Manfred Stolte

Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease

Previous studies on the frequency of intestinal mast cells and eosinophils in patients with inflammatory bowel disease yielded conflicting results. In the present morphometric study, we quantified mast cells and eosinophils in the lamina propria by histological and immunohistochemical methods in 64 patients suffering from Crohn’s disease (33 cases) or ulcerative colitis (31 cases), and in 29 controls. Histological data from 206 biopsies were related to the presence of mucosal inflammation and clinical parameters. The number of eosinophils was increased in patients with inflammatory bowel conditions (meanu2003±u2003SE: 331u2003±u200344/mm2) as compared to controls (258u2003±u200327/mm2), and was dependent on disease activity and drug treatment. Mean mast cell numbers did not differ between patients and controls. However, a reduced mast cell number was found in toluidine blue‐stained sections of actively inflamed tissue areas (143u2003±u200316/mm2, versus 206u2003±u200318/mm2 in non‐inflamed tissue). Immunohistochemical studies using antibodies against the granule proteins tryptase and chymase suggest that this decrease in mast cell numbers is due to mast cell degranulation. The present data show that the number of intestinal mast cells and eosinophils is altered in patients with inflammatory bowel diseases, suggesting that both cell types are involved in the pathogenesis of chronic intestinal inflammation.

KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett's esophagus

BACKGROUNDnThe rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barretts esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barretts esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barretts esophagus.nnnMETHODSnEight men and 2 women 43 to 84 years of age with short segments of Barretts esophagus or traditional Barretts esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barretts mucosa.nnnRESULTSnTwo to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months).nnnCONCLUSIONSnKTP laser destruction of Barretts esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barretts esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barretts esophagus seems to be feasible and safe in short segments of Barretts esophagus with dysplasia or early cancer.

Differences in the diagnostic criteria used by japanese and western pathologists to diagnose colorectal carcinoma

In view of the many studies of early stage colorectal carcinoma from Japan, it is essential to know whether the criteria for the histologic diagnosis of colorectal carcinoma are similar in Japan and Western countries.

Solid and cystic pancreatic tumors. Clinical, histochemical, and electron microscopic features in ten cases.

Ten cases of the rare solid and cystic pancreatic tumors are presented. All except one occurred in young women (mean age, 25 ± 9.2 years). The large neoplasms were evenly distributed across the pancreas; in one case, metastasis occurred; all other cases were free from disease after complete resection. Histologic hallmarks of solid and cystic neoplasms were papillary growth, large intracytoplasmic granules, and immunoreactivity with α1‐antitrypsin, α1‐antichymotrypsin, phospholipase A2, and neuroendocrine markers (neuron‐specific enolase [NSE], synaptophysin). This suggests both endocrine as well as exocrine differentiation.

Differences in diagnostic criteria for esophageal squamous cell carcinoma between Japanese and Western pathologists.

Large discrepancies have been found between Western and Japanese pathologists in the diagnosis of adenoma/dysplasia versus carcinoma for gastric and colorectal glandular lesions. It is important to determine whether similar differences exist in the diagnosis of esophageal squamous lesions.

Endoscopic Resection of Superficial Esophageal Squamous-Cell Carcinomas: Western Experience

OBJECTIVES:Endoscopic resection of esophageal squamous-cell neoplasia with curative intent appears to be an alternative treatment to radical surgery when the malignant neoplasia is intraepithelial or limited to the mucosal layer, since the risk for lymph-node metastases is very low. In contrast to Japan, there has so far been only limited experience in Europe and the United States with endoscopic resection in such cases. In the present observational study, we report on the largest prospective series so far in Western countries of patients with early squamous-cell cancer or carcinoma in situ, who were treated using endoscopic resection therapy.METHODS:Between December 1997 and November 2001, 115 patients with a suspicion of early squamous cancer were referred for local endoscopic therapy. A total of 39 patients (mean age 61.4 ± 10.2 yr) with early esophageal carcinoma (n = 29) and carcinoma in situ (Cis) (n = 10) fulfilled the criteria for local endoscopic therapy and were treated using endoscopic resection. Ten patients had Cis (group A), 19 had mucosal cancer (group B), and 10 had submucosal cancer (group C). All patients in group C were inoperable or had refused surgery.RESULTS:A total of 94 resections were performed. Nine of the 10 patients in group A (90%), 19 of the 19 in group B (100%), and 8 of the 10 in group C (80%) achieved a complete response during a mean follow-up period of 29.7 ± 14.3 months. Tumor-related deaths occurred in three patients (one in group B, who was inoperable; two in group C, who refused surgery). No major complications such as perforation or bleeding requiring blood transfusion occurred. Minor complications were seen in six patients (15%)—three with minor bleeding after endoscopic resection and three with esophageal stenoses, who were successfully treated using injection therapy or dilatation. Calculated 5-yr survival was 90% in group A, 89% in group B, and 0% in group C.CONCLUSIONS:Endoscopic resection appears to be an effective and safe method of curative treatment in patients with Cis and mucosal squamous-cell carcinomas of the esophagus. The preferred method in patients with submucosal cancer should be esophagectomy or chemoradiotherapy, whenever possible.

