Isolated visceral manifestation of Buerger's disease presenting as intestinal obstruction: a case report.

Introduction and importance: Buerger's disease is an uncommon segmental nonatherosclerotic vasculitis essentially affecting small to medium-sized arteries and veins of upper and lower extremities and can lead to limb amputation. Visceral vessel involvement is quite rare accounting for 2% of cases presenting with acute abdomen due to mesenteric ischemia. Moreover, isolated visceral involvement is even rare. Case presentation: A 42-year-old gentleman, a chronic smoker, presented with abdominal pain associated with nausea and vomiting and loose stool of 2 months duration. Magnetic resonance enterography revealed segmental circumferential wall thickening with stricture in the mid part of the jejunum with lymphadenopathy features of possible inflammatory bowel disease (Crohn's disease). Furthermore, intraoperative surgical findings were also suggestive of Crohn's disease. However, histologic findings were consistent with thromboangiitis obliterans. Discussion: Thromboangiitis obliterans can present with inflammatory vascular lesions without necrosis in the early stage to varying degrees of recanalisation, gangrene, and amputation in the late stage. It rarely involves the brain, heart, and abdominal viscera. The visceral involvement may be in the form of intestinal obstruction or mesenteric ischemia or can mimic Crohn's in a background of smoking. Conclusion: This case report will help to learn more about the rarer intestinal presentation of intestinal Buerger's disease. It can present with features of bowel ischemia, obstruction or Crohn's. So, histology would play a pivotal role in differentiating the diagnostic dilemma.

Sporadic Fundic Gland Polyps With Low-Grade Dysplasia: A Large Case Series Evaluating Pathologic and Immunohistochemical Findings and Clinical Behavior.

OBJECTIVES: Fundic gland polyps (FGPs) occur in two clinical settings, sporadic and syndromic. Epithelial dysplasia is rare in sporadic FGPs, and progression data from large series are lacking. The aim of this study was to evaluate the clinical, morphologic, and immunohistochemical features in a large series of sporadic FGPs with epithelial dysplasia. METHODS: We studied 85 patients with FGPs with low-grade dysplasia (FGPD), including 62 patients with sporadic and 23 with syndromic FGPDs. RESULTS: Sixty-two patients with sporadic FGPD comprised 29 men and 33 women with a median age of 56 years. The indications for endoscopy were heartburn and follow-up of Barrett esophagus, and 49 patients had a history of proton pump inhibitor use. Morphologically, sporadic and syndromic FGPDs were similar. Immunohistochemical staining for p53 was normal (weak 1+) in all polyps, Ki-67 immunohistochemistry showed staining in the mucus neck and surface epithelium, and nuclear accumulation of ß-catenin was observed in 9 of 40 sporadic FGPDs. Twenty-six (42%) patients with sporadic FGPDs had follow-up esophagogastroduodenoscopies with biopsies after a mean period of 14.8 months (nine with more than one follow-up): nine (35%) had no additional polyps, 13 (50%) had nondysplastic sporadic FGPs, and four (15%) had sporadic FGPDs. CONCLUSIONS: Sporadic FGPDs were seen primarily in middle-aged patients with gastroesophageal reflux. Follow-up data support the indolent nature of these polyps.

Retained capsule endoscope leading to the identification of small bowel adenocarcinoma in a patient with undiagnosed Crohn disease.

Small intestinal neoplasia is a rare condition that frequently presents a diagnostic challenge. We describe the case of a 70-year-old patient who presented with several years of chronic, intermittent abdominal pain, previously diagnosed as irritable bowel syndrome. Radiographic evaluation, including upper gastrointestinal series with small bowel follow-through and computed tomography, demonstrated dilated small bowel with possible strictures. Colonoscopy and upper endoscopy were unrevealing. Attempted capsule endoscopy resulted in capsule retention. Subsequent laparoscopy led to the identification of severe, active Crohn disease with strictures, ulcers, crypt abscesses, pyloric metaplasia, and transmural inflammation. Extensive flat and polypoid high- and low-grade dysplasia were present, as well as an area of well-differentiated adenocarcinoma invading into the muscularis propria. We discuss the epidemiology, pathogenesis, and diagnosis of small bowel malignancy.

Hepatic adenomatosis.

Hepatic adenomatosis was first described in 1985 by Flejou et al as multiple adenomas, arbitrarily more than 10, in an otherwise normal liver parenchyma. Several authors have suggested that it is a distinct entity from hepatic adenoma, which is predominantly seen in young women taking oral contraceptives. Although considered a benign disease, it can be associated with potentially fatal complications such as malignant transformation and intraperitoneal hemorrhage due to rupture. Although its etiology and natural history have not been fully elucidated, germline mutation of hepatocyte nuclear factor 1alpha, which is associated with maturity-onset diabetes of the young type 3, has recently been implicated in a subset of cases. Currently, there is no consensus on patient management. However, surgical removal of large lesions may significantly improve symptoms and reduce the risk of complications. Genetic counseling may now play an important role in case management.

Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease.

