Subsequent Surveillance Research Articles

Role of endoscopy in the staging and management of colorectal cancer

Role of endoscopy in the staging and management of colorectal cancer

Massive Left Atrial Thrombus in a Patient With Rheumatic Mitral Stenosis and Atrial Fibrillation While Anticoagulated With Dabigatran

Dabigatran is an oral direct thrombin inhibitor licensed for use by the Food and Drug Administration.1,2 This novel anticoagulant is effective and approved for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation (AF) and prevention of venous thromboembolism in adults receiving elective total hip or knee replacement surgery.1,2 These images present a cautionary account of failed dabigatran anticoagulation in a patient with valvular AF: an indication for which its use has not been approved. A 50-year-old female with severe rheumatic mitral stenosis underwent open mitral valvotomy under cardiopulmonary bypass 25 years prior. On subsequent annual surveillance, she remained asymptomatic and her mitral stenosis remained moderate on echocardiography with a mean transmitral gradient of 8 mm Hg. Permanent AF was previously diagnosed 12 months earlier, and she was commenced on warfarin and metoprolol. She had stable anticoagulation monitoring, no bleeding complications, and normal renal function, but was needle-phobic with psychological …

A Single-Center Experience with Luminal Venous Cannulae Obstruction Caused by Clot Formation during Bypass

Our institution experienced two bypass cases from January through December 2011 in which venous return was significantly variable and at times poor. Luminal clot formation in the venous cannulae was found in each case postbypass. These events were captured and monitored through our institution’s Non-Routine Event Reporting Program and eventually reported to the Food and Drug Administration (FDA). We began inspecting all venous cannulae postbypass in December 2011. During a subsequent 9-month surveillance period, we documented 33 venous cannulae in 21 patients with luminal clot formation. Only one cannula during this surveillance period required change-out on bypass. The manufacturer eventually identified changes in production that likely caused the clotting events. The manufacturer modified their production methods and began supplying cannulae produced under the new method in September 2012. We have experienced only one clotting event with the new cannulae and in that instance, the metal tip was found to be defective. We recommend inspection of all venous cannulae postbypass with internal, manufacturer, and FDA reporting for those noted to have luminal clot formation.

Triple metachronous colon cancer

A 72-year-old male with an early stage "node-negative" sigmoid colon cancer developed 2 separate "node-negative" early stage colon cancers during a subsequent colonoscopy surveillance regimen, the first in the descending colon 7 years later, and the second in the cecum almost 14 years after the first cancer was resected. After the initial symptomatic cancer, all subsequent neoplastic disease, including malignant cancers were completely asymptomatic. This entity, multiple primary cancers, likely reflected the use of a colonoscopic surveillance regimen.

Nationwide survey of the development of drug-resistant pathogens in the pediatric field in 2007 and 2010: drug sensitivity of Streptococcus pneumoniae in Japan (second report).

We previously conducted nationwide surveillance of Streptococcus pneumoniae in 2000–2001 (period 1) and 2004 (period 2) and reported the findings. Subsequent surveillance surveys conducted in 2007 (period 3) and 2010 (period 4) are now reported. Bacterial strains were clinically isolated from children with meningitis, sepsis, and respiratory tract infections at 27 hospitals participating in the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Twenty-one drugs were investigated for 283 isolated strains in period 3, and 24 drugs were investigated for 459 strains in period 4. In period 3, 43.8 % of strains were penicillin-susceptible S. pneumoniae (PSSP), 52.3 % were penicillin-intermediate S. pneumoniae (PISP), and 3.9 % were penicillin-resistant S. pneumoniae (PRSP). In period 4, the percentages were PSSP 23.1 %, PISP 49.9 %, and PRSP 27.0 %. The resistance rates were 56.2 % and 76.9 %, respectively. Drug sensitivity was best with panipenem, at a minimum inhibitory concentration (MIC)90 ≤0.063 μg/ml in period 3, and with tebipenem (MIC90 ≤ 0.063 μg/ml) in period 4. Patients’ background factors related to increased bacterial resistance were investigated, and significant differences were found depending on whether a child had siblings (P = 0.0056) or was a daycare center attendee (P = 0.0195) in period 3, and age category (P = 0.0256) in period 4. No factors were common to both periods 3 and 4. Pneumococcus is a major causative organism of pediatric infectious disease, and we plan to continue conducting surveillance and providing information in the future.

