University of Cologne

About: University of Cologne is a education organization based out in Cologne, Germany. It is known for research contribution in the topics: Population & Gene. The organization has 32050 authors who have published 66350 publications receiving 2210092 citations. The organization is also known as: Universität zu Köln & Universitatis Coloniensis.

Histomorphologic Tumor Regression and Lymph Node Metastases Determine Prognosis Following Neoadjuvant Radiochemotherapy for Esophageal Cancer: Implications for Response Classification

Abstract: Esophageal cancer ranks among the 10 most frequent malignancies worldwide. Once diagnosed, the 5-year survival rate for these patients is about 10%.1 Surgery is the treatment of choice for most localized esophageal cancers. However, despite complete tumor resection and extensive lymphadenectomy, systemic and local recurrences are common and the 5-year survival rate ranges from 15% to 39%.2 Surgical results have improved in recent decades; however, most of this can be attributed to advances in preoperative staging, patient selection, refinement of surgical techniques, and postoperative care.3,4 The particularly poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments using neoadjuvant chemotherapy, radiotherapy, or radiochemotherapy in combination with surgery.5 The purported advantage of preoperative administration of chemotherapy, radiotherapy, or combined chemoradiation is that it may downstage the primary tumor, increase the resectability rate, eliminate micrometastases, and prolong survival.6 Results of larger randomized phase III trials using preoperative chemotherapy7–9 or radiochemotherapy10–12 were inconclusive; only 2 studies demonstrated a survival advantage for neoadjuvant treatment.9,10 Two recent meta-analyses of randomized trials showed modest but significant survival advantages for patients that received neoadjuvant chemotherapy13 or radiochemotherapy.14 In these trials, patients with a pathologic complete response have been consistently found to have impressive survival rates around 60%.2 According to the World Health Organization (WHO), clinical response is graded as complete, partial (>50% tumor regression), minor/no change (≤50% tumor regression), or progressive disease.15 Clinical response evaluations using endoscopic ultrasound and computed tomography (CT), however, have been shown to be highly inaccurate.16 In an effort to objectively evaluate response to neoadjuvant therapy, morphologic criteria have been defined for several cancers, including lung,17 stomach,18 and esophagus.19,20 Classification of regression based on the estimated percentage of vital residual tumor cells (VRTCs) was reported in non-small cell lung cancer patients following neoadjuvant radiochemotherapy.17 In a prospective trial, the presence of <10% VRTCs was shown to be of significant prognostic importance by multivariate analysis.21 We evaluated a modified regression classification system based on Junker et al,17 also taking into account clinical response evaluation according to WHO.15 Within a prospective observation trial consisting of patients receiving neoadjuvant radiochemotherapy for localized (cT2-4, Nx, M0) esophageal cancer, the potential for objective response classification was analyzed with regard to conventional “downstaging” as well as to prognostic implications concerning established clinical parameters.

Shutdown of class switch recombination by deletion of a switch region control element

Abstract: Upon activation, B lymphocytes can change the class of the antibody they express by immunoglobulin class switch recombination. Cytokines can direct this recombination to distinct classes by the specific activation of repetitive recombinogenic DNA sequences, the switch regions. Recombination to a particular switch region (s gamma 1) was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region. This result directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination. Mutant mice exhibit a selective agammaglobulinemia and may be useful in the assessment of the biological importance of immunoglobulin G1.

Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis

Abstract: BackgroundAdvanced systemic mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis. MethodsWe conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive systemic mastocytosis, 57 had systemic mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response. ResultsThe overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced systemic mastocytosis, KIT mutation status, or exposure...

Outcome in psychogenic nonepileptic seizures: 1 to 10-year follow-up in 164 patients.

Abstract: Our knowledge of longer term outcome in psychogenic nonepileptic seizures (PNESs) patients is limited; we know less still about factors predicting prognosis. This study was intended to describe outcome in a large cohort and to identify predictive clinical and psychological factors to generate new ideas for treatment. One hundred sixty-four adult patients with PNESs (66.7%) responded to outcome, personality, and psychosymptomatology questionnaires (Dimensional Assessment of Personality Pathology-Basic Questionnaire [DAPP-BQ], Dissociative Experiences Scale, and Screening Test for Somatoform Symptoms) a mean of 11.9 years after manifestation and 4.1 years after diagnosis of PNES. Additional clinical data were retrieved from hospital records. The responses showed that 71.2% of patients continued to have seizures and 56.4% were dependent on social security. Dependence increased with follow-up. Outcome was better in patients with greater educational attainments, younger onset and diagnosis, attacks with less dramatic features, fewer additional somatoform complaints, and lower dissociation scores. Better outcome was associated with lower scores of the higher order personality dimensions "inhibitedness," "emotional dysregulation," and "compulsivity" but not "dissocial behavior" (DAPP-BQ). Outcome in PNESs is poor but variable. Clinical and personality factors can be used to provide an individualized prognosis. By generating a patient-specific profile, they show particular maladaptive traits or tendencies that can identify goals for psychological therapy.