Accuracy of real-time vs. blinded offline diagnosis of neoplastic colorectal polyps using probe-based confocal laser endomicroscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Probe-based confocal laser endomicroscopy (pCLE) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures. Most studies have evaluated offline interpretation of pCLE images. In clinical practice, real-time interpretation is necessary to assist decision-making during the procedure. The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies. PATIENTS AND METHODS: pCLE was performed in patients undergoing screening and surveillance colonoscopy. Once a polyp had been identified, one endoscopist analyzed pCLE images during the procedure and made a provisional "real-time" diagnosis. Saved video recordings were de-identified, randomized, and reviewed "offline" 1 month later by the same endoscopist, who was blinded to the original diagnoses. RESULTS: Images from a total of 154 polyps were recorded (80 neoplastic, 74 non-neoplastic). The overall accuracy of real-time pCLE diagnosis (accuracy 79%, sensitivity 81%, specificity 76%) and offline pCLE diagnosis (83%, 88%, and 77%, respectively) for all 154 polyps were similar. Among polyps < 10 mm in size, the accuracy of real-time interpretation was significantly lower (accuracy 78%, sensitivity 71%, specificity 83%) than that of offline pCLE interpretation (81%, 86%, 78%, respectively). For polyps ≥ 10 mm, the accuracy of pCLE diagnosis in real-time was better (accuracy 85%, sensitivity 90%, specificity 75%) than offline pCLE diagnosis (81%, 97%, and 50%, respectively). CONCLUSIONS: These results suggest that real-time and offline interpretations of pCLE images are moderately accurate. Real-time interpretation is slightly less accurate than offline diagnosis, but overall both are comparable. Additionally, there was contrasting accuracy between the two methods for small and large polyps.

New classification for probe-based confocal laser endomicroscopy in the colon.

BACKGROUND AND AIMS: Probe-based confocal laser endomicroscopy (pCLE; Cellvizio, Mauna Kea Technologies, Paris, France) enables in vivo histology during colonoscopy and may allow endoscopists to make real-time diagnoses. A collaboration of five experts proposed a new pCLE classification for colonic use. The aim of this study was to assess interobserver agreement and accuracy of the new pCLE classification in the colon. PATIENTS AND METHODS: Eligible patients were prospectively investigated by pCLE. A subset of 13 pCLE video sequences was reviewed post hoc for the establishment of a new classification, which comprised three vessel categories and seven crypt categories. All five blinded observers then scored another set of 102 video sequences, using the new classification. Histopathology was used as a reference standard. RESULTS: The interobserver agreements on vessel and crypt architecture were 'fair' with kappa values of 0.29 and 0.27, respectively. When the classification was reduced to neoplasia vs. non-neoplasia (i.e. vessel or crypt type 3), overall agreement became 'moderate' (κ = 0.56). Overall sensitivity and specificity for predicting neoplasia was 66 % and 83 %, respectively. When all observers agreed (69 % of videos), the corresponding figures became 80 % and 95 %. CONCLUSION: A new classification for pCLE in the colon had a 'moderate' interobserver agreement for differentiating neoplasia from non-neoplastic tissue in the colon. The overall accuracy (81 %) for predicting neoplasia was acceptable and became excellent (94 %) when all five observers agreed. Future research should focus on refinement and validation of the classification.

A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection.

BACKGROUND AND STUDY AIMS: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. PATIENTS AND METHODS: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. RESULTS: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). CONCLUSIONS: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.

Interobserver agreement and accuracy among international experts with probe-based confocal laser endomicroscopy in predicting colorectal neoplasia.

BACKGROUND AND STUDY AIMS: A recently developed probe-based, confocal laser endomicroscopy (pCLE) system provides images of surface colonic epithelium in vivo during any endoscopy. Our objective was to assess interobserver agreement, sensitivity, specificity, and overall accuracy in the diagnosis of neoplasia using pCLE. PATIENTS AND METHODS: 53 patients undergoing surveillance and screening colonoscopies were enrolled. A total of 75 lesions, were detected and all were inspected by pCLE prior to sampling or polypectomy. Intravenous fluorescein was used to optimize tissue contrast. Three pCLE users, blinded to histopathologic and endoscopic findings, reviewed the set of video sequences for crypt architecture, vessel architecture, and colorectal neoplasia diagnosis. Histopathologic diagnosis from the corresponding biopsies was the reference gold standard. RESULTS: Of the 75 colorectal lesions, 50 were neoplastic and 25 non-neoplastic. Interobserver agreement was moderate to good for the classification of neoplasia (kappa 0.55, 78 % pairwise agreement), and moderate for vessel architecture (kappa 0.41, 67 % pairwise agreement) and crypt architecture (kappa 0.49, 69 % pairwise agreement). In distinguishing between neoplastic and non-neoplastic lesions, sensitivity, specificity, and accuracy were 76 %, 72 % and 75 %, respectively. When videos of good or excellent quality only were considered, interobserver agreement for classification of neoplasia was higher (kappa 0.83, 92 % pairwise agreement), as were sensitivity (88 %), specificity (89 %), and accuracy (88 %). CONCLUSION: An international collaboration group had moderate to good interobserver agreement using a pCLE system to predict neoplasia, which is acceptable for this study.

