[Clinical, radiological, and histopathological features of pulmonary post-COVID syndrome : A form of autoimmune-mediated interstitial lung disease?] / Klinische, radiologische und histopathologische Merkmale des pulmonalen Post-COVID-Syndroms : Eine Form der autoimmunvermittelten interstitiellen Lungenerkrankung?

BACKGROUND: About 10% of patients develop persistent symptoms after mild/moderate COVID-19. We have previously reported detection of antinuclear autoantibodies/extractable nuclear antigens (ANA/ENA) in patients with severe COVID-19. OBJECTIVES: The aim of this small pilot study was to characterize long-/post-COVID and to evaluate possible similarities between lung involvement in long-/post-COVID and connective tissue disease (CTD). METHODS: We prospectively enrolled 33 previously healthy patients with persistent pulmonal symptoms after mild/moderate COVID-19 without hospitalization (median age, 39 years). We performed clinical evaluation including pulmonary function tests, computed tomography (CT), and serology for ANA/ENA. In 29 of 33 patients, transbronchial biopsies (TBBs) were taken for histopathological assessment. RESULTS: Most patients presented with disturbed oxygen pulse in spiroergometry and slight lymphocytosis in bronchoalveolar lavage (BAL) fluid. The CT pattern showed bronchial wall thickening and increased low-attenuation volume. Autoantibodies were detected in 13 of 33 patients (39.4%). Histopathological assessment showed interstitial lymphocytosis with alveolar fibrin and organizing pneumonia. Ultrastructural analyses revealed interstitial collagen deposition. CONCLUSION: While histopathology of pulmonary long-/post-COVID alone is unspecific, the combination with clinical and radiological features together with detection of autoantibodies would allow for a diagnosis of interstitial pneumonia with autoimmune features (IPAF). Since we observe interstitial collagen deposition and since IPAF/CTD-ILD might progress to fibrosis, the persistence of autoantibodies and possible fibrotic change should be closely monitored in autoantibody-positive long-/post-COVID patients.

[Regulator proteins of actin dynamics as possible targets of antineoplastic therapies]. / Regulatorproteine des Aktin-Umbaus als mögliche Zielstrukturen antineoplastischer Therapien.

BACKGROUND: The ability of tumor cells to leave the primary tumor is prerequisite for metastatic spread. In previous studies, we identified regulator proteins of actin reorganization with essential functions in both synaptogenesis and tumor cell migration. OBJECTIVE: The aim of the studies summarized in this article is to identify signaling pathways associated with actin-related proteins that might represent potential molecular targets for antiinvasive and/or antineoplastic therapies. MATERIALS AND METHODS: We used immunohistochemical analyses of protein expression as well as in vitro techniques (cell culture, fluorescence microscopy, RNAi-based knockdown of protein expression, protein biochemistry and in vivo animal experiment substitutes). RESULTS: We show that phosphorylation of Abelson interactor 1 (Abi1) is essential for the adhesion and invasion of colorectal carcinoma cells and might be targeted by the tyrosine kinase inhibitor STI571/Glivec®. HnRNP K, a protein interaction partner of Abi1, is upregulated in malignant melanoma in response to ionizing radiation; this upregulation is impaired upon application of the MEK inhibitor PD98059, enhancing radiosensivity of melanoma. Edelfosin, an alkyl-lipid blocker of the Abi1 interaction partner SK3, inhibits invasion of urothelial carcinoma cells. CONCLUSION: The studies summarized in this overview confirm a central role for the investigated proteins in tumor cell invasion and resistance to antineoplastic therapies and identify possible molecular targets for novel therapeutic compounds.

Pedunculated, well differentiated liposarcoma of the oesophagus mimicking giant fibrovascular polyp.

We present a rare case of a big oesophageal liposarcoma causing dysphagia and weight loss in a 75-year-old patient. Endoscopically, a pedunculated lesion with subtotal obstruction of the oesophageal lumen had been detected and thoracoabdominal oesophageal resection with gastric sleeve reconstruction was performed. Surprisingly, a liposarcoma of the oesophagus was revealed on histopathological analysis, showing MDM2 overexpression. Oncological follow-up has been uneventful and the patient remains in good clinical shape at 15 months after surgery.

[Metastasis and progression mechanisms of soft tissue tumors]. / Metastasierung und Progressionsmechanismen von Weichteiltumoren.

Invasion and metastatic dissemination of tumor cells defines prognosis not only in patients with epithelial, but also mesenchymal neoplasms. Early and clinically inapparent micrometastases occur in many patients, and the risk for metastasis correlates with the tumor subtype and histologic tumor grade. In recent years and analogous to the situation in epithelial tumors, mechanisms of tumor cell dissemination in soft tissue tumors have been increasingly understood, and it has been shown that reorganization of the actin cytoskeleton plays a key role in these processes. This review summarizes current knowledge on the mechanisms of progression and metastasis of soft tissue tumors and points out possible targets for novel anti-invasive and anti-metastatic therapies.