Immunohistological assessment of intestinal eosinophil activation in patients with eosinophilic gastroenteritis and inflammatory bowel disease

OBJECTIVE:To assess the activation grade of intestinal eosinophils in patients with eosinophilic gastroenteritis (EOG), ulcerative colitis (UC), Crohns disease (CD), and controls by immunohistochemistry.METHODS:Cecal biopsies were collected from healthy controls and from patients with EOG, CD, UC, and other noninflammatory GI diseases. Immunohistochemistry was performed in sequential sections stained with monoclonal antibodies directed against eosinophil cationic protein (ECP) or eosinophil protein X (EPX) stored in eosinophil granules (EG1) and that secreted by activated eosinophils (EG2). The ratio of EG1 to EG2-positive eosinophils expressed as percentage of lamina propria cells was calculated. ECP and EPX were measured in serum and feces.RESULTS:The percentage of EG1 and EG2-positive lamina propria cells was elevated in EOG and slightly, but not significantly, in UC. The ratio of EG1 to EG2-positive cells was decreased in CD, UC, and other patients as compared to healthy controls. Particularly low EG1 to EG2 ratios were found in EOG. Correspondingly, fecal and serum levels of ECP and EPX, respectively, were highest in patients with EOG. The EG1 to EG2 ratio was negatively correlated with fecal ECP and EPX levels. At sites of actively inflamed mucosa, the EG1 to EG2 ratio was lower than in noninflamed tissue.CONCLUSIONS:Our data strongly suggest that the EG1 to EG2 ratio may be a marker of tissue eosinophil activation. Low ratios (<1) indicate eosinophil activation, whereas ratios ≥1 are found in healthy controls. Furthermore, we show that EOG is characterized by a pronounced intestinal eosinophil accumulation and activation, whereas in CD and UC, eosinophils seem to be activated but their number is not or only slightly elevated compared to controls.

Somatostatinoma of Vater's papilla and of the minor papilla.

Two cases of somatostatinomas of the major and minor papilla are reported. The tumors were characterized by solid trabecular and tubular arrangements of tumor cells and in one case by the presence of microvilli and psammoma bodies. The tumor cells contain many amine precursor uptake and dicarboxylation (APUD)‐granules with a diameter of 300 to 500 nm and low electron density. Immunoperoxidase stain showed intense staining only for somatostatin and low density of neuron‐specific enolase. Those tumors either resulted from pluripotent endocrine cells or from D‐cells of the mucosa or glands of the papilla.

Distinction of High-Grade Intraepithelial Neoplasia and Tubular Gastric Adenocarcinoma

In 2000, the World Health Organization (WHO) recommended to no longer use the term “dysplasia” but rather “intraepithelial neoplasia” throughout the gastrointestinal tract. This change has been suggested because the term dysplasia has been overstressed in the past (Table 1) because of the weak descriptive nature of its definitions. Also, the term dysplasia was used in part for early carcinomas [4]. The WHO classification [5] describes high-grade intraepithelial neoplasia in the stomach as a lesion with “glandular crowding and prominent cellular atypia. Tubules can be irregular in shape, with frequent branching and folding: there is no stromal invasion.” Mucin secretion is believed to be absent or minimized. Additionally, increased proliferative activity is present throughout the epithelium. According to the WHO classification, invasive adenocarcinoma is diagnosed whenever the tumor invades into the lamina propria or the submucosal layer. Also mentioned is that in bioptic diagnosis isolated tumor cells and glandlike and/or papillary projections are believed to help differentiate it from intraepithelial neoplasia.

Early Neoplasia in Barrett’s Esophagus

Over the last 10–20 years, the incidence of adenocarcinomas in Barrett’s esophagus has increased enormously in many Western countries [1]–[5]. The increase in these countries is greater than that of all other malignant epithelial tumors, so that the term “new epidemic” has even been applied [6].