Background: In eosinophilic esophagitis (EE), the esophagus is infiltrated with activated eosinophils that often evoke tissue damage, but the intestines of these patients remain unaffected. We thus hypothesized that different tissue-dwelling eosinophil populations may coexist: activated eosinophils that infiltrate the esophagus and resting eosinophils that reside in unaffected intestines. We sought to characterize different eosinophil subpopulations by comparing the expression of certain proinflammatory proteins in tissue-dwelling eosinophils at different parts of the gastrointestinal tract.Methods: The 8 patients participating included 6 men and 2 women with a previously confirmed diagnosis of EE, whose average age was 39.4 years (range, 20-55 yr) and average disease duration was 13.6 years (range, 2-26 yr). Controls were 3 men and I woman, with a mean age of 43.3 years (range, 29-56 yr) with untreated functional dyspepsia who underwent diagnostic esophagogastroduodenoscopy. Six additional individuals having normal blood eosinophils were recruited for cytokine measurements in blood eosinophils. Immunofluorescence and immuroassays charted expression of CD25 and the T(H)2 cytokines, interleukin (IL)-4, IL-5, IL-10, and IL-13, in esophageal, intestinal, and blood eosinophils from controls and patients.Results: Controls showed a small but significant proportion of intestinal, but no blood, cosinophils expressing CD25 and IL-13, suggesting physiologic activation occurring in the digestive tract. On the other hand, eosinophils infiltrating the inflamed esophageal mucosa of patients with EE showed strong evidence of activation, with most expressing CD25, IL-4, and IL-13. Moreover, IL-13-positive intestinal cosinophils were increased in patients compared with controls.Conclusions: We thus conclude that tissue-dwelling eosinophils show different and distinct cytokine expression patterns under noninflammatory and inflammatory conditions.

RATIONALE: Under healthy conditions, the digestive tract is the only non-hematopoietic organ showing resident eosinophils. Under inflammatory conditions, eosinophilic infiltration occurs in several organs, often leading to tissue damage. Neither the function of resting intestinal eosinophils nor the immunopathogenic mechanisms that drive resting cells to activation is clearly understood. In eosinophilic esophagitis (EE), we hypothesized that the eosinophils infiltrating the esophagus are activated and that the eosinophil population present in the intestine is resting. METHODS: To clarify the mechanisms of eosinophil activation, in healthy individuals and in EE-patients, potential activation markers (CD25, IL-4, IL-5, IL-10 and IL-13) were determined using immunofluorescence and confocal microscopy. Tissue specimens from the esophagus and the intestine and blood samples of healthy controls and EE patients were analyzed. RESULTS: In contrast to blood eosinophils which don't express these two markers, under healthy conditons 42% of intestinal eosinophils express IL-13 and 31% CD25 respectively. With EE patients, 66% of the intestinal eosinophils express IL-13 and approximately 60% of eosinophils infiltrating the inflamed esophageal mucosa express IL-13 and IL-4. CONCLUSIONS: Our data indicate heterogeneity among mucosal eosinophils. Furthermore, we suggest the following three patterns of activation of intestinal eosinophils: 1) Baseline Activation seen in the intestinal mucosa of healthy subjects, indicating that eosinophils may be actively involved in the mucosal immuno-homoestasis; 2) Primary Activation observed at the inflammation site, reflecting the eosinophils' pivotal involvement in the inflammatory process; and 3) Remote Activation noted far from the inflammatory process, consistent with a systemic activation.

Background/Aims: The presenting symptom of eosinophilic esophagitis, a chronic TH2-type inflammatory disease, is uniform dysphagia attacks. Histology reveals a dense mucosal infiltration with eosinophils. Unfortunately, endoscopic findings are often unremarkable or misleading. This study characterizes the endoscopic manifestations of eosinophilic esophagitis and analyzes the nature and clinical features of the frequently observed white alterations. Methods: Thirty adult patients (22 males, 8 females; mean age 40.6 years) with previously confirmed EE prospectively underwent a structured interview, physical examination, laboratory tests and upper endoscopy with histomorphometric examination of the esophageal mucosa. Results: On endoscopy, all patients showed mucosal abnormalities in the esophagus. Findings included an unspectacular loss of vascular pattern (93.3%) and white exudates (53.3%). Biopsies demonstrated significantly increased eosinophilia in the white exudates (108.4 vs. 14.0 cells/hpf). A significant correlation was found between white exudates and dysphagia frequency (<1 attack/week = 20%; >1 attack/ week = 70%). Conclusion: Eosinophilic esophagitis evokes at least 12 different signs resulting in an individually unique endoscopic pattern, but no disease-specific picture. White exudates correspond to foci of dense eosinophilic infiltration reflecting inflammatory activity and are associated with significantly more frequent dysphagia attacks. Both the lack of a typical endoscopic picture as well as the heterogeneity of the eosinophilic infiltration impede diagnosis.

