Collagenous sprue is not always associated with dismal outcomes: a clinicopathological study of 19 patients.

Collagenous sprue is associated with high morbidity; however, the etiology of this disorder is unclear. Data regarding the pathological and clinical manifestations of patients with collagenous sprue are also limited. We, thus, undertook this study to gain insight into the etiology, disease manifestations and outcomes of collagenous sprue. We searched our departmental database (1999-2008) to identify cases of collagenous sprue and to obtain clinical and laboratory data. Small bowel histology, including thickness of subepithelial collagen, intra-epithelial lymphocyte phenotype and results of T-cell clonality assays were evaluated. Nineteen patients (15 women, 4 men, age 22-80 years, mean 57 years) were identified. Seventeen (89%) had celiac disease and two had unclassified sprue; 9 of 17 (53%) celiac disease patients had refractory disease; 5 of 15 (33%) lacked diarrhea (atypical presentation), including 2 of 6 (33%) with active (untreated) celiac disease and 3 of 9 (33%) with refractory celiac disease. Autoimmune disorders were seen in 12 of 19 (63%) patients and microscopic colitis (n=7), lymphocytic gastritis (n=2) or collagenous gastritis (n=2) were seen in nine patients. Subepithelial collagen thickness was mildly (n=6), moderately (n=10), or markedly (n=3) increased and villous atrophy was total (n=13) or subtotal (n=6). Phenotypically aberrant intraepithelial lymphocytes were not detected in any case. Polymerase chain reaction analysis showed a dominant T-cell clone in the only patient with refractory celiac disease type II. Histological improvement occurred in 7 of 11 (64%) patients. Overall, 8 of 19 (42%) responded to gluten-free diet, including 2 of 9 (22%) with refractory celiac disease and 10 responded to immunomodulatory therapy, including 6 of 9 (67%) with refractory celiac disease. Only one patient died from complications of refractory celiac disease. No patient developed lymphoma. The vast majority of our patients with collagenous sprue had celiac disease. Although, many patients required immunomodulatory therapy for symptom control, a subset responded to gluten-free diet alone. In our experience, collagenous sprue patients had relatively good clinical outcomes.

Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett's esophagus.

BACKGROUND: Several types of forceps are available for use in sampling Barrett's esophagus (BE). Few data exist with regard to biopsy quality for histologic assessment. OBJECTIVE: To evaluate sampling quality of 3 different forceps in patients with BE. DESIGN: Single-center, randomized clinical trial. PATIENTS: Consecutive patients with BE undergoing upper endoscopy. INTERVENTIONS: Patients randomized to have biopsy specimens taken with 1 of 3 types of forceps: standard, large capacity, or jumbo. MAIN OUTCOME MEASUREMENTS: Specimen adequacy was defined a priori as a well-oriented biopsy sample 2 mm or greater in diameter and with at least muscularis mucosa present. RESULTS: A total of 65 patients were enrolled and analyzed (standard forceps, n = 21; large-capacity forceps, n = 21; jumbo forceps, n = 23). Compared with jumbo forceps, a significantly higher proportion of biopsy samples with large-capacity forceps were adequate (37.8% vs 25.2%, P = .002). Of the standard forceps biopsy samples, 31.9% were adequate, which was not significantly different from specimens taken with large-capacity (P = .20) or jumbo (P = .09) forceps. Biopsy specimens taken with jumbo forceps had the largest diameter (median, 3.0 mm vs 2.5 mm [standard] vs 2.8 mm [large capacity]; P = .0001). However, jumbo forceps had the lowest proportion of specimens that were well oriented (overall P = .001). LIMITATIONS: Heterogeneous patient population precluded dysplasia detection analyses. CONCLUSIONS: Our results challenge the requirement of jumbo forceps and therapeutic endoscopes to properly perform the Seattle protocol. We found that standard and large-capacity forceps used with standard upper endoscopes produced biopsy samples at least as adequate as those obtained with jumbo forceps and therapeutic endoscopes in patients with BE.

