Anne E. Rader

Office-Based Unsedated Small-Caliber Endoscopy Is Equivalent to Conventional Sedated Endoscopy in Screening and Surveillance for Barrett's Esophagus: A Randomized and Blinded Comparison

OBJECTIVES:A major limitation to screening and surveillance of Barretts esophagus is the complexity, expense, and risk associated with sedation for upper endoscopy. This study examines the feasibility, accuracy, and patient acceptability of office-based unsedated endoscopy as an alternative.METHODS:Of 274 eligible adults scheduled for endoscopic screening for gastroesophageal reflux symptoms or surveillance of Barretts esophagus at a tertiary care center, 121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a randomized crossover study. The two procedures were compared with regard to histological detection of Barretts esophagus and dysplasia and biopsy size. Patients answered questionnaires assessing the tolerability of the procedures.RESULTS:The prevalence of Barretts esophagus was 26% using conventional endoscopy and 30% using unsedated endoscopy (P = 0.503). The level of agreement between the two approaches was “moderate” (κ = 0.591). Each modality detected four cases of low-grade dysplasia with concordance on one case. The tissue samples collected with unsedated endoscopy were smaller than with conventional endoscopy (P < 0.001). The majority of subjects rated their experience with both procedures as being well tolerated with minimal or no difficulty. When asked which procedure they would prefer in the future, 71% (81/114) chose unsedated small-caliber endoscopy.CONCLUSIONS:Office-based unsedated small-caliber endoscopy is technically feasible, well tolerated, and accurate in screening for Barretts esophagus, despite yielding a smaller biopsy specimen. This approach bears the potential to eliminate the infrastructure and cost required for intravenous sedation in this application.

Novel markers of pancreatic adenocarcinoma in fine-needle aspiration: mesothelin and prostate stem cell antigen labeling increases accuracy in cytologically borderline cases.

The interpretation of pancreas fine-needle aspiration (FNA) is extremely difficult given the cytologic overlap of neoplastic and reactive processes. Using serial analysis of gene expression, we have discovered 2 new markers of pancreatic adenocarcinoma, mesothelin and prostate stem cell antigen (PSCA), and confirmed their specificity by immunohistochemical labeling. Here we evaluate the potential contribution of immunohistochemical labeling of mesothelin and PSCA to the interpretation of pancreas FNAs. Thirty pancreas FNAs with follow-up data were reviewed. Unstained cell block sections from these aspirates labeled for mesothelin and PSCA using immunohistochemistry were compared with initial cytologic diagnoses and with follow-up diagnoses. On follow-up, 19 patients proved to have cancer, and 11 did not. Initial cytologic diagnosis of malignancy correlated with carcinoma on follow-up in 12 of 12 cases, and initial benign cytologic diagnosis correlated with benign follow-up in 8 of 9 cases (sensitivity, 92%; specificity, 100%). Six of the 9 patients with suspicious cytology were found to have a carcinoma on follow-up. PSCA labeling was present in 16 of the 19 patients who ultimately were proven to have carcinoma; PSCA labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 84%; specificity, 91%). Mesothelin labeling was present in 13 of the 19 patients who ultimately were proven to have carcinoma; mesothelin labeling was absent in 10 of the 11 lesions proven to be benign (sensitivity, 68%; specificity, 91%). Five of the 6 cytologically suspicious cases with malignant follow-up labeled for either PSCA or mesothelin (83%), and 2 of the 6 cases labeled for both markers. None of the 3 suspicious cases with benign follow-up labeled for either PSCA or mesothelin. Increasingly, molecular techniques are identifying potential cancer markers that may have diagnostic utility. In this study, immunohistochemical labeling for 2 of these markers, PSCA and mesothelin, appears highly specific for pancreatic adenocarcinoma in FNA specimens and useful in categorizing cytologically suspicious lesions.