[Importance of cellular tight junction complexes in the development of periprosthetic leakage after prosthetic voice rehabilitation]. / Bedeutung zellulärer Tight-junction-Komplexe bei der Entwicklung einer periprothetischen Leckage bei stimmprothetischer Versorgung.

BACKGROUND: The use of voice prostheses is currently the gold standard in voice rehabilitation after total laryngectomy. This method combines low complication rates and excellent rehabilitation results; however, approximately 30% of patients show periprosthetic leakage or severe fistula enlargement after laryngectomy and prosthetic voice restoration within the first 4 years. The development of this enlargement is controversially discussed in the literature but recently published studies have shown that high esophageal reflux plays a key role in this process, which leads to an inflammatory reaction and disturbs the intercellular tight junctions in the sense of an epithelial mesenchymal transition (EMT). MATERIAL AND METHODS: A total of 44 patients underwent 24 h pH monitoring, a sample biopsy from the region of the fistula and a subsequent biomolecular examination for intracellular junction proteins as well as a correlation between the severity of reflux and tracheoesophageal fistula problems before and after antireflux therapy with proton pump inhibitors (PPI). RESULTS: Immunohistochemical staining revealed decreases in membrane E-cadherin and ß-catenin and a significant increase in the cytoplasmic fraction, depending on the severity of inflammation in the fistula tissue. In patients with an improvement of clinical fistula problems under oral PPI treatment an increase of membrane E-cadherin could be shown, whereas patients with persisting fistula enlargement demonstrated a further decrease of E-cadherin. CONCLUSION: The data indicate a central role of EMT in the development of fistula enlargement after total laryngectomy. Patients with periprosthetic leakage showed a loss of membrane bound E-cadherin and ß-catenin with an up-regulation of vimentin expression. In patients with mild or no leakage problems EMT could be resolved by aggressive antireflux treatment, whereas patients without any effect of PPI treatment on the fistula showed no reversal of EMT. These data contribute to the understanding of treatment resistant fistula enlargement after total laryngectomy.

[Abelson interactor 1 (Abi1) in colorectal cancer. From synaptic plasticity to tumor cell migration]. / Abelson interactor 1 (Abi1) im kolorektalen Karzinom. Von der synaptischen Plastizität zur Tumorzellmigration.

BACKGROUND: Invasion and metastatic dissemination of tumor cells defines the prognosis of patients with colorectal cancer (CRC). The Abelson interactor 1 (Abi1), a 65 kD substrate of the eponymous Abelson tyrosine kinase, interacts with phosphatidylinositol-3-kinase (PI3K) and heterogeneous nuclear ribonucleoprotein K (hnRNP K) and is a key regulator of cytoskeletal reorganization during synaptic maturation and cellular migration. AIM: The aim of this study was the analysis of Abi1 expression patterns and to elucidate the role in cytoskeletal reorganization in colorectal carcinoma cells. MATERIAL AND METHODS: The methods used in this study were immunohistochemistry; immunofluorescence microscopy; liposomal transfection and protein analysis by Western blotting. RESULTS: The results showed that Abi1 is expressed at the invasive front of colorectal carcinomas and localizes to the leading edge of lamellipodia in cultured colorectal carcinoma cells. A phosphorylated isoform of Abi1 that stains positively in these microcompartments disappears after treatment with the tyrosine kinase inhibitor STI571 (Glivec®). The RNA interference (RNAi) approach knockdown of Abi1 as well as treatment with STI571 induce a shift in cellular morphology from broad lamellipodia-like to thin filopodia-like cellular protrusions. DISCUSSION: The initial results support a central role for phosphorylated Abi1 in the formation of lamellipodia-like cellular protrusions as a prerequisite for cellular migration of colorectal carcinoma cells. As phosphorylation of Abi1 could be pharmaceutically targeted with STI571, this indicates a possible therapeutic option to prevent the gain of a metastatic phenotype in colorectal cancer. This possibility will be further evaluated in ongoing research.

[Human papillomavirus in squamous cell cancer of the head and neck. A study at the Ulm Military Hospital, Germany]. / Humane Papillomavirusinfektionen bei Plattenepithelkarzinomen des Kopf- und Halsbereichs. Eine Untersuchung am Krankengut des Bundeswehrkrankenhauses Ulm.

There is increasing evidence worldwide that human papillomavirus is a major risk factor for head and neck cancer. Only few studies on this association have been performed in Germany to date. For the purposes of the present study, tumor specimens from 223 patients with squamous cell cancer of the oral cavity, oropharynx, hypopharynx and larynx were analyzed for HPV DNA and p16INK4a expression. The prevalence of HPV genotype 16 (HPV16) DNA in the study population was 17.5%. Further high-risk HPV types were not detected. All HPV16-positive tumors showed intense p16INK4a expression. HPV16 prevalence was highest in tonsillar carcinoma (37.5%) and lowest in laryngeal cancer (2.8%). We observed a significantly higher incidence of cervical lymph node metastases in patients with HPV16-positive tonsillar carcinoma in comparison to HPV-negative tumors (p < 0.016). Tobacco and/or alcohol consumption was significantly lower in patients with HPV-positive tumors (p < 0.0001).