Food group intake and risk of subtypes of esophageal and gastric cancer.

Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multicenter, population-based case-control study in Connecticut, New Jersey and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73) and noncardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and noncardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma.

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.

Scalloping of duodenal mucosa in Crohn's disease.

Scalloping of the duodenal mucosal folds is an endoscopic finding of small bowel mucosal pathology that is generally due to villous atrophy. Though it can be seen in many disease processes, it is most commonly associated with celiac disease. We report three patients with scalloping of duodenal folds and histologic confirmation of villous atrophy due to Crohn's disease. All patients had negative celiac serologies and two had positive markers for Crohn's disease (anti-Saccharomyces cerevisiae antibodies). Patients had either ileitis or ileocolitis in addition to duodenal abnormalities. These cases illustrate that scalloping can occur in the duodenum in Crohn's disease.

Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancers: classification tree analysis.

PURPOSE: Although risk factors for squamous cell carcinoma of the esophagus and adenocarcinomas of the esophagus (EA), gastric cardia (GC), and other (noncardia) gastric (OG) sites have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancers. METHODS: We used classification tree analysis to analyze data from a population-based case-control study (1095 cases, 687 controls) conducted in Connecticut, New Jersey, and western Washington State. RESULTS: Frequency of reported gastroesophageal reflux disease symptoms was the most important risk stratification factor for EA, GC, and OG, with dietary factors (EA, OG), smoking (EA, GC), wine intake (GC, OG), age (OG), and income (OG) appearing to modify the risk of these cancer sites. For esophageal squamous cell carcinoma, smoking was the most important risk stratification factor, with gastroesophageal reflux disease, income, race, noncitrus fruit, and energy intakes further modifying risk. CONCLUSION: Various combinations of risk factors appear to interact to affect risk of each cancer subtype. Replication of these data mining analyses are required before suggesting causal pathways; however, the classification tree results are useful in partitioning risk and mapping multilevel interactions among risk variables.

Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer.

PURPOSE: To carry out pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. METHODS: We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. RESULTS: PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing gastroesophageal reflux disease (GERD)/body mass index (BMI) score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. CONCLUSIONS: PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, whereas fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.

RAGE signaling significantly impacts tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma.

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is a cell surface receptor implicated in tumor cell proliferation and migration. We hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor growth in murine models of colorectal carcinoma. MATERIALS AND METHODS: Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the C57BL/6 background to generate Apc (1638N/+)/Rage (-/-) mice. Metastasis: BALB/c mice underwent portal vein injection with CT26 cells (syngeneic) and received daily soluble (s)RAGE or vehicle. Rage (-/-) mice and Rage (+/+) controls underwent portal vein injection with MC38 cells (syngeneic). Rage (+/+) mice underwent portal vein injection with MC38 cells after stable transfection with full-length RAGE or mock transfection control. RESULTS: Tumorigenesis: Apc (1638N/+)/Rage (-/-) mice had reduced tumor incidence, size, and histopathologic grade. Metastasis: Pharmacological blockade of RAGE with sRAGE or genetic deletion of Rage reduced hepatic tumor incidence, nodules, and burden. Gain of function by transfection with full-length RAGE increased hepatic tumor burden compared to vector control MC38 cells. CONCLUSION: RAGE signaling plays an important role in tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma. Further work is needed to target the ligand-RAGE axis for possible prophylaxis and treatment of primary and metastatic colorectal carcinoma.

Pancreatic cancer screening in a prospective cohort of high-risk patients: a comprehensive strategy of imaging and genetics.

