Elisabeth Schellhaas

Bowel perforation in non-small cell lung cancer after bevacizumab therapy

SummaryBackground: Bevacizumab is increasingly used in combination with chemotherapy for treatment of unresectable non-small cell lung cancer. The aim of this report is to underline possible risks associated with this otherwise well-tolerated drug. Patient: A 69-year-old patient with metastatic non-small cell lung cancer was started on a palliative chemotherapy regimen containing carboplatin, paclitaxel, and bevacizumab. Results: After the second cycle of chemotherapy, the patient developed abdominal pain. On emergency laparotomy, there was diffuse perforation of the colonic wall, so the patient underwent a Hartmanns procedure with subtotal colectomy. Histopathological examination confirmed the diagnosis of ischemic colitis. Conclusion: Gastrointestinal perforation is a known adverse event of bevacizumab therapy which so far has occurred only in patients with predisposing risk factors. Our patient illustrates that there must always remain a high index of suspicion regarding bowel perforation in patients developing acute abdominal pain under bevacizumab therapy, even if they have no apparent risk factors.

Gangrenous intrathoracic appendicitis, a rare cause of right-sided chest pain: Report of a case

Diaphragmatic hernias are becoming increasingly common due to radiofrequency ablation of malignant liver tumors. Most patients eventually present with symptoms caused by bowel obstruction. A 54-year-old woman with pleuritic pain and fever had a right-sided enterothorax probably caused by hemihepatectomy several years before. The patient was diagnosed with perforated gangrenous intrathoracic appendicitis during an emergency laparotomy for suspected incarceration of her diaphragmatic hernia. She was treated with an appendectomy and suturing of her right hemidiaphragm. An acquired diaphragmatic hernia should therefore be surgically repaired as soon as it is diagnosed in order to avoid complications.

Mutations of the RET proto-oncogene in medullary thyroid cancer

Medullary thyroid cancer (MTC) is genetically determined by a RET proto-oncogene mutation in about a quarter of cases. The aggressiveness of the tumour can be predicted by the localisation of the mutation. The aim of this study was to analyse the distribution of diverse RET mutations in our own patient population. Since 1989, 63 patients have been primarily operated on in our department because of MTC or a genetic mutation predisposing towards the development of MTC. 26 patients were operated on prophylactically before the occurrence of symptomatic MTC. Those patients harboured mutations in the following codons of the RET proto-oncogene: codon 634: n=17; codon 618: n=2; codon 790: n=2; codon 791: n=1; exon 10 (codon not specified): n=1; localisation of the mutation not known: n=2. The oldest patients to undergo prophylactic surgery carried mutations in codons 791 (55 years), 648 (45 years), and 790 (37 years). Most patients operated on prophylactically (n=23) had only C cell hyperplasia or T1 tumours. Advanced tumours with lymph node metastases (n=2) were found only in patients with codon 634 mutations. The youngest patient with lymph node metastases was 9 years old. In 37 patients with symptomatic MTC, no mutation was found in 28 patients. Nine symptomatic patients harboured the following mutations: codon 634: n=4; codon 648: n=1; codon 804: n=1; hereditary MTC without known mutation: n=3. On average, tumours were more advanced than in patients who underwent prophylactic surgery. Our results confirm those of other authors that the specific mutation in the Ret proto-oncogene determines the course of malignant transformation of C cells. Prophylactic thyroidectomy in patients at risk should be done before the development of lymph node metastases; the ideal age for prophylactic surgery depends on the specific mutation.

M1630 Beyond Epithelial to Mesenchymal Transition: A Novel Role for the Transcription Factor Snail in Inflammation and Wound Healing

Introduction Snail, a transcription factor linked to epithelial to mesenchymal transition (EMT) during embryonic development and tumor progression, is associated with migration of cells. During inflammation and tissue injury, cell movement is also observed to provide the first line of defense against bacteria and to promote wound healing. Therefore, we studied the function of Snail in activated macrophages in a variety of inflammatory processes.

Kombinationstherapien mit Suramin beim Pankreaskarzinom

Suramin, a naphthyl urea derivative, inhibits growth of several tumours, among them ductal pancreatic adenocarcinoma, but its use as a single therapeutic agent is problematic due to its toxicity. Therefore, the aim of this study was to test the efficacy of a combination therapy of low dose suramin and docetaxel in pancreatic cancer. Rat ductal pancreatic adenocarcinoma cells (DSL6A) were incubated in the presence of increasing concentrations of suramin (in µg/mL: 0; 5; 10; 100) or docetaxel (in µg/mL: 0; 0.003; 0.015; 0.03; 3) or a combination of both drugs. Cell proliferation and viability were assessed after 72 hours. Docetaxel as well as suramin inhibited cell proliferation and viability in a dose-dependent way (p < 0.01). The highest concentrations used as monotherapy inhibited cell growth by 74 % (suramin) and 95 % (docetaxel), respectively. A combination of both drugs was more effective than each of the single agents given alone. Therefore, one can conclude that the addition of low dose suramin (in itself without any relevant effect on cell proliferation) enhances docetaxel efficacy in vitro. Further studies using an orthotopic tumour model of rat ductal pancreatic adenocarcinoma are necessary in order to confirm whether this combination therapy is of relevance in a preclinical therapeutic setting.

Intravitalmikroskopische Charakterisierung der Suraminwirkung im orthotopen immunkompetenten Rattenmodell des Pankreaskarzinoms

This study investigated the effects of Suramin, a naphthyl urea derivative, on tumor growth and spread in an immunocompetent rat model of pancreatic cancer, and analyzed the tumor vasculature by intravital microscopy. Rat pancreatic cancer cells (DSL-6A/C1) were incubated with Suramin. Proliferation was assessed after 72 hours. DSL-6A/C1 tumors were orthotopically induced in 72 Lewis rats. Animals received either Suramin or the vehicle. Treatment started 3 days after tumor induction. The pancreas was exteriorized for intravital microscopy 1, 4, and 8 weeks after tumor induction. Diameter, density, and permeability of tumor vessels were analyzed, as well as primary tumor volume, tumor dissemination, and microvessel density. Cancer cell proliferation was inhibited by Suramin dose dependently. All control animals developed extensive tumor growth, local infiltration, and distant metastasis. In contrast, there was no tumor detectable in half of the Suramin-treated animals after 8 weeks; the other animals harbored small tumors. Dissemination in treated animals was almost completely depressed after 8 weeks. Control animals displayed irregular tumor blood vessels. Suramin therapy resulted in a complete regression of tumor macrovessels and a significant reduction of microvessel density.