pain episodes.For each pain episode we calculated esophageal shortening as the difference in length between emitter and receiver during 2rain before to 30 sec after pain and the 2.5min preceding period.Acid reflux and/or high amplitude or simultaneous contractions were checked dunng the same periods Results: Recordings were technically satisfactory (> 15hs) in 6 patients.Esophageal shortening could not be measured in 2 patients due to early loss of the emitter mucosal clip.One patient was asymptomatic dunng the study.We analysed 46 pain events in 5 patients (1-16/pat).In 4 patients, 16 pain events (f-7/pat) were associated with a prolonged oral LES excursion of 7.8 • 06 ram.Esophageal shortening started 70-+ 10 sec before the pain events and lasted 124-+26sec.Acid reflux was present in 5 and abnormal manometry in 10 pain events associated with esophageal shortening.Conclusion: Continuous ambulatory monitoring of esophageal shortening in man is possible.Ongoing studies will provide further information about the possible association between esophageal symptoms and abnormal contraction of the esophageal longitudinal muscle leading to prolonged esophageal shortening.

Primary eosinophilic esophagitis (PEE) is a chronic inflammatory disorder of the esophagus of unknown origin, clinically characterized by acute and recurrent dysphagia, often leading to food impaction. The established cornerstone of diagnosis is a dense infiltration of the esophagus with eosinophils. Additionally, increased T-cell and mast cell numbers are found within the epithelium of these patients. In contrast, the numbers of inflammatory cells are not increased in stomach and duodenum of PEE patients, suggesting a specific inflammatory process within the esophagus. Moreover, increased expression of interleukin-5 and turnout necrosis factor-alpha, but not eotaxin, are observed in esophageal epithelial biopsies. Despite its macro- and micro- morphological restriction to the esophagus, the inflammatory process evokes systemic effects, since peripheral blood eosinophils of PEE patients express functional IL-13, and many of these patients have increased numbers of blood eosinophils. This might be due to a stimulation of the bone marrow by the ongoing inflammatory process in the esophagus. All these clinical and immunological abnormalities are well-known in patients with asthma. These striking parallels lead to the speculation that similar mechanisms may account for the inflammatory Process in asthma, as well as in PEE.

Background: Primary eosinophilic esophagitis, a chronic inflammatory disorder of the esophagus, evokes recurrent dysphagia. Endoscopy is often unremarkable, and no consensus exists regarding management of resultant dysphagia. The response of a series of patients with primary eosinophilic esophagitis to dilation is reported together with a description of a possibly pathognomonic sign: fragile esophageal mucosa, for which the term “crêpe-paper” mucosa is introduced. Methods: Five men underwent endoscopy because of dysphagia confirmed (clinically, endoscopically, and histologically) to be caused by primary eosinophilic esophagitis and were treated by bouginage. Observations: All patients had extremely fragile, inelastic, and delicate mucosa, which tore easily even with minor trauma. After the procedure, patients remained asymptomatic for 3 to 24 months. Conclusions: Primary eosinophilic esophagitis is characterized by fragile esophageal mucosa that readily tears in response to minor trauma during otherwise uneventful diagnostic endoscopy. This “crêpe-paper” sign may alert endoscopists to the presence of the disease when other mucosal alterations are lacking. Dilation is effective for patients with symptoms with minimal morbidity, despite development of disquieting lesions in response to the procedure.

BACKGROUND & AIMS Primary eosinophilic esophagitis is a chronic, increasingly recognized, interleukin 5-driven inflammatory disorder of the esophagus. The leading symptom in adults is uniform attacks of dysphagia, and the established histologic sign is a dense eosinophilic infiltration of the esophageal epithelium. Before this study, the natural course of eosinophilic esophagitis had not been defined and information regarding potential long-term risks was lacking. METHODS This prospective case series included 30 adult patients with eosinophilic esophagitis (22 men and 8 women; mean age, 40.6 years) whose diagnosis had been made >1 year before study debut based on typical history, consistent endoscopic abnormalities, and infiltration of the esophageal epithelium with >24 eosinophils/high-power field. After a mean of 7.2 years, patients underwent a comprehensive follow-up examination. RESULTS All patients survived the study period in good health and stable nutritional state. Dysphagia persisted in 29 patients, exerting a major negative effect on socioprofessional activities on 1 patient and a minor impact on 15. Attacks of dysphagia were more frequent in patients with blood eosinophilia or pronounced endoscopic alterations. The esophageal eosinophilic infiltration persisted in all symptomatic patients, but cell numbers spontaneously decreased significantly (78.7 vs. 40.3 cells/high-power field). The inflammatory process evoked fibrosis of the esophageal lamina propria but did not spread to the stomach or duodenum. No case evolved to a hypereosinophilic syndrome. CONCLUSIONS Eosinophilic esophagitis, a primary and chronic disease restricted to the esophagus, leads to persistent dysphagia and structural esophageal alterations but does not impact the nutritional state. To date, no malignant potential has been associated with this disease.