PURPOSE: Pancreatic cancer is a virtually uniformly fatal disease. We aimed to determine if screening to identify curable neoplasms is effective when offered to patients at high risk. EXPERIMENTAL DESIGN: Patients at high risk of pancreatic cancer were prospectively enrolled into a screening program. Endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and genetic testing were offered by a multidisciplinary team according to each patient's risk. RESULTS: Fifty-one patients in 43 families were enrolled, with mean age of 52 years, 35% of whom were male. Of these patients, 31 underwent EUS and 33 MRI. EUS revealed two patients with pancreatic cancer (one resectable, one metastatic), five with intraductal papillary mucinous neoplasms (IPMN), seven with cysts, and six with parenchymal changes. Five had pancreatic surgery (one total pancreatectomy for pancreatic cancer, three distal and one central pancreatectomy for pancreatic intraepithelial neoplasia 2 and IPMN). A total of 24 (47%) had genetic testing (19 for BRCA1/2 mutations, 4 for CDKN2A, 1 for MLH1/MSH2) and 7 were positive for BRCA1/2 mutations. Four extrapancreatic neoplasms were found: two ovarian cancers on prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy, one carcinoid, and one papillary thyroid carcinoma. Overall, 6 (12%) of the 51 patients had neoplastic lesions in the pancreas and 9 (18%) had neoplasms in any location. All were on the initial round of screening. All patients remain alive and without complications of screening. CONCLUSIONS: Pancreatic cancer screening for high-risk patients with a comprehensive strategy of imaging and genetics is effective and identifies curable neoplasms that can be resected. Ongoing study will better define who will benefit from screening and what screening strategy will be the most effective.

An unusual case of colonic mixed adenoendocrine carcinoma: collision versus composite tumor. A case report and review of the literature.

We report a case of collision tumor of the cecum in a 50-year-old woman and discuss the morphological criteria used for classifying mixed glandular-endocrine neoplasms of the digestive tract in a large series of reported cases. The cecal tumor showed clear geographic polarization, with no admixture or transition of the 2 neoplastic components. A lymph nodal metastatic deposit contained both tumors. Immunohistochemical stainings were consistent with the carcinomatous and carcinoidal nature of the 2 neoplasms, except for a minute area of carcinoembryonic antigen positivity in the carcinoid. A review of the literature shows that many mixed glandular-endocrine tumors of the digestive tract escape precise classification using established morphological criteria. Collision and composite tumors can share common histological and immunohistochemical features, including polyclonal metastases and carcinoembryonic antigen expression in the carcinoidal area. Mixed tumors of the cecum showing a collision-like morphology appear to behave more aggressively than other colonic adenoendocrine carcinomas.

Utility in clinical practice of immunoglobulin a anti-tissue transglutaminase antibody for the diagnosis of celiac disease.

BACKGROUND & AIMS: The diagnosis of celiac disease often relies on the anti-tissue transglutaminase (tTG) antibody test. The aim of this study was to evaluate its sensitivity and specificity in clinical practice with the use of commercial laboratories, in which the test characteristics might differ from research laboratories. METHODS: We identified 122 patients with suspected celiac disease who had anti-tTG antibody serologies as well as upper endoscopy with duodenal biopsies. Those with celiac disease were classified as either classic (with diarrhea or other symptoms of malabsorption) or silent (asymptomatic). Biopsies from celiac disease patients were classified as either partial (Marsh IIIA) or total (Marsh IIIB or IIIC) villous atrophy. RESULTS: The overall sensitivity, specificity, and positive and negative predictive values of the anti-tTG antibody test were 70.6%, 65.0%, 91.1%, and 30.2%, respectively. The sensitivity was 90.0% for patients with total villous atrophy and 42.3% for patients with partial villous atrophy (P < .0001). There were differences in both sensitivity and specificity between the 2 most commonly used commercial laboratories. The sensitivity for Lab #1 was 40.0% versus 86.4% for Lab #2 (P < .0001). The specificity for Lab #1 was 100.0%, and it was 41.7% for Lab #2 (P = .02). CONCLUSIONS: The sensitivity of the anti-tTG antibody in clinical practice is not as high as previously reported in research laboratories. The sensitivity is significantly lower in patients with partial villous atrophy. There is also significant variability in test characteristics among major commercial laboratories in the United States. These results need to be confirmed in prospective studies.

Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis.

We have observed expansions of intraepithelial lymphocytes in duodenal biopsies from patients with Helicobacter pylori gastritis. This study was undertaken to prospectively evaluate, unselected, paired gastric and duodenal biopsies from 50 patients with H. pylori gastritis and a comparison group of 30 patients with other types of gastritis (10 autoimmune and 20 reactive) to: (1) quantify duodenal intraepithelial lymphocytes, determine their distribution patterns, epithelial location, and phenotype, and (2) correlate the intraepithelial lymphocyte elevations with various features of gastric and duodenal pathology. Intraepithelial lymphocytes were analyzed with antibodies including CD3, CD8, and TIA-1. A stain for H. pylori was performed on all gastric and duodenal biopsies. Duodenal intraepithelial lymphocytes from patients with H. pylori gastritis (using CD3) ranged from 3 to 42 lymphocytes/100 epithelial cells (mean 18.5) compared to 3 to 18 lymphocytes/100 epithelial cells (mean 6.6) in the comparison group. Intraepithelial lymphocyte elevations were seen in 44% of the duodenal biopsies from patients with H. pylori gastritis (using CD3). Significant differences in the intraepithelial lymphocyte counts between patients with H. pylori gastritis and the comparison group were seen for all three T-cell antigens (P<0.001 for CD3 and CD8 and P<0.002 for TIA-1). Duodenal intraepithelial lymphocytes in the H. pylori+ cases had a latent cytotoxic phenotype, H. pylori was not visualized in any of the duodenal biopsies from patients with H. pylori gastritis, and no patient had clinical evidence of celiac disease. Our study highlights frequent duodenal intraepithelial lymphocytosis in individuals with H. pylori gastritis and the lymphocyte distribution patterns (and numbers) overlapped with those described for celiac disease patients. H. pylori gastritis must be considered as a possible explanation for duodenal intraepithelial lymphocytosis with normal villous architecture, especially when lymphocytosis is patchy, intraepithelial lymphocytes display a 'latent' cytotoxic phenotype, and the clinical findings and serologic profile does not fit celiac disease.

EUS followed by EMR for staging of high-grade dysplasia and early cancer in Barrett's esophagus.

BACKGROUND: Accurate staging of high-grade dysplasia and of early cancer in Barrett's esophagus is important in the selection of patients for endoscopic therapy. METHODS: Patients with Barrett's esophagus and biopsy specimen proven high-grade dysplasia and adenocarcinoma in focal nodular lesions or in endoscopically unapparent flat lesions in short-segment Barrett's esophagus were initially staged with EUS. In patients with disease limited to the mucosa on EUS, cap-assisted EMR was performed. The depth of tumor invasion on EMR specimens was classified in a similar manner to squamous-cell cancer of the esophagus: m1 (epithelial layer, dysplasia), m2 (lamina propria invasion), m3 (muscularis mucosae invasion), sm (submucosal invasion). RESULTS: EUS was performed in 48 consecutive patients (27 with focal nodular lesions and 21 with microscopic lesions), and submucosal invasion was diagnosed in 8 (confirmed in 7/8 at surgery). EMR was carried out in the remaining 40 patients without significant complications. In the 25 patients with high-grade dysplasia on prior biopsy specimens, EMR confirmed m1 disease in 19; whereas in 6 (24%), invasive adenocarcinoma was detected (to m2 in 4; to m3 in 2). In the 15 patients with invasive cancer on prior biopsy specimens and staged as intramucosal cancer on EUS, intramucosal carcinoma was confirmed in 9 (m2 in 3; m3 in 6); whereas, in 6 patients (40%), submucosal invasion was found. Overall, EUS provided accurate staging in 41/48 patients (85%) with one patient overstaged and 6 patients understaged compared with pathologic staging obtained by surgery or EMR. Of the 34 patients with m1 to m3 staging after EMR, 29 were treated endoscopically and had no evidence of cancer after a mean follow-up of 22.9 months(standard deviation 9.2 months). CONCLUSIONS: EMR provides pathologic staging information that, in addition, may be helpful after EUS if a stage-determined approach is used in the management of high-grade dysplasia and of early cancer in Barrett's esophagus. EMR may be particularly useful for staging of focal nodules or in short-segment Barrett's esophagus with microscopic lesions when endoscopic therapy is an option.