New frontiers in therapeutic EUS: dreams, style exercises or actual possibilities.

The term therapeutic endoscopic ultrasound (EUS) refers to direct ultrasound guided placement of pharmaceuticals, devices and biological agents for the purpose of treating a disease or symptoms. The vast majority of EUS procedures in the world are performed for diagnostic purposes, although these lead directly to therapeutic decisions such as whether to treat diseases by local (including endoscopic) resection, surgery or chemotherapy. EUS imaging is providing directions for therapies in different conditions, such as 1) gastrointestinal (GI) diseases including luminal GI malignancies, 2) management of pancreatic pain by performing the celiac plexus block, 3) drainage of obstructed biliary and pancreatic ducts when standard ERCP methods have failed, and 4) lesions surrounding the gut wall, including adjacent organs (pancreas liver, etc) and mediastinum (e.g. non-small cell lung cancer staging). Experimental promising EUS applications include delivery of cytotoxic agents such as chemotherapy, gene therapy, and radioactive seeds. This article will review the diagnostic and therapeutic role of EUS in gastrointestinal as well as extra-intestinal diseases.

Comorbid occurrence of liver and pancreas disease in United States military veterans.

OBJECTIVE: The clinical epidemiology of the comorbidity between liver and pancreas disease is unknown. The Patient Treatment File of the Department of Veterans Affairs contains the computerized records of all inpatients treated in 172 Department of Veterans Affairs hospitals distributed throughout the United States. This large database offers a unique opportunity to study the epidemiology of liver-pancreas comorbidity (LPC). METHODS: In a case-control study, 6,393 LPC cases were compared to 34,513 controls with alcoholic liver disease and liver cirrhosis alone and 68,038 controls without liver or pancreas disease. Multivariate logistic regression analysis was used to assess the joint influence of multiple risk factors on the occurrence of LPC. RESULTS: LPC occurred in 15.6% of patients with alcoholic liver disease and liver cirrhosis identified in the Patient Treatment File between 1990 and 1993. Compared to controls with liver disease alone, LPC cases were characterized by younger age (odds ratio = 0.88 per age decade, CI = 0.86-0.90) and African American (2.33, 2.18-2.48) or Hispanic (1.24, 1.12-1.38) ethnicity. Compared to controls with neither liver nor pancreas disease, LPC cases were characterized by male gender (1.67, 1.28-2.17), African American (1.41, 1.32-1.50) or Hispanic (2.04, 1.82-2.30) ethnicity, more frequent history of alcoholism (29.5, 26.7-32.6), and being divorced (1.35, 1.26-1.44). CONCLUSIONS: Comorbidity of liver and pancreas disease is relatively common in the veteran population. Such patients are more frequently divorced and of African American or Hispanic ethnicity, and present with a history of excessive alcoholism at a relatively young age.

Medical diagnoses and procedures associated with clostridium difficile colitis.

OBJECTIVES: The aim of this study was to examine the associations of Clostridium difficile colitis with other comorbid conditions and procedural interventions among hospitalized patients. METHODS: The Patient Treatment File of the Department of Veterans Affairs contains the computerized records of all inpatients treated in 172 Veterans Affairs hospitals distributed throughout the United States. The computerized medical records of 15,091 cases with C. difficile colitis and 61,931 controls without the diagnosis were extracted from the annual files between 1993 and 1998. In a multivariable logistic regression, the occurrence of C. difficile colitis served as outcome variable, whereas the occurrences of other diagnoses or procedures served as predictor variables. RESULTS: The total numbers of diagnoses in the case and control group were 136,840 and 465,972, respectively. The numbers of procedures were 75,479 and 129,612, respectively. C. difficile colitis was significantly associated with HIV infection, candidiasis, malignant neoplasm and chemotherapy, malnutrition, pneumonia, aspiration pneumonitis, intestinal obstruction, diverticulitis, renal failure, urinary tract infection, decubitus, and osteomyelitis. Interventional procedures involving the respiratory tract, bone marrow biopsy, arterial and venous catheterization, urinary catheterization, dialysis, gastrostomy tube, and physical therapy were also frequently associated with the development of C. difficile colitis. CONCLUSIONS: These associations reflect the influence of causal relationships (such as the use of antibiotics and chemotherapy), an increased risk of exposure to C. difficile among immobilized bedridden patients with chronic disease states, or a general system failure in patients with end-stage disease. Knowledge of such associations could help to alert physicians to an increased risk of C. difficile colitis among particular groups of susceptible patients.