We present two cases initially diagnosed as Crohn's disease which were treated with immunosuppressive drugs. In both patients the development of an amoebic liver abscess led to the correct diagnosis of amoebic dysentery. The pitfalls of the diagnosis of amoebic colitis and the possible influence of immunosuppression in the development of extraintestinal amoebiasis are discussed.

Bowen's disease of the anal region is a rare, slow-growing, intraepidermal squamous-cell carcinoma (carcinoma in situ). If surgical excision is incomplete, there is a risk of subsequent development of malignancy and metastasis. Between 1980 and 1995 we treated 11 patients (8 female, 3 male) with anal Bowen's disease. The mean age was 55 (34-75) years. The main reason for excision was: pain (4), itching (3), bleeding (3) and a disturbing lump (3). The intraoperative findings were in all cases a lesion at the anocutaneous line: perianal or intra-anal tumor (6), erosion (2) or ulceration (2) as well as lichenoid lesion (4) or hyperpigmentation (3). The procedure was excision of the lesion in 10 cases. Only in one case was a biopsy taken. 3 patients had to be operated on a second time for reasons of radicality. 5 years after primary diagnosis, one patient developed a recurrent invasive squamous-cell carcinoma and had to undergo perineo-abdominal rectum amputation with postoperative radiotherapy (2 years after operation). Only one patient underwent a biopsy, which produced the diagnosis of invasive squamous-cell carcinoma. He underwent combined chemo-radiotherapy. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic. The recommended therapy is complete surgical excision. With complete excision no recurrences do occur.

In 10 patients presenting with acute recurrent dysphagia, seen over a 4-year period, idiopathic, eosinophilic esophagitis (IEE) was diagnosed. The diagnosis was confirmed histologically. Dysphagia of other causes or other diseases causing eosinophilic infiltration was ruled out. Endoscopy showed discrete white structures in the esophagus which were partly finely reticular or plaque-like in 9 of the 10 patients. Of these one had a web and another a mucosal ring. Peripheral eosinophilia and elevated IgE-levels were found in 70% of the cases. To date IEE has been thought to be a rare disorder. Emerging evidence suggests its prevalence has been underestimated. It may also be the most frequent form of eosinophilic gastroenteropathy. The flat, only endoscopically visible form may be more common than the proliferative type. With knowledge of the typical history and of the distinct endoscopic pattern, and with adequate diagnostic workup, the disease will be found more often in the future. Prompt diagnosis also avoids further diagnostic procedures and permits rapid remission through treatment with steroids and antihistamines.

The results of surgical resection in early gastric cancer were analyzed retrospectively. These operations were performed between 1982 and 1991 on 52 consecutive patients (29 women, 23 men; average age 64 [35-85] years). The tumours were resected by total gastrectomy in 11, by subtotal gastrectomy in 31, and by Billroth I resection in 10, followed by limited lymphadenectomy of the perigastric group of lymph-nodes (D1 dissection). There was one operative death (1.9%). The tumor was confined to the mucosa in 36 patients (69%), while submucosal infiltration was present in 16 (31%) and metastases to the regional lymph-nodes in seven (13%). Follow-up examination took place in all patients, after an average period of observation of 6.1 years. For the total group the 5-year survival rate, including operative mortality, was 83.7%. It correlated with the depth of penetration of the tumour and nodal involvement. 5-year survival rate for mucosal tumour was 90%, with submucosal infiltration 66.7% (P < 0.03), without lymph-node metastasis 86.4%, with it 68.6% (P < 0.05). The extent of resection and the tumour classification (according to Laurén--intestinal or diffuse) did not influence survival.--Early gastric cancer, contrary to that in the advanced stages, has a very good prognosis. But it is significantly altered by the depth of penetration of the tumour and nodal metastasis.