Intestinal Metaplasia Recurs Infrequently in Patients Successfully Treated for Barrett's Esophagus With Radiofrequency Ablation

Radiofrequency ablation (RFA) of Barrett's esophagus (BE) is safe and effective in eradicating dysplasia and intestinal metaplasia, and may reduce rates of esophageal adenocarcinoma (EAC). We assessed rates of and risk factors for disease recurrence after successful treatment of BE with RFA. We performed a retrospective cohort study of patients who completed RFA for dysplastic BE or intramucosal carcinoma (IMC), achieved complete eradication of dysplasia (CE-D) or intestinal metaplasia (CE-IM), and underwent subsequent endoscopic surveillance at a single center. Rates of disease recurrence and progression were determined. Patients with and without recurrent disease were compared to determine risk factors for recurrence. Two hundred and sixty-two subjects underwent RFA during the study period. Of these, 119 and 112 patients were retained in endoscopic surveillance after CE-D and CE-IM, respectively. Median observation time was 397 days (range: 54-1,668 days). Eight patients (7% of those with CE-IM) had recurrent disease after a median of 235 days (range 55-1,124 days). Progression to IMC (n=1) or EAC (n=2) occurred in three of these eight patients, all of whom had pre-ablation high-grade dysplasia (HGD). Five patients had recurrence of non-dysplastic BE (n=3), low-grade dysplasia (n=1), and HGD (n=1). During 155 patient-years of observation, recurrence occurred in 5.2%/year, and progression occurred in 1.9%/year. No clinical characteristics were associated with disease recurrence. In patients with BE and dysplasia or early cancer who achieved CE-IM, BE recurred in ≈ 5%/year. Patient characteristics did not predict recurrence. Subjects undergoing RFA for dysplastic BE should be retained in endoscopic surveillance.

High Definition Technology can Enhance Adenoma Detection in Inflammatory Bowel Disease Patients

Patients with inflammatory bowel disease (IBD) have increased risk for the development of colorectal carcinoma. In previous studies, 3.6% of patients were reported to have adenomas detected on surveillance colonoscopies. It has also been reported that high definition (HD) colonoscopes have improved targeted detection of dysplastic lesions in IBD. This study evaluated the detection of colitis-associated dysplasia and adenomas using HD colonoscopes. Medical records of consecutive patients seen in an IBD program at a university gastroenterology practice were evaluated. Patient age, gender, race, disease type (UC, CD), date of diagnostic colonoscopy and subsequent surveillance colonoscopies were obtained. Colitis-associated dysplasia and adenomas detected prior to and following the initiation of HD technology were documented. Patients were excluded if they were lost to follow-up, underwent total colectomy with ileostomy and those transferring care to the practice without previous medical records. A database, maintaining patient confidentiality, was created using Microsoft Excel. Statistical analysis was performed using Fisher Exact test and t-test with significance set at P < 0.05. Medical records of 303 patients (179 females, 124 males) with IBD (130 UC, 173 CD) were evaluated. There were 170 white, 80 African-American and 53 of other or undocumented ethnicity. The mean age was 40 years. 31 patients (10%) had adenomas (23 UC, 8 CD). There was a significant difference (P = 0.004) in the rate of which adenomas were detected in patients with UC compared to CD. Additionally, there was a significant difference (P = 0.0001) in the rate at which adenomas were detected prior to HD technology (5.2%) and following HD technology (15.2%). There was no significant difference in the prevalence of adenomas based upon gender (P = 0.18), race (P = 0.84), or age (P = 0.29). Five (1.6%) patients had colitis-associated dysplasia (2UC, 3CD). 0 patients had dysplasia detected prior to HD technology and 5 patients were identified to have dysplasia detected following the introduction of HD technology (P = 0.06). There was no significant difference in prevalence of colitis-associated dysplasia based upon gender (P = 0.164), race (P = 0.39), age (P = 0.78) or disease type (P = 1.000) High definition colonoscopes have been reported to increase detection of dysplastic lesions in patients with IBD. While the sample size was too small to analyze the impact of HD on colitis-associated dysplasia, the detection of dysplasia following introduction of HD colonoscopes approached significance. However, this investigation revealed that there was a significant increase in the detection of adenomas in IBD patients using HD technology. While other potential factors, (i.e. pre-procedure cleansing, disease severity and skill of the endoscopist) can influence adenoma detection, recognition of the potential impact of HD technology is important. Physicians should utilize HD technology as much as possible when evaluating IBD patients to ensure optimum care.

