications: a prospective multicenter study.

OBJECTIVES:To investigate the potential risk factors for endoscopic retrograde cholangiopancreatography (ERCP) complications and to identify whether the risk factors are different for pancreatitis and asymptomatic hyperamylasemia.METHODS:Consecutive ERCP procedures were studied at 14 centers in China from May 2006 to April 2007. The complications after the patients’ first-only procedures were evaluated. Multivariate analysis based on the first-only procedures was used to identify the risk factors.RESULTS:A total of 3,178 procedures were performed on 2,691 patients. Overall, complications developed in 213 (7.92%) patients, pancreatitis in 116 (4.31%), and asymptomatic hyperamylasemia in 396 (14.72%). In the multivariate analysis, female gender (adjusted odds ratios (ORs): 1.52, 95% confidence interval (CI): 1.14–2.02, P=0.004), periampullary diverticulum (OR: 2.02, 95% CI: 1.49–2.73, P<0.001), cannulation time >10 min (OR: 1.51, 95% CI: 1.08–2.10, P=0.016), ≥1 pancreatic deep wire pass (OR: 1.80, 95% CI: 1.33–2.42, P<0.001), and needle-knife precut (OR: 2.70, 95% CI: 1.42–5.14, P=0.002) were risk factors for overall complications. Female gender (OR: 1.84, 95% CI: 1.25–2.70, P=0.002), age ≤60 year (OR: 1.59, 95% CI: 1.06–2.39, P=0.025), cannulation time>10 min (OR: 1.76, 95% CI: 1.13–2.74, P=0.012), ≥1 pancreatic deep wire pass (OR: 2.77, 95% CI: 1.79–4.30, P<0.001), and needle-knife precut (OR: 4.34, 95% CI: 1.92–9.79, P<0.001) were risk factors for pancreatitis. Cannulation time>10 min (OR: 1.96, 95% CI: 1.52–2.54, P<0.001), ≥1 pancreatic deep wire pass (OR: 2.24, 95% CI: 1.74–2.89, P<0.001), needle-knife precut (OR: 2.34, 95% CI: 1.32–4.14, P=0.004), and major papilla pancreatic sphincterotomy (OR: 1.71, 95% CI: 1.23–2.37, P=0.001) were risk factors for asymptomatic hyperamylasemia.CONCLUSIONS:Patient-related factors are as important as procedure-related factors in determining high-risk predictors for post-ERCP overall complications and pancreatitis. However, the risk factors for asymptomatic hyperamylasemia may be mostly procedure related.

Serum MicroRNA Expression Profile as a Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer

BACKGROUND Detection of pancreatic cancer (PaC), particularly at early stages, remains a great challenge owing to lack of specific biomarkers. We sought to identify a PaC-specific serum microRNA (miRNA) expression profile and test its specificity and sensitivity as a biomarker in the diagnosis and prognosis of PaC. METHODS We obtained serum samples from 197 PaC cases and 158 age- and sex-matched cancer-free controls. We screened the differentially expressed serum miRNAs with Illumina sequencing by synthesis technology using pooled serum samples followed by RT-qPCR validation of a large number of samples arranged in multiple stages. We used risk score analysis to evaluate the diagnostic value of the serum miRNA profiling system. To assess the serum miRNA-based biomarker accuracy in predicting PaC, we performed additional double-blind testing in 77 PaC cases and 52 controls and diagnostic classification in 55 cases with clinically suspected PaC. RESULTS After the selection and validation process, 7 miRNAs displayed significantly different expression levels in PaC compared with controls. This 7 miRNA-based biomarker had high sensitivity and specificity for distinguishing various stages of PaC from cancer-free controls and also accurately discriminated PaC patients from chronic pancreatitis (CP) patients. Among the 7 miRNAs, miR-21 levels in serum were significantly associated with overall PaC survival. The diagnostic accuracy rate of the 7-miRNA profile was 83.6% in correctly classifying 55 cases with clinically suspected PaC. CONCLUSIONS These data demonstrate that the 7 miRNA-based biomarker can serve as a novel noninvasive approach for PaC diagnosis and prognosis.

Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer

This study was performed to identify plasma microRNAs (miRNAs) as diagnostic biomarkers for pancreatic cancer (PCa) and to assess their supplementary role with serum CA19‐9 in early identification of tumors. Plasma RNAs were extracted from 140 PCa patients, 111 chronic pancreatitis (CP) patients and 68 normal controls, and the relative abundances of seven miRNAs (miR‐16, 21, 155, 181a, 181b, 196a and 210) were measured using real‐time PCR. Their diagnostic utility for PCa and correlation with clinical characteristics were analyzed. All seven miRNAs were significantly aberrantly upregulated in the PCa group compared with both the CP and normal groups, between which only four miRNAs (miR‐155, 181a, 181b and 196a) were significantly different. Logistic modeling proved that only miR‐16 and miR‐196a possessed an independent role in discriminating PCa from normal and CP. Furthermore, after including serum CA19‐9 in the logistic model, the combination of miR‐16, miR‐196a and CA19‐9 was more effective for discriminating PCa from non‐PCa (normal+CP) (AUC‐ROC, 0.979; sensitivity, 92.0%; specificity, 95.6%), and for discriminating PCa from CP (AUC‐ROC, 0.956; sensitivity, 88.4%; specificity, 96.3%) compared with the miRNA panel (miR‐16+miR‐196a) or CA19‐9 alone. Most significantly, the combination was effective at identification of tumors in Stage 1 (85.2%). In conclusion, plasma miRNAs were effective for distinguishing PCa from non‐PCa (normal+CP). The combination of miR‐16, miR‐196a and CA19‐9 was more effective for PCa diagnosis, especially in early tumor screening.

Prophylactic Antibiotics Cannot Reduce Infected Pancreatic Necrosis and Mortality in Acute Necrotizing Pancreatitis: Evidence From a Meta-Analysis of Randomized Controlled Trials

BACKGROUND:There is no agreement whether intravenous prophylactic antibiotics can reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis (ANP). We performed a meta-analysis comparing intravenous antibiotics with placebo or no treatment in randomized controlled trials (RCTs).METHODS:Databases including MEDLINE, EMBASE, the Cochrane controlled trials register, the Cochrane Library, and Science Citation Index were searched to find relevant trials. Outcome measures were infected necrosis and mortality.RESULTS:Seven trials involving 467 patients were included. Analysis suggested infected pancreatic necrosis rates were not significantly different (antibiotics 17.8%, controls 22.9%), RR 0.81 (95% CI 0.54–1.22). There was nonsignificantly decreased mortality with antibiotics (9.3%) versus controls (15.2%), RR 0.70 (95% CI 0.42–1.17). Subsequent subgroup analysis confirmed antibiotics were not statistically superior to controls in reduction of infected necrosis and mortality.CONCLUSIONS:Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in patients with ANP.

Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review

BACKGROUND EUS-guided FNA (EUS-FNA) permits both morphologic and cytologic analysis of lesions within or adjacent to the GI tract. Although previous studies have evaluated the accuracy of EUS-FNA, little is known about the complications of EUS-FNA. Moreover, the frequency and severity of complications may vary from center to center and may be related to differences in individual experience. OBJECTIVE To systematically review the morbidity and mortality associated with EUS-FNA. DESIGN MEDLINE and EMBASE were searched to identify relevant English-language articles. MAIN OUTCOME MEASUREMENTS EUS-FNA-specific morbidity and mortality rates. RESULTS We identified 51 articles with a total of 10,941 patients who met our inclusion and exclusion criteria; the overall rate of EUS-FNA-specific morbidity was 0.98% (107/10,941). In the small proportion of patients with complications of any kind, the rates of pancreatitis (36/8246; 0.44%) and postprocedure pain (37/10,941; 0.34%) were 33.64% (36/107) and 34.58% (37/107), respectively. The mortality rate attributable to EUS-FNA-specific morbidity was 0.02% (2/10,941). Subgroup analysis showed that the morbidity rate was 2.44% in prospective studies compared with 0.35% in retrospective studies for pancreatic mass lesions (P=.000), whereas it was 2.33% versus 5.07% for pancreatic cysts (P=.036). LIMITATIONS Few articles reported well-designed, prospective studies and few focused on overall complications after EUS-FNA. CONCLUSIONS EUS-FNA-related morbidity and mortality rates are relatively low, and most associated events are mild to moderate in severity.