K-ras, p53, and DPC4 (MAD4) Alterations in Fine-Needle Aspirates of the Pancreas A Molecular Panel Correlates With and Supplements Cytologic Diagnosis

Between January 1997 and February 2000, 101 fine-needle pancreatic aspirates were obtained. After a cytologic diagnosis was made, possible molecular alterations were determined on the 94 aspirates with adequate tissue using a molecular panel (K-ras, p53, and DPC4 [MAD4] genes). The 94 aspirates were categorized as follows: diagnostic of adenocarcinoma, 48 (51%); atypical (suggestive of but not diagnostic of adenocarcinoma), 19 (20%); negative for adenocarcinoma, 25 (2 7%); diagnostic of a neoplasm other than adenocarcinoma, 2 (2%). Clinical follow-up revealed that 3 patients (12%) with negative cytologic diagnoses and 12 patients (63%) with atypical cytologic diagnoses had adenocarcinoma. Of 63 with a final diagnosis of adenocarcinoma, 42 (67%) had an alteration in at least 1 of the genes analyzed. In contrast, only 2 (6%) of 31 patients without adenocarcinoma had an alteration in 1 gene on the panel. Overall, the molecular analyses supported the diagnosis of adenocarcinoma in 6 (32%) of 19 aspirates originally diagnosed as atypical by cytology alone. A molecular panel that includes the K-ras, p53, and DPC4 (MAD4) genes correlates with and can supplement traditional cytologic diagnosis of pancreatic fine-needle aspirates.

Cytological screening for Barrett's esophagus using a prototype flexible mesh catheter

The current cost of endoscopically screening patients with gastroesophageal reflux disease (GERD) and Barretts esophagus (BE) is considerable. A nonendoscopic device that allows for screening of these patients would offer significant cost savings. This pilot study evaluates the utility of cytologically diagnosing BE using a prototype flexible mesh catheter. Patients with known BE undergoing indicated surveillance endoscopy were enrolled in the study. Cytology specimens were obtained using a prototype flexible catheter and were evaluated for the presence of glandular cells, goblet cells, squamous cells, inflammation, and dysplasia. Eleven patients with BE were enrolled in the study. None of the patients experienced complications. Specimens from eight patients (73%) were adequate for evaluation and seven of these patients (87.5%) had goblet cells diagnostic for BE. In conclusion, flexible mesh catheters potentially offer a sensitive, inexpensive, and minimally invasive approach to evaluating patients with GERD and BE.

Aspiration cytology and core biopsy of a carcinoid tumor arising in a retrorectal cyst: A case report

Retrorectal cysts are uncommon lesions of uncertain histogenesis, and primary carcinoid tumors arising in retrorectal cysts are extremely rare. We present the case of a 52‐yr‐old man who had a 22‐cm partially cystic, partially solid mass in the presacral space. A computed tomography‐guided fine‐needle aspiration of the mass was performed. The smears contained abundant keratinous debris and rare groups of tumor cells. The tumor cells were cuboidal, with slightly granular cytoplasm and centrally located nuclei with speckled chromatin and inconspicuous nucleoli. Immunocytochemical analysis revealed strong reactivity for chromogranin and keratin, and focal reactivity for synaptophysin and neuron‐specific enolase. The cytological diagnosis of a carcinoid arising in a tail‐gut cyst was confirmed histologically.

Merkel cell carcinoma in a malignant pleural effusion : Case report

Background Merkel cell (neuroendocrine) carcinoma is a small round blue cell malignant neoplasm that primarily presents in the skin. The diagnosis of Merkel cell carcinoma in a pleural fluid is challenging because of the morphological similarity to many other malignant neoplasms. Immunohistochemical stains can be essential to establish the diagnosis of Merkel cell carcinoma. Case presentation A 77 year-old woman presented with a mass in her right buttock thought clinically to be a boil or sebaceous cyst. Upon histopathologic review including immunohistochemical analysis, a diagnosis of Merkel cell carcinoma was rendered. Wide-excision and sentinel lymph node biopsy revealed negative margins and no evidence of metastasis. Ten months later she complained of bone pain and a bone scan revealed multiple lesions. An abdominal CT scan revealed a T4 vertebral mass and local radiotherapy was administered. Two months later the patient presented with shortness of breath. A chest radiograph showed an effusion and thoracentesis was performed. The fluid was confirmed to contain metastatic Merkel cell carcinoma by cytology and immunohistochemical analysis. Conclusions Merkel cell carcinoma is an aggressive neoplasm that can, despite careful surgical management, occasionally present as a malignant pleural effusion in a relatively short time period. Immunohistochemical analysis can aid in confirming this rare outcome.