Receipt of cancer treatment summaries and follow-up instructions among adult cancer survivors: results from a national survey

The purpose of this study is to examine reporting of treatment summaries and follow-up instructions among cancer survivors. Using the 2010 National Health Interview Survey, we created logistic regression models among cancer survivors not in treatment (n = 1,345) to determine characteristics associated with reporting treatment summaries and written follow-up instructions, adjusting for sociodemographic, access, and cancer-related factors. Findings are presented for all survivors and those recently diagnosed (≤4 years). We also examined unadjusted associations between written instructions and subsequent surveillance and screening. Among those recently diagnosed, 38 % reported receiving treatment summaries and 58 % reported written instructions. Among all survivors, approximately one third reported summaries and 44 % reported written instructions. After adjustment, lower reporting of summaries was associated with cancer site, race, and number of treatment modalities among those recently diagnosed, and white vs. black or Hispanic race/ethnicity, breast vs. colorectal cancer, >10 vs. ≤5 years since diagnosis, no clinical trials participation, and better than fair health among all survivors. For instructions, lower reporting was associated with no trials participation and lower income among those recently diagnosed, and increasing age, white vs. black race, lower income, >10 vs. ≤5 years since diagnosis, 1 vs. ≥2 treatment modalities, no trials participation, and at least good vs. fair/poor health among all survivors. Written instructions were associated with reporting provider recommendations for breast and cervical cancer surveillance, and recent screening mammograms. Many recently diagnosed cancer survivors did not report receiving treatment summaries and written follow-up instructions. Opportunities exist to examine associations between use of these documents and recommended care and outcomes, and to facilitate their adoption. Cancer survivors who have completed therapy should ask their providers for treatment summaries and written follow-up instructions, and discuss with them how their cancer and therapy impact their future health care.

Association and prognostic value of serum inflammation markers in patients with leukoplakia and oral cavity cancer

Oral cavity cancer ranks as the fourth leading cancer in men in Taiwan. The development of a serum biomarker panel for early detection and disease monitoring is, therefore, warranted. Nine inflammation-associated markers were investigated in 46 patients with leukoplakia, 151 patients with untreated oral cavity squamous cell carcinoma (OSCC), and 111 age- and gender-matched healthy controls using enzyme-linked immunosorbent assay. During a subsequent 28-month surveillance of OSCC patients, serum samples were prospectively collected at predetermined intervals following the completion of therapy. Logistic regression analysis showed matrix metalloproteases (MMP)-2, MMP-9, C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and E-selectin having the best discrimination power between groups and significant elevation trends of those five markers were noted from control to OSCC. By combining those five markers, a 0.888 and 0.938 area under curve by ROC curve analysis with 67.4% and 80% overall sensitivity and fixed 90% specificity for leukoplakia and OSCC groups were demonstrated. In the follow-up period, 25 OSCC patients developed recurring or secondary tumors. All examined markers had decreased in relapse-free patients following treatment. However, in patients with relapse, interleukin-6, CRP, and serum amyloid A remained at elevated levels. Statistical analysis showed that patients with CRP ≧2 mg/L and E-selectin ≧85 ng/mL at baseline had highest probability of relapse (odds ratio=3.029, p<0.05). The results indicate that inflammation plays a crucial role in the pathogenesis process of OSCC. By examining the inflammation markers, physicians could potentially identify patients at risk of cancer transformation or relapse.