Differentiating eosinophilic esophagitis from gastroesophageal reflux disease is important given their pathogenetic differences and responses to therapy. Eotaxins are a family of chemokines important for activation and recruitment of eosinophils mediated by their receptor, chemokine receptor-3 (CCR-3). Interleukin 5 (IL-5) is a key cytokine involved in many steps of eosinophil production and recruitment. The aim of this study was to compare the messenger RNA expression of the eotaxins, CCR-3, and IL-5 between well-characterized groups of patients with eosinophilic esophagitis, patients with gastroesophageal reflux disease, and healthy individuals. This was a retrospective study using esophageal biopsies from 33 patients with eosinophilic esophagitis, 20 patients with gastroesophageal reflux disease, and 17 healthy controls. Parameters studied included demographic features, presenting symptoms, endoscopic findings, histopathologic features, and messenger RNA levels of eotaxins 1, 2, and 3, CCR-3, and IL-5 by quantitative real-time polymerase chain reaction using formalin-fixed, paraffin-embedded tissue. Patients with eosinophilic esophagitis were predominantly males (M/F=3:1), with a mean age of 15.9 years and a mean eosinophil count of 55 per x400 high-power field. Patients with gastroesophageal reflux disease had a mean age of 31.5 years and a mean eosinophil count of 5.8 per high-power field. Total intraepithelial eosinophil and lymphocyte counts, the presence of superficial eosinophil clusters, microabscesses, and basal cell hyperplasia were all significantly associated with eosinophilic esophagitis as opposed to gastroesophageal reflux disease (P<.0001). The mean expression levels of eotaxin-3 were markedly elevated in patients with eosinophilic esophagitis as compared with the gastroesophageal reflux disease and healthy control groups (731+/-276, 31+/-12, and 1.5+/-0.4 pg/ng beta-actin, respectively; P<.001). Mean expression levels of eotaxins 1 and 2, IL-5, and CCR-3 were also significantly increased in the patients with eosinophilic esophagitis, albeit at lower levels than eotaxin-3. In conclusion, our results highlight the important contribution of eotaxin-3 in the pathogenesis of eosinophilic esophagitis. Determination of eotaxin-3 levels by real-time polymerase chain reaction on paraffinized, formalin-fixed tissue may be a useful test in the differentiation of eosinophilic esophagitis from gastroesophageal reflux disease.

Dedifferentiated liposarcoma arising from the sigmoid mesocolon: a case report.

Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. It occurs most commonly in the retroperitoneum and rarely in other anatomic locations. In the present report, we describe a case of dedifferentiated liposarcoma that occurred in an unusual location, sigmoid mesocolon, which has not yet been documented.

Coronary sinus and fossa ovalis ablation: effect on interatrial conduction and atrial fibrillation.

BACKGROUND: Interatrial conduction occurs via discrete pathways along the coronary sinus musculature, fossa ovalis region, and Bachman's bundle. We assessed the feasibility of altering interatrial conduction by selectively ablating two of these conduction pathways using a novel mesh electrode ablation catheter. METHODS: Circular radiofrequency energy catheter ablation lesions were created in the proximal coronary sinus in four dogs and in both the fossa ovalis and the proximal coronary sinus regions in seven pigs. Interatrial conduction was assessed by analyzing intracardiac electrogram and noncontact isopotential mapping data. Inducibility of atrial fibrillation was assessed before and after ablation (in six pigs). RESULTS: Ablation lesions in the proximal coronary sinus eliminated interatrial conduction along the coronary sinus musculature in four dogs and five of seven pigs. Ablation lesions in the fossa ovalis region eliminated interatrial conduction via midseptal pathways in six of seven pigs. Atrial fibrillation, inducible in five of seven pigs at baseline, was rendered noninducible in all five. There was no adverse effect on AV nodal conduction. CONCLUSIONS: (1) Using a novel mesh electrode ablation catheter, we were able to ablate interatrial conduction pathways along the proximal coronary sinus and fossa ovalis regions. (2) This altered interatrial conduction and altered atrial fibrillation inducibility and maintenance. (3) Catheter ablation of interatrial conduction pathways may be useful in the therapy of atrial fibrillation.

Computerized morphometry as an aid in determining the grade of dysplasia and progression to adenocarcinoma in Barrett's esophagus.

The aims of this study were to use computerized morphometry in order to differentiate between the degree of dysplasia and to predict progression to invasive adenocarcinoma in Barrett's esophagus (BE). Biopsies from 97 patients with BE graded by a consensus forum of expert gastrointestinal pathologists were available for morphometrical analysis. The study group included 36 biopsies negative for dysplasia (ND), none of which progressed to carcinoma; 16 indefinite for dysplasia (IND) and 21 low-grade dysplasia (LGD), of which three progressed in each group and 24 high-grade dysplasia (HGD), of which 15 progressed to invasive carcinoma. Computerized morphometry was used for measuring indices of size, shape, texture, symmetry and architectural distribution of the epithelial nuclei. Low-grade dysplasia was best differentiated from the ND group by nuclear pseudostratification (P=0.036), pleomorphism (P<0.01), and chromatin texture (margination, P<0.01) and from the HGD group by nuclear area (P<0.01), pleomorphism (P<0.01), chromatin texture (margination, P<0.01), symmetry (P<0.01), and orientation (P=0.027). These results were validated on a new set of cases (n=55) using a neural network model, resulting in an accuracy of 89% for differentiating between the ND and LGD groups and 86% for differentiating between the LGD and HGD groups. Within the HGD group, univariate significant predictors of the progression interval to carcinoma were: indices of nuclear texture (heterogeneity: P=0.0019, s.d.-OD: P=0.005) and orientation: P=0.022. Nuclear texture (heterogeneity) was the only independent predictor of progression (P=0.004, hazard=11.54) by Cox's multivariate test. This study proposes that computerized morphometry is a valid tool for determining the grade of dysplasia in BE. Moreover, histomorphometric quantification of nuclear texture is a powerful tool for predicting progression to invasive adenocarcinoma in patients with HGD.