The results of surgical resection in early gastric cancer were analysed retrospectively. These operations were performed between 1982 and 1991 on 52 consecutive patients (29 women, 23 men; average age 64 [35-85] years). The tumours were resected by total gastrectomy in 11, by subtotal gastrectomy in 31, and by Billroth I resection in 10, followed by limited lymphadenectomy of the perigastric group of lymph-nodes (D-1 dissection). There was one operative death (1.9%). The tumour was confined to the mucosa in 36 patients (69%), while submucosal infiltration was present in 16 (31%) and metastases to the regional lymph-nodes in seven (13%). Follow-up examination took place in all patients, after an average period of observation of 6.1 years. For the total group the 5-year survival rate, including operative mortality, was 83.7%. It correlated with the depth of penetration of the tumour and nodal involvement. 5-year survival rate for mucosal tumour was 90%, with submucosal infiltration 66.7% (P < 0.03), without lymph-node metastasis 86.4%, with it 68.6% (P < 0.05). The extent of resection and the tumour classification (according to Lauren intestinal or diffuse) did not influence survival. Early gastric cancer, contrary to that in the advanced stages, has a very good prognosis. But it is significantly altered by the depth of penetration of the tumour and nodal metastasis.

As the modern treatment for anal carcinoma is either radiotherapy alone or combined radiochemotherapy, an exact histological staging is impossible. Therefore we have to depend on an accurate preoperative staging method. Endoanal ultrasonography enables imaging of the normal anal canal and its pathologies.

We observed the rare case of a 50-year-old man with intestinal obstruction due to an inflammatory fibroid polyp (IFP) of the jejunum. Here, we report its clinical and pathological characteristics, and its histologic appearance. Limited small bowel resection led to complete recovery of the patient. In a short review of the literature, possible pathogenetic mechanisms as well as diagnostic and therapeutic means are discussed. Although rare, IFP should be considered in the differential diagnosis of small bowel obstruction.

Endorectal ultrasound is the most reliable method in staging rectal cancer and is superior to computed tomography. In a prospective series of 152 consecutive patients, comparison of preoperative ultrasound staging and postoperative histopathological staging resulted in an overall accuracy of 90.1%. Overstaging was observed in 9.2%, understaging in 0.7%. Peritumoral inflammatory changes, preoperative radiotherapy and localization of the tumor in the lower rectum were the main reasons for overstaging. Understaging was seen in stenotic or only minimal invasive tumors. Accuracy in staging lymph nodes was 78.5%. Inflammatory changes in the nodes were responsible for either overstaging or understaging. Whether diagnosis will be improved with a higher frequency-mainly in lymph nodes - has yet to be proved. With knowledge of the reasons for misinterpretation, endorectal sonography is mainly in the lower rectum - a valuable aid in evaluation of surgical procedure.

Endorectal ultrasound is the most reliable method in staging rectal cancer and is superior to computed tomography. In a prospective series of 152 consecutive patients, comparison of preoperative ultrasound staging and postoperative histopathological staging resulted in an overall accuracy of 90.1%. Overstaging was observed in 9.2%, understaging in 0.7%. Peritumoral inflammatory changes, preoperative radiotherapy and localization of the tumor in the lower rectum were the main reasons for overstaging. Understaging was seen in stenotic or only minimal invasive tumors. Accuracy in staging lymph nodes was 78.5%. Inflammatory changes in the nodes were responsible for either overstaging or understaging. Whether diagnosis will be improved with a higher frequency--mainly in lymph nodes--has yet to be proved. With knowledge of the reasons for misinterpretation, endorectal sonography is--mainly in the lower rectum--a valuable aid in evaluation of surgical procedure.

The endoluminal sonography is a new investigation in staging rectal cancer. In a prospective series the value of the endoluminal sonography is compared with clinical staging and computed tomography. The accuracy in clinical staging, computed tomography and endoluminal sonography was 77%, 76% and 87%, respectively. The reasons for under- and overstaging and the interpretation of perirectal lymphnodes are discussed. The endoluminal sonography is an important new method evaluating the operative procedure of cancers in the lower rectum.

Cirrhosis of the liver was diagnosed in an 18-year-old man with histiocytosis X. Electron microscopy and immunohistochemistry revealed infiltration of the liver by the typical cellular elements of histiocytosis X. Endoscopic retrograde cholangiography showed alterations resembling those of sclerosing cholangitis. Sixteen months later, the patient died of recurrent variceal bleeding and cholangiosepsis. Autopsy confirmed that cirrhosis was the main manifestations of the underlying disease. Thus, cirrhosis of liver can be a main and potentially fatal manifestation of histiocytosis X beyond the pediatric age range. Histiocytosis X may lead to parenchymal infiltration of the liver and to changes of the major bile ducts resembling sclerosing cholangitis. The diagnosis of hepatic histiocytosis X can easily be missed without relying on appropriate electron microscopic and immunohistochemical investigations.