Segmentation of Pedestrians with Confidence Level Computation

In this work, we propose a mechanism to segment groups of pedestrians with confidence level computation for intelligent surveillance systems. The goal is to specify the number of people and locate the position and size of each individual in groups of people. Human detection and clustering techniques are combined to achieve the segmentation purpose. The histogram of oriented gradients and curvelet features are extracted for full body detection using a support vector machine classifier. Modified Haar of Oriented Gradient features are constructed for upper body and lower body detectors. A clustering algorithm is then applied to the detected humans to eliminate the redundant detection responses. The proposed mechanism requires no prior assumptions of human sizes, human heights, camera distances, and other calibration parameters. Moreover, confidence level computation can provide valuable information for subsequent surveillance applications. The proposed approach is tested with pedestrian benchmark dataset and surveillance videos. The experimental results have demonstrated the effectiveness of the proposed pedestrian segmentation mechanism.

Management of Incidentally Detected Barrettʼs in a Young Person: a Markov Process Cost-Utility Analysis

Purpose: Esophagogastroduodenoscopies (EGDs) performed on young adults occasionally yield an incidental finding of Barrett's esophagus (BE). Population-based data suggest a BE prevalence of 0.5% in subjects between 20-50 years old and a malignant transformation of 0.02%-0.05% per year within that group. Because the benefit of endoscopic surveillance in this population is unknown, incidental BE in a young person presents the endoscopist with a management dilemma. Our study uses cost-utility analysis to compare four plausible strategies. Methods: We constructed a Markov model from a third-party payer perspective. A hypothetical cohort of 100,000 30-year-olds with incidentally detected BE was moved through the permitted states on yearly cycles until age of 80 years or death was reached. Transition probabilities were derived from 3 national population databases and studies from a large U.S. healthcare system. Costs, utilities, and discount rates were derived from published data. We compared four strategies: natural history (S1); endoscopic surveillance (S2); radiofrequency ablation (RFA) with no surveillance (S3); and RFA with endoscopic surveillance and salvage RFA for persistent BE (S4). The main outcome measure was the incremental cost-effectiveness ratio (ICER), calculated as difference in costs (US$) divided by difference in discounted quality-adjusted life-years (dQALY) between two strategies. Results: Compared with natural history, only strategy S3 was found be cost-effective under all plausible input assumptions. Selected ICERs were as follows: S2 versus S1 = $244,798/dQALY; S3 versus S1 = $49,511/dQALY; S4 versus S1 = $161,272/dQALY; S3 dominated S2; S4 versus S3 = $723,009/dQALY. The ICER of S3 remained robust over a broad range of variations tested in the 1-, 2-, and 3-way sensitivity analyses. Only under extreme simultaneous variations of multiple input parameters did S3 become cost-ineffective compared with S2 or S4. The strategy S2 became cost-effective compared with S3 only if EGD costs fell below $300 and durability of RFA fell below 30%. The ICER of S4 versus S3 still remained above $100,000/dQALY even with EGD costs as low as $100 and surveillance frequency of only 1 EGD every 10 years. Conclusion: Initial RFA without subsequent surveillance is the most cost-effective strategy for the management of incidentally-detected BE in young patients.

Colorectal polyps in childhood

Colorectal polyps are a common cause of gastrointestinal bleeding in children. This review updates the information on colorectal polyps and summarizes the recent advances in genetics, diagnosis, and treatment of polyps in the large intestine. A review of recent literature regarding colorectal polyps demonstrates an estimated detected prevalence of 6.1% overall and 12.0% among those with lower gastrointestinal bleeding during pediatric colonoscopy. Non-Caucasian races (e.g., black and Hispanic) are at higher risk for colorectal polyps in childhood. Recent data show juvenile polyps may recur in approximately 45% of children with multiple polyps and 17% of children with solitary polyps. A clinical trial showed that celecoxib, a cyclooxygenase (COX)-2 inhibitor, significantly reduced the number of colorectal polyps in children with familial adenomatous polyposis (FAP). Ethical challenges related to genetic tests for FAP have been newly examined. The utility of novel endoscopic techniques (e.g., enteroscopy) in Peutz-Jeghers Syndrome to prevent intussusception have been newly described. Although colorectal polyps in children are generally benign and easily removed, careful clinical evaluation and ongoing research are needed to identify the small proportion of children at risk for cancer. The current paradigm of using the polyp number at presentation as a primary determinant of subsequent surveillance may be inadequate for many patients.