The adrenal gland in AIDS.

The adrenal gland has been known to be a common site of opportunistic infections and tumors that define the acquired immunodeficiency syndrome (AIDS) ever since the first autopsy data were published. We have examined the adrenal glands of 66 AIDS patients autopsied in New York City and tabulated and graded the findings in an attempt to estimate the likelihood of adrenal insufficiency developing on the basis of these lesions. AIDSdefining conditions were found in the adrenal glands of 56% of patients, primarily opportunistic infections (53%) and much less frequently neoplasms (3%). Cytomegaloviral (CMV) infection was by far the most common type (42%), followed by mycobacterial (8%) and fungal infections (3%). There was one case eachof Kaposi's sarcoma and lymphoma. Total necrosis of adrenal cortex was restricted to 2 cases of tuberculosis. CMV adrenalitis, although the most common infection and often associated with necrosis, never resulted in more than 30% destruction of the cortex. We conclude that although histopathological evidence of adrenal disease is common in AIDS, most such lesions are not sufficiently extensive to result in adrenal insufficiency. In contrast to previous reports stressing the importance of CMV adrenalitis as a possible cause of adrenocortical insufficiency, we now find tuberculosis the more likely cause of total cortical destruction.

Duodenal histology in patients with celiac disease after treatment with a gluten-free diet.

BACKGROUND: The diagnosis of celiac disease requires characteristic histopathologic changes in an intestinal biopsy with clinical improvement in response to a gluten-free diet. Endoscopy with procurement of biopsy specimens is often performed to document response to the diet, but there are little data on the appearance of treated celiac disease. This study examined the endoscopic and histopathologic appearance of the duodenum of patients with celiac disease whose diet was gluten-free. METHODS: A cohort of 39 adult patients (mean age 52 years, range 20-74 years) with biopsy-proven celiac disease was retrospectively reviewed. All had responded clinically to a gluten-free diet that they had maintained for a mean of 8.5 years (range 1-45 years). The endoscopic and histopathologic appearances of the duodenal mucosa were reviewed. Blinded review of the diagnostic (initial) and post-treatment biopsy specimens was also performed to assess response of individual patients to the diet. RESULTS: The endoscopic appearance was normal in 23%, reduced duodenal folds were present in 46%, scalloping of folds in 33%, mucosal fissures in 44%, and nodularity in 33%. There was more than 1 abnormality present in 46%. Histology was normal in only 21%. The remainder had villous atrophy (69% partial, 10% total). Paired (diagnostic and follow-up) biopsy specimens were reviewed blindly for 12 patients. The mean (SD) intraepithelial lymphocyte count fell from 61 (22) to 38 (17) (normal <30 per 100 epithelial cells) and the crypt-to-villous ratio improved although it did not normalize. CONCLUSIONS: Despite a good clinical response, abnormal endoscopic and histopathologic appearances persist in the majority of patients with celiac disease treated with a gluten-free diet.

Seronegative celiac disease: increased prevalence with lesser degrees of villous atrophy.