Claudin expression in gastric adenocarcinomas: a tissue microarray study with prognostic correlation.

The claudins comprise a multigene family of integral membrane proteins, which play a major role in tight junction formation. Aberrations in the expression of certain claudins have been described in a number of malignancies. Our aims were to determine the expression pattern of claudins 1, 3, and 4 as well as ZO-1 in a large series of US patients with gastric cancer and to correlate expression with clinicopathologic and prognostic variables. Tissue microarrays were created from paraffinized samples from 146 patients with distal gastric adenocarcinomas (61 intestinal and 85 diffuse or mixed subtypes). In addition, cores of normal mucosa and intestinal metaplasia were taken from most cases. The microarrays were stained for claudins 1, 3, and 4 and ZO-1, and the intensity of staining was determined using a 3-point scale. Moderate claudin 1 and ZO-1 membranous staining were present, whereas only focal weak claudin 3 and 4 membranous staining was present in normal gastric epithelium. Moderate to strong staining of claudins 1, 3, 4, and ZO-1 was detected in 74%, 48%, 62%, and 74% of the intestinal but in only 46%, 24%, 45%, and 36% of the diffuse subtype of adenocarcinomas (P < .05). Cox multivariate analysis revealed that tumor stage, diffuse subtype, and moderate to strong claudin 4 staining were associated with decreased survival (P < .02). In conclusion, claudins 1, 3, and 4 and ZO-1 are strongly expressed in most gastric intestinal-type adenocarcinomas but less frequently in diffuse gastric cancers. The up-regulation of claudin expression during gastric carcinogenesis suggests their potential utility as diagnostic biomarkers and possible targets for therapeutic intervention.

Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions.

Deep fibromatoses (desmoid tumors) are clonal myofibroblastic proliferations that are prone to aggressive local recurrences but that do not metastasize. They must be distinguished from a host of fibroblastic and myofibroblastic lesions as well as from smooth muscle neoplasms. Virtually all deep fibromatoses have somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations leading to intranuclear accumulation of beta-catenin. Since low-grade sarcomas in general lack beta-catenin and since reactive proliferations would not be expected to have it, we predicted that nuclear beta-catenin expression would be detected in deep fibromatoses but absent in other entities in the differential diagnosis. We evaluated the role of beta-catenin to help differentiate distinguish deep fibromatoses from congeners. Formalin-fixed, paraffin-embedded sections from 21 lesions from 20 patients with deep fibromatoses were stained with monoclonal beta-catenin antibody (Transduction Laboratories) and compared with low-grade fibromyxoid sarcoma (n=12), leiomyosarcoma (n=10), various other fibrosarcoma variants (n=13, including 3 myofibrosarcomas, 3 sclerosing epithelioid fibrosarcomas, 5 low-grade fibrosarcomas, 1 classic fibrosarcoma arising in dermatofibrosarcoma protuberans, 1 inflammatory myxohyaline tumor/myxoinflammatory fibroblastic sarcoma), myofibroma/myofibromatosis (n=12), nodular fasciitis (n=11), and scars (n=9). Nuclear and cytoplasmic staining was assessed. All 21 examples of deep fibromatosis displayed nuclear beta-catenin (focal nuclear staining in one case to 90% staining). All other lesions tested (n=67) lacked nuclear labeling for beta-catenin, showing only cytoplasmic accumulation. beta-Catenin immunohistochemistry separates deep fibromatosis from entities in the differential diagnosis, a finding that can be exploited for diagnosis. Most fibromatoses have diffuse nuclear staining although occasional examples only focally label.

Application of adjunct techniques in cytologic material in the diagnosis of rhabdomyosarcoma: case report and review of the literature.

A 4(1/2)-yr-old female presented with right-sided pleural effusion and a retroperitoneal mass. Cytologic analysis of the pleural fluid yielded malignant small round blue cells, which were noncohesive, 3-4 times the size of lymphocytes. The malignant cells had hyperchromatic, pleomorphic nuclei with moderate amounts of vacuolated cytoplasm. A few fiber-shaped cells were also seen. Immunostains for desmin, muscle-specific actin were positive; ultrastructural findings of thick and thin actin-myosin filaments confirmed the diagnosis of embryonal rhabdomyosarcoma. This case illustrates the importance of performing appropriate immunohistochemical stains and ultrastructural studies on cytological material to arrive at a definitive diagnosis.