Eradication of Neuroendocrine Cells Within Barrettʼs Esophagus Using Liquid Nitrogen Spray Cryotherapy

Purpose: Barrett's esophagus (BE) is a pre-malignant condition characterized by goblet cell metaplasia. Case reports demonstrate the presence of neuroendocrine (NE) cells within both Barrett's metaplasia and esophageal adenocarcinoma (EAC). NE cells also can proliferate to form their own tumors within the GI tract, or be present on histologic evaluation of other tumors such as gastric or colonic carcinoma. The association of NE cells with progression to carcinoma is uncharacterized, but their presence is theorized to increase malignant potential. A 48 year old Caucasian male presented for evaluation of heartburn, regurgitation, nocturnal cough and dysphagia to a local gastroenterologist. He was diagnosed with GERD and BE, and was started on a proton pump inhibitor (PPI). Due to persistent symptoms, he was referred to our center. 48 hour wireless esophageal pH monitoring off PPI confirmed upright and supine acid reflux. High resolution manometry demonstrated reduced lower esophageal sphincter resting pressure with normal relaxation and peristalsis. A 2.2 cm hiatal hernia was appreciated and confirmed on endoscopy, during which additional biopsies of long segment BE (C0M4 by Prague classification) were obtained. Histologic evaluation was notable for goblet cell metaplasia, as well as diffuse NE cell hyperplasia (positive chromogranin stain) with focal proliferation of NE cells, consistent with micronodular hyplasia of enterochromaffin-like (ECL) cells. Despite high dose PPI, the patient had persistent nocturnal cough and regurgitation. Nissen fundoplication was planned. The presence of long segment Barrett's, along with NE cells of unknown malignant potential, generated sufficient concern to recommend pre-surgical endoscopic ablation before altering the esophagogastric junction. The patient underwent 7 total sessions of liquid nitrogen spray cryotherapy (CSA Medical, Baltimore MD) every 6 weeks. During each procedure, all salmon-colored mucosa received 3 cycles of 20 seconds of treatment, per the standard ablation protocol. Repeat endoscopy 6 weeks after the final treatment revealed no visual evidence of residual BE. Therefore, 4 quadrant surveillance biopsies were taken throughout the original segment length. On these and all subsequent surveillance biopsies, histologic evaluation has confirmed the absence of both goblet cell metaplasia and NE cells. The patient has undergone successful Nissen fundoplication, and is doing well off PPI. To our knowledge, this is the first demonstration of successful eradication of NE cells in the gastrointestinal tract with use of liquid nitrogen spray cryotherapy. Further studies are needed to evaluate the role of NE cells in progression of BE to EAC. Disclosure: Dr. Smith - Consultant, CSA Medical, Inc.

Field Evaluation of a Coproantigen Detection Test for Fascioliasis Diagnosis and Surveillance in Human Hyperendemic Areas of Andean Countries

BackgroundEmergence of human fascioliasis prompted a worldwide control initiative including a pilot study in a few countries. Two hyperendemic areas were chosen: Huacullani, Northern Altiplano, Bolivia, representing the Altiplanic transmission pattern with high prevalences and intensities; Cajamarca valley, Peru, representing the valley pattern with high prevalences but low intensities. Coprological sample collection, transport and study procedures were analyzed to improve individual diagnosis and subsequent treatments and surveillance activities. Therefore, a coproantigen-detection technique (MM3-COPRO ELISA) was evaluated, using classical techniques for egg detection for comparison.Methodology and FindingsA total of 436 and 362 stool samples from schoolchildren of Huacullani and Cajamarca, respectively, were used. Positive samples from Huacullani were 24.77% using the MM3-COPRO technique, and 21.56% using Kato-Katz. Positive samples from Cajamarca were 11.05% using MM3-COPRO, and 5.24% using rapid sedimentation and Kato-Katz. In Huacullani, using Kato-Katz as gold standard, sensitivity and specificity were 94.68% and 98.48%, respectively, and using Kato-Katz and COPRO-ELISA test together, they were 95.68% and 100%. In Cajamarca, using rapid sedimentation and Kato-Katz together, results were 94.73% and 93.58%, and using rapid sedimentation, Kato-Katz and copro-ELISA together, they were 97.56% and 100%, respectively. There was no correlation between coproantigen detection by optical density (OD) and infection intensity by eggs per gram of feces (epg) in Cajamarca low burden cases (<400 epg), nor in Huacullani high burden cases (≥400 epg), although there was in Huacullani low burden cases (<400 epg). Six cases of egg emission appeared negative by MM3-COPRO, including one with a high egg count (1248 epg).ConclusionsThe coproantigen-detection test allows for high sensitivity and specificity, fast large mass screening capacity, detection in the chronic phase, early detection of treatment failure or reinfection in post-treated subjects, and usefulness in surveillance programs. However, this technique falls short when evaluating the fluke burden on its own.