Our aim was to assess differences in the sensitivities of serologic tests used for the diagnosis of celiac disease among patients with varying degrees of villous atrophy. Among 115 adults with biopsy-proven celiac disease who fulfilled strict criteria, including serologic testing at the time of diagnosis and response to a gluten-free diet, 71% had total villous atrophy and 29% partial villous atrophy. Endomysial antibody was positive in 77% of those with total villous atrophy, compared to 33% with partial villous atrophy (P < 0.001). There was no difference in sensitivity when the type of presentation (classical vs. silent) was compared. Endomysial antibody-positive and negative patients did not differ with respect to age at diagnosis, duration of symptoms, mode of presentation, or family history of celiac disease. All anti-tissue transglutaminase-positive patients had TVA on biopsy. Seronegative celiac disease occurs. Endomysial antibody positivity correlates with more severe villous atrophy and not mode of presentation of celiac disease. Serologic tests, in clinical practice, lack the sensitivity reported in the literature.

EUS-guided trucut needle biopsies in patients with solid pancreatic masses: a prospective study.

BACKGROUND: A trucut needle biopsy device that can be used to obtain specimens from the pancreas and other perigastric organs under EUS guidance has been developed and successfully tested in animals. Moreover, EUS-guided trucut needle biopsy has been used safely in humans and appears to provide more accurate results than EUS-guided FNA. This study prospectively assessed the clinical utility of this new device in patients with solid pancreatic masses. METHODS: Twenty-three consecutive patients with radiologically detected solid pancreatic masses underwent EUS-guided trucut needle biopsy. Pancreatic malignancy detected by EUS-guided trucut needle biopsy was considered a definitive diagnosis. Further diagnostic procedures and clinical course were used to establish or exclude the presence of malignancy in all other patients. RESULTS: Pancreatic tissue was obtained in 17 of the 23 patients (74%), including all patients in whom the transgastric approach was used. No acute or long-term complication was observed. Histopathologic evaluation revealed pancreatic cancer in 12 patients. CT-guided biopsy specimens were obtained in 4 of the 5 patients with a negative EUS-guided trucut needle biopsy result; two were positive for adenocarcinoma. Overall diagnostic accuracy was 61%. Subgroup analysis of the 16 patients in whom EUS-guided trucut needle biopsy was successful and who were available for follow-up revealed a diagnostic accuracy of 87.5%. CONCLUSIONS: This prospective study demonstrates that EUS-guided trucut needle biopsy, when performed transgastrically, is safe and accurate in the evaluation of patients with solid pancreatic masses.

Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts.

BACKGROUND & AIMS: Celiac disease is a polygenic disorder associated with HLA-DQ2 or HLA-DQ8, which are present in greater than 90% of patients. The disease is considered milder in the United States compared with Europe. We assessed whether differences in the frequency of HLA type may account for differences in severity of the disease by using cohorts of patients from New York and Paris. METHODS: HLA-DQ typing was performed on patients with celiac disease in New York and Paris. Clinical and pathologic data were compared between the New York and Parisian cohorts and also correlated with the different HLA types (HLA-DQ2, HLA-DQ2/-DQ8, HLA-DQ8). RESULTS: Among these patients, the disease was milder in the New York cohort compared with the Parisian cohort. There were fewer patients with a classical presentation (45% and 89%, respectively; P < 0.001) and less severe pathology (total villous atrophy, 64% and 89%, respectively; P < 0.05), and less marked intraepithelial lymphocytosis (intraepithelial leukocytes [IELs]/100 enterocytes, 48.1 and 82.5, respectively; P < 0.0001). HLA-DQ2 homozygotes were less prevalent in the New York cohort compared with the Parisian cohort (59% and 79%, respectively; P = 0.08). HLA-DQ8 alleles were more prevalent in the New York cohort compared with the Parisian cohort (41% and 21%, respectively; P = 0.026). There was, however, no difference in the clinical or pathologic parameters of severity when we compared the groups based on HLA type. CONCLUSIONS: HLA-DQ8 alleles were increased in the New York cohort of patients with celiac disease; however, this did not account for less severe manifestations of the disease.

Population attributable risks of esophageal and gastric cancers.

BACKGROUND: Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population-based case-control study. METHODS: We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation. RESULTS: Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%). CONCLUSION: In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.