Immune modulation by non-hodgkin lymphoma in a patient with two primary intestinal T-cell lymphomas and long-standing celiac disease.

Tumors may influence immunologic reactions. Here, we report on a 72-year-old patient who suffered from celiac disease (CD) that had been diagnosed 20 years before. Under a normal diet but without any evidence of enteropathy or CD-associated antibodies, the patient developed a jejunal T-cell lymphoma. It was resected due to perforation and four courses of IMVP-16 were added. The patient started and kept a strict gluten-free diet (GFD). Two years later, he presented with weight loss and a clonally divergent refractory sprue type II with loss of antigen (CD8; T-cell receptor-beta) expression in intraepithelial lymphocytes. At this time point, he showed high titers of CD-associated antibodies, although he was on a strict GFD. This case report highlights several questions: the missing enteropathy under a gluten-containing diet supports the notion of immune suppression in malignant diseases, especially non-Hodgkin lymphoma. Secondly, the patient developed an early form of a second independent T-cell lymphoma (refractory sprue type II) under a strict GFD, then with CD-associated antibodies, which raises the question whether the clonal intraepithelial lymphocytes were stimulating antibody production. Thus, the single detection of CD-associated antibodies in patients with CD is not itself proof of noncompliance with GFD.

[Current diagnosis and therapy of esophageal carcinoma]. / Aktuelle Diagnostik und Therapie des Osophaguskarzinoms.

In Germany the incidence of esophageal cancer is 6 - 10 per 100,000. At the time of diagnosis about 75 % of the patients suffer from UICC stage III or IV esophageal cancer. Less than 10 % of patients are diagnosed with early (T1) cancer. Diagnosis and staging relies on esophagoscopy including biopsies, endoscopic ultrasonography, and computerized tomography of the chest and abdomen. Intramucosal early cancer (T1a) and high-grade dysplasia can be treated either by surgery or by endoscopic mucosal resection. Chemoradiation is the definitive treatment of choice for localized squamous cell cancer of the proximal esophagus. As far as overall survival is concerned definitive chemoradiation is not inferior to esophagectomy even in patients with localized squamous cell cancer of the middle or lower esophagus. In case of high surgical risk chemoradiation should be offered to those patients as the therapy of choice. Esophagectomy should be performed in operable patients suffering from resectable adenocarcinoma of the esophagus. Preoperative chemoradiation is recommended in locally advanced (non-resectable) adenocarcinoma. If staging reveals distant metastases, palliative therapy is indicated. Palliative chemotherapy with 5-fluorouracil and cisplatin should be offered to patients with good performance status. Esophageal intubation (with expandable metal stents) is the palliative treatment of choice for firm stenosing, non-resectable tumors, where rapid relief of dysphagia is required.

A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma.

BACKGROUND AND AIMS: This study assessed the efficacy and safety of irinotecan (CPT-11) in the treatment of patients with unresectable esophageal carcinoma. PATIENTS AND METHODS: Ten patients with esophageal squamous cell carcinoma (SCC) and three with adenocarcinoma (AC) were treated with CPT-11. Eight of the 13 patients were pretreated by surgery, radio-, or chemotherapy. CPT-11 was administered in repeated 6-week cycles consisting of CPT-11 once weekly for 4 weeks, followed by a 2-week rest. The starting dose of CPT-11 was 125 mg/m(2) given intravenously over 60 min; subsequent doses were adjusted based on tolerance and toxicity. Nine patients were evaluable for response. RESULTS: Two patients showed a partial response (one SCC, one AC) and two others disease stabilization (one SCC, one AC). The mean time to progression was 3.8 months. Mean survival since study entry was 6.1 months. In the 103 administrations we observed grade 3 or 4 toxicity on six occasions with diarrhea, five with neutropenia, and one with nausea and vomiting. Toxicity required dose reductions in five patients; in two of these patients treatment was stopped because of severe toxicity. No treatment related deaths occurred. CONCLUSION: CPT-11 as single-agent therapy is modestly effective against squamous cell cancer of the esophagus.

Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma.

Survivin, a new member of the family of apoptosis inhibitors, is expressed almost exclusively in proliferating cells, above all in cancers. Subcellular localisation and prognostic implications of the survivin protein have not yet been determined in oesophageal squamous cell carcinoma. The survival of 84 patients with oesophageal squamous cell carcinomas was correlated with the extent of immunohistochemical survivin expression in tumour cell nuclei. Tumours were scored positive when >5% cells stained positive. Patients were followed up for at least 5 years or until death. In normal oesophageal squamous cell epithelium, some cytoplasmic survivin expression was detected in the basal cells, whereas proliferating cells showed nuclear staining of survivin. Nuclear expression of survivin was also detected in 67 cancers (80%). The mean survival for patients of this group (28 months, range 20-36) was significantly less than that for patients without survivin expression in the tumour cell nuclei (108 months, range 62-154, P=0.003). Using univariate analysis, nuclear survivin expression (P=0.003), tumour depth (P=0.001), lymph node metastasis (P=0.003) and stage (P<0.001) were the best predictors of survival. In contrast, cytoplasmic survivin staining was noted in 53 (63%) tumours and had no prognostic relevance. In conclusion, the analysis of nuclear survivin expression identifies subgroups in oesophageal squamous cell cancer with favourable (survivin(-)) or with poor prognosis (survivin(+)). We suggest that the determination of nuclear survivin expression could be used to individualise therapeutic strategies in oesophageal squamous cell cancer in the future.