Many Patients Who Undergo Surgery for Colorectal Cancer Receive Surveillance Colonoscopies Earlier Than Recommended by Guidelines

Patients treated with surgery for colorectal cancer (CRC) should undergo colonoscopy examinations 1, 4, and 9 years later, to check for cancer recurrence. We investigated the use patterns of surveillance colonoscopies among Medicare patients. We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients who underwent curative surgery for colorectal cancer from 1992 to 2005 and analyzed the timing of the first 3 colonoscopies after surgery. Early surveillance colonoscopy was defined as a colonoscopy, for no reason other than surveillance, within 3 months to 2 years after a colonoscopy examination with normal results. Approximately 32.1% and 27.3% of patients with normal results from their first and second colonoscopies, respectively, underwent subsequent surveillance colonoscopies within 2 years (earlier than recommended). Of patients who were older than 80 years at their first colonoscopy, 23.6% underwent a repeat procedure within 2 years for no clear indication. In multivariable analysis, early surveillance colonoscopy was not associated with sex, race, or patients' level of education. There was significant regional variation in early surveillance colonoscopies among the Surveillance, Epidemiology, and End Results regions. There was a significant trend toward reduced occurrence of second early surveillance colonoscopies. Many Medicare enrollees who have undergone curative resection for colorectal cancer undergo surveillance colonoscopy more frequently than recommended by the guidelines. Reducing overuse could free limited resources for appropriate colonoscopy examinations of inadequately screened populations.

Glomangiopericytoma (sinonasal-type haemangiopericytoma)

Glomangiopericytoma is a rare sinonasal tumour of perivascular myoid phenotype, which accounts for less than 1 per cent of all sinonasal tumours. Discussion of the clinical presentation, histopathological features and advances in the management of sinonasal and skull base glomangiopericytoma. A 32-year-old woman presented with worsening nasal obstruction, anosmia, severe frontal headaches and right-sided proptosis. Radiographic and endoscopic examination revealed a right-sided, vascular mass involving the nasal cavity, paranasal sinuses and anterior skull base. Histopathological features were consistent with a glomangiopericytoma. Complete endoscopic resection with free margins was achieved. Glomangiopericytomas are rare, vascular, sinonasal tumours. Successful management depends on complete resection, traditionally achieved via an open approach. However, recent advances in endoscopic surgical approaches have enabled complete endoscopic resection of these tumours, minimising morbidity and facilitating subsequent surveillance of the operative site.

CORRUPTION SURVEY IN CROATIA: SURVEY CONFIDENTIALITY AND TRUST IN INSTITUTIONS

In an attempt to explore the linkages between corruption surveys, underreporting corruption experiences and causes of reluctance to report corruption, this paper provides insight into solutions applied to mitigate the underreporting risks in surveying corruption experiences in Croatia. Based on the Survey on use of public services and public integrity in Croatia 2010, the issue of underreporting corruption is assessed with a two-fold approach. The study first discusses the survey methodology applied, where the main concerns were the willingness of respondents to report corruption and their perceptions regarding risk of personal data misuse. Potential reluctance to admit involvement in corruption as a criminal act might be driven by a fear of subsequent surveillance or investigation. Further, we investigate the concerns expressed by respondents regarding the misuse of data and about protecting anonymity. Survey data were used to analyze citizens' attitudes and reasons for (not) reporting crime to official institutions. The analysis focuses on reporting corruption experiences, both formally and informally. The findings show a very high level of citizens' opportunism and lack of public trust in institutions that might impede anti-corruption efforts in Croatia.

