Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett's esophagus neoplasia with histopathology correlation.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.

BACKGROUND AND STUDY AIMS: The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. PATIENTS AND METHODS: Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. RESULTS: Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). CONCLUSIONS: In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

The combination of stricture dilation, endoscopic needle aspiration, and biliary brushings significantly improves diagnostic yield from malignant bile duct strictures.

BACKGROUND: Brush cytology, routinely performed at ERCP to assess malignant-appearing biliary strictures, is limited by relatively low sensitivity and negative predictive value. This study assessed whether the combination of stricture dilation, endoscopic needle aspiration, and biliary brushing improves diagnostic yield. METHODS: In a prospective nonrandomized study, 46 consecutive patients were evaluated with malignant-appearing biliary strictures at ERCP. Twenty-four patients (Group A) underwent standard brush cytology alone and 22 patients (Group B) underwent stricture dilatation to 10F, endoscopic needle aspiration, and subsequent biliary brushing by using the Howell biliary system. The diagnostic yields for both techniques were compared. RESULTS: Of the 46 patients, 34 had proven malignant strictures (14 Group A, 20 Group B). Compared with brushing alone, the combination of stricture dilatation, endoscopic needle aspiration, and subsequent biliary brushing significantly increased both the sensitivity (57% vs. 85%, p < 0.02) and specificity (80% vs. 100%, p < 0.02) of cytology with positive brushings in all patients with pancreatic or gallbladder carcinoma. CONCLUSIONS: The combination of stricture dilation, endoscopic needle aspiration, and biliary brushing significantly improves diagnostic yield for malignant bile duct strictures and may particularly be of benefit for extrinsic strictures caused by pancreatic or gallbladder carcinoma.

Clinical features of microsporidiosis in patients with AIDS.

Microsporidia are protozoan parasites responsible for significant gastrointestinal disease in patients infected with human immunodeficiency virus. We report the clinical features of 20 patients with chronic diarrhea for whom microsporidian spores were identified by modified trichrome staining of stool smears and confirmed by biopsy and/or electron microscopy of stool. Of the 18 microsporidian protozoa identified to the species level, 14 (78%) were Enterocytozoon bieneusi and four (22%) were Septata intestinalis. The mean CD4 count in these patients was 35 +/- 29 cells/mm3. Parameters of absorption, specifically absorption of fat and D-xylose, and levels of zinc were strikingly abnormal in patients who were tested. Treatment with albendazole led to clinical responses in six of 10 patients, and dietary manipulation resulted in clinical improvement in eight of nine patients. We recommended that patients with chronic, intermittent diarrhea and CD4 counts of < 100 cells/mm3 be further evaluated for microsporidia by modified trichrome staining of stool and light and electron microscopy of small bowel biopsy specimens. Antiprotozoal therapies are currently experimental, but some patients who have been treated with these therapies have dramatic responses. We also recommend that special attention be paid to the measurement of parameters of absorption with appropriate modification of diet.

Evaluation of a serologic marker, CA19-9, in the diagnosis of pancreatic cancer.

STUDY OBJECTIVE: To determine the utility of the serologic marker CA19-9 in the diagnosis of pancreatic cancer in patients suspected of having a pancreatic disorder. DESIGN: Blinded study of frozen pedigreed serum samples collected at time of diagnostic evaluation with follow-up review at a mean of 8 years. SETTING: A general university teaching hospital serving both primary and referral patient populations. MEASUREMENTS AND MAIN RESULTS: Sera collected prospectively from 1978 to 1980 from 261 patients undergoing imaging studies of the pancreas (ultrasound, computed tomography, endoscopic retrograde cholangiopancreatography) for a variety of symptoms were assayed for CA19-9 levels, and the results were compared with earlier determinations of other potential markers for pancreatic cancer. In 54 patients ultimately shown to have pancreatic cancer, the CA19-9 assay showed a sensitivity of 70% with a median value of 349 u/mL (normal less than 70 u/mL) and range, 7.3 to 2,859,964 u/mL, whereas specificity of the marker in this population was 87%. The positive predictive value was 59%, and the negative predictive value was 92%. Results of CA19-9 testing in the small group of patients with definitive staging information showed no difference in sensitivity between patients with local/regional disease (n = 6) and those with distant metastases (n = 14), 50% compared with 71% (P = 0.613). CONCLUSION: CA19-9 was found to be a more sensitive and specific marker of pancreatic cancer than other serologic markers and should be a useful test in the patient with suspected pancreatic disease.

Latent transformed growth-inhibiting factor in human malignant effusions.

An inhibitor of soft agar colony formation by a human breast carcinoma-derived cell line was found to be present in latent form in the majority of cytology-positive human malignant effusions. Prior to dialysis, addition of human malignant effusions resulted in less than 10% alteration in efficiency of colony formation by the BT-20 human breast carcinoma cell line (mean efficiency 1 colony/4.3 cells plated at 14 days; mean colony diameter greater than 0.8 mm). After dialysis (membrane cutoff of 3500 molecular weight), 58 of 70 malignant effusions from patients with a variety of epithelial cell carcinomas resulted in 71% mean inhibition of colony formation (range 19.1-98% inhibition). Similar inhibition of anchorage-independent growth was observed for a human colon cancer-derived cell line (HCT-15) but not for polyoma and murine sarcoma virus-transformed rodent fibroblast lines. The malignant effusion-related transformed cell growth-inhibiting factor (TGIF) was sensitive to heat, sulfhydryl reduction, and protease treatment. TGIF-containing effusion resulted in parallel inhibition of thymidine incorporation in sensitive cell types in vitro. TGIF was precipitable in 28-34% ammonium sulfate with reconstitution of activity after resolubilization. TGIF was partially purified by chromatography on Biogel A-0.5 and Biogel P-100 which yielded two peaks of inhibitory activity. The predominant species had an approximate molecular weight of 110,000 and could be recovered as a single species from DEAE-cellulose at relatively high salt concentrations (0.4 M NaCl). A smaller amount of inhibitory activity was recovered from Biogel P-100 or Biogel P-60 with an apparent molecular weight of 55,000. The higher molecular-weight TGIF which appears to be a dimer of the Mr 55,000 protein is distinguishable from previously described growth-promoting and -inhibiting factors.