Body Mass Index Increases Risk for Colorectal Adenomas Based on Meta-analysis

BACKGROUND & AIMS There have been inconsistent results published about the relationship between excess body weight, expressed as increased body mass index (BMI), and risk of colorectal adenoma (CRA). We conducted a meta-analysis to explore this relationship. We focused on whether the relationship varied based on the sex of the study subjects, study design, features of the polyps, or potential confounders, including alcohol use, nonsteroidal anti-inflammatory drug use, smoking, and exercise. METHODS We identified studies by performing a literature search of Medline, EMBASE, and ISI Web of Science through July 31, 2011, and by searching the reference lists of pertinent articles. We analyzed 36 independent studies, which included 29,860 incident cases of CRA. Summary relative risks with their 95% confidence intervals (CIs) were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochrans Q statistic and I(2) analyses. RESULTS Overall, a 5-unit increase in BMI (calculated as kg/m(2)) increased the risk for CRA (summary relative risk = 1.19; 95% CI: 1.13-1.26), although there was a high level of heterogeneity among studies (P(heterogeneity) < .001; I(2) = 76.8%). Subgroup analyses revealed that the increased risk of CRA in obese individuals was independent of race, geographic location, study design, sex, adenoma progression, and confounders. The association between increased BMI and risk for CRA was stronger for colon than rectal adenoma. CONCLUSIONS Based on a meta-analysis, increased BMI increases the risk for colon but not rectal adenoma. Unlike colorectal cancer, there is no sex difference in the relationship between increased BMI and risk of CRA.

Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study.

BACKGROUND AND STUDY AIMS Intraoperative and transdermal ultrasonography-mediated brachytherapy has been proved to be effective in postponing the development of abdominal carcinomas. The main purpose of this study was to evaluate the clinical efficacy and safety of endoscopic ultrasonography (EUS)-guided interstitial implantation of radioactive iodine 125 seeds in advanced pancreatic cancer. PATIENTS AND METHODS In total, 22 patients with advanced pancreatic cancer and positive fine-needle aspiration results underwent EUS-guided interstitial implantation of iodine seeds. All enrolled patients received routine gemcitabine-based 5-fluorouracil chemotherapy 1 week after brachytherapy. RESULTS All 22 patients were successfully implanted with 125I seeds via EUS, with a median of 10 seeds and a maximum of 30 seeds per procedure. The median follow-up time of patients was 9.3 months, and the estimated median survival time was 9.0 months (95 % confidence interval 6.7 - 11.3 months). Partial remission was achieved in three cases (13.6 %) during the 4-week period, and disease in 10 patients (45.5 %) remained stable. Cancer finally progressed in 20 patients, all of whom died during 2 years of follow-up. Visual analog scale pain score dropped from 5.07 +/- 2.63 to 1.73 +/- 1.91 ( P< 0.01) 1 week after brachytherapy but increased again to 3.53 +/- 1.51 1 month later ( P< 0.05 vs. baseline). There were no obvious complications following therapy. CONCLUSIONS EUS-guided interstitial implantation of 125I seeds may represent a safe alternative treatment option for locally advanced pancreatic cancer. Our preliminary data suggest improvement in pain, but no long-term survival benefit.

Genome-wide association study identifies five loci associated with susceptibility to pancreatic cancer in Chinese populations.

Pancreatic cancer has the lowest survival rate among human cancers, and there are no effective markers for its screening and early diagnosis. To identify genetic susceptibility markers for this cancer, we carried out a genome-wide association study on 981 individuals with pancreatic cancer (cases) and 1,991 cancer-free controls of Chinese descent using 666,141 autosomal SNPs. Promising associations were replicated in an additional 2,603 pancreatic cancer cases and 2,877 controls recruited from 25 hospitals in 16 provinces or cities in China. We identified five new susceptibility loci at chromosomes 21q21.3, 5p13.1, 21q22.3, 22q13.32 and 10q26.11 (P = 2.24 × 10−13 to P = 4.18 × 10−10) in addition to 13q22.1 previously reported in populations of European ancestry. These results advance our understanding of the development of pancreatic cancer and highlight potential targets for the prevention or treatment of this cancer.

Oncogenic K-Ras requires activation for enhanced activity

Oncogenic Ras mutations are widely considered to be locked in a permanent ‘On’ state and ‘constitutively active’. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.