The Utility of Serum Thyroglobulin Measurement at the Time of Remnant Ablation for Predicting Disease-Free Status in Patients with Differentiated Thyroid Cancer: A Meta-Analysis Involving 3947 Patients

Decisions regarding initial therapy and subsequent surveillance in patients with differentiated thyroid cancer (DTC) depend upon an accurate assessment of the risk of persistent or recurrent disease. The objective of this study was to examine the predictive value of a single measurement of serum thyroglobulin (Tg) just before radioiodine remnant ablation (preablation Tg) on subsequent disease-free status. Sources included MEDLINE and BIOSYS databases between January 1996 and June 2011 as well as data from the author's tertiary-care medical center. Included studies reported preablation Tg values and the outcome of initial therapy at surveillance testing or during the course of long-term follow-up. Two investigators independently extracted data and rated study quality using the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews-2 (QUADAS-2) tool. Fifteen studies involving 3947 patients with DTC were included. Seventy percent of patients had preablation Tg values lower than the threshold value being examined. The negative predictive value (NPV) of a preablation Tg below threshold was 94.2 (95% confidence interval = 92.8-95.3) for an absence of biochemical or structural evidence of disease at initial surveillance or subsequent follow-up. The summary receiver operator characteristic curve based on a bivariate mixed-effects binomial regression model showed a clustering of studies using a preablation Tg below 10 ng/ml near the summary point of optimal test sensitivity and specificity. Preablation Tg testing is a readily available and inexpensive tool with a high NPV for future disease-free status. A low preablation Tg should be considered a favorable risk factor in patients with DTC. Further study is required to determine whether a low preablation Tg may be used to select patients for whom radioiodine remnant ablation can be avoided.

Methylcap-seq reveals novel DNA methylation markers for the diagnosis and recurrence prediction of bladder cancer in a Chinese population.

PurposeThere is a need to supplement or supplant the conventional diagnostic tools, namely, cystoscopy and B-type ultrasound, for bladder cancer (BC). We aimed to identify novel DNA methylation markers for BC through genome-wide profiling of BC cell lines and subsequent methylation-specific PCR (MSP) screening of clinical urine samples.Experimental DesignThe methyl-DNA binding domain (MBD) capture technique, methylCap/seq, was performed to screen for specific hypermethylated CpG islands in two BC cell lines (5637 and T24). The top one hundred hypermethylated targets were sequentially screened by MSP in urine samples to gradually narrow the target number and optimize the composition of the diagnostic panel. The diagnostic performance of the obtained panel was evaluated in different clinical scenarios.ResultsA total of 1,627 hypermethylated promoter targets in the BC cell lines was identified by Illumina sequencing. The top 104 hypermethylated targets were reduced to eight genes (VAX1, KCNV1, ECEL1, TMEM26, TAL1, PROX1, SLC6A20, and LMX1A) after the urine DNA screening in a small sample size of 8 normal control and 18 BC subjects. Validation in an independent sample of 212 BC patients enabled the optimization of five methylation targets, including VAX1, KCNV1, TAL1, PPOX1, and CFTR, which was obtained in our previous study, for BC diagnosis with a sensitivity and specificity of 88.68% and 87.25%, respectively. In addition, the methylation of VAX1 and LMX1A was found to be associated with BC recurrence.ConclusionsWe identified a promising diagnostic marker panel for early non-invasive detection and subsequent BC surveillance.

Improving poisoning diagnosis and surveillance of street pesticides

An effective surveillance system is required to reduce pesticide exposures and poisonings, especially from street pesticides (illegal, unlabelled, and decanted agricultural pesticides used predominately for urban household purposes). Poisoning from any pesticide class, not only organophosphates, constitutes a medically notifiable condition in South Africa. Current practice, however, is to report only organophosphate cases, resulting in severe under-reporting. The lack of data concerning the link between poisonings and street pesticides has led to the mistaken assumption that urban populations are not at risk from significant pesticide exposures and poisonings. Without accurate statistics, healthcare professionals and policy makers are unaware of the contribution of street pesticide poisonings to the overall health burden. Accurate diagnosis is a prerequisite for notification and subsequent surveillance. An algorithm has been developed to enable healthcare professionals to improve the diagnosis and notification of pesticide poisonings.