Management and Mid-Term Outcome After "Real SCIWORA" in Children and Adolescents.

STUDY DESIGN: Retrospective analysis. OBJECTIVE: The SCIWORA Syndrome (Spinal Cord Injury Without Radiographic Abnormalities) is a rare but potentially severe injury with a peak in childhood and adolescence. With a better understanding of injury patterns and advances in MRI, there is ongoing discussion regarding the "Real SCIWORA" syndrome, a clinical picture of neurologic deficits on clinical examination but absence of radiographic pathologies even on MRI. The purpose of this study was to evaluate mid-term clinical outcome and the psychological impact of the "Real SCIWORA." METHODS: In this retrospective analysis, we evaluated 32 patients treated for "Real SCIWORA" between 2007-2019. Inclusion criteria were: neurologic deficit after trauma, no other cerebral or skeletal injury and a lack of pathological findings in spinal MRI. All patients were followed until complete recovery from initial symptoms. 25/32 patients were re-evaluated after 6.9 years (1-14 years) using the Oswestry Disability Index, the Frankel Score, the EQ-5D score, and the Breslau Short Screening Scale for PTSD. RESULTS: Initial neurologic presentation ranged from Frankel Grade A-D. All patients recovered neurologically during 1-13 days to a Frankel Grade E. The analysis of HR-QoL revealed no difference between the cohort of SCIWORA patients and the German population norm, Oswestry Disability Index showed only minimal disabilities. 4/25 patients showed signs of PTSD. CONCLUSIONS: The "Real SCIWORA" syndrome is a diagnosis per exclusionem requiring a full spinal MRI to ensure exclusion of structural and potentially serious reasons of the neurologic impairment. Further clinical re-evaluation, psychological support seems to be essential. LEVEL OF EVIDENCE: IV-retrospective study.

Routine restaging after primary non-surgical treatment of laryngeal squamous cell carcinoma-a review.

PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.

[Diagnostic Criteria and Treatment of Hereditary Hemorrhagic Telangiectasia]. / Diagnostik und Behandlung der hereditären hämorrhagischen Teleangiektasie.

Hereditary hemorrhagic telangiectasia (HHT; Osler-Weber-Rendu syndrome; Morbus Osler) represents a syndrome affecting capillary vessels, leading to arteriovenous shunting. With an average worldwide prevalence of 1:5.000-8.000 HHT is considered an orphan disease. Arteriovenous shunts involve predominantly the nasal mucosa, the intestine, lung, liver and central nervous system. Epistaxis is the primary and most bothersome complaint of patients with HHT. A multistage therapeutic concept includes nasal ointment, laser therapy under local anesthesia and surgery under general anesthesia, as well as drug therapies. In addition, screening to determine affection of internal organs is carried out. Lesions that require therapy should be treated in an interdisciplinary setting. Treatment of lesions of the skin, oral and gastrointestinal mucosa and liver is carried out in regard to patients' symptoms, whereas vascular malformations of the lung and brain might need treatment without being symptomatic, due to possible life-threatening complications.

Peritoneal carcinomatosis of colorectal cancer is characterized by structural and functional reorganization of the tumor microenvironment inducing senescence and proliferation arrest in cancer cells.

Background : Peritoneal carcinomatosis (PC) is a terminal evolution from primary colorectal cancer (pCRC) associated with poor patient survival. Impact of the immune cell infiltrate on PC pathogenesis is unknown. Therefore, we characterized the immunological tumor microenvironment regarding proliferation, senescence and neovascularization. Methods : Formalin-fixed and paraffin-embedded (FFPE) tissue of PC and pCRC was examined by immunohistochemistry. Cells infiltrating resected tissue were isolated and analyzed by flow cytometry. PCR arrays detected the expression of genes relevant for helper T (TH) cell responses, like TH1, TH2 and TH17 response. Results : PC tumor cells demonstrate significantly lower proliferation rates than pCRC, but show significantly more senescence. PC is surrounded by significantly increased numbers of cytotoxic active Natural Killer (NK) cells, follicular helper T cells (TFH) and B cells, whereas pCRC shows more CD4+ TH cells, CD8+ cytotoxic T (TC) cells, eosinophilic granulocytes, TH17 and regulatory T (Treg) cells. PC is characterized by significantly increased interferon-γ (IFNγ), an upregulation of tumor necrosis factor (TNF) and the NK cell-regulating cytokine interleukin-15 (IL-15). An upregulation of angiogenesis-related genes, like vascular endothelial growth factor-A (VEGF-A), leads to severe neovascularization in PC. Correlations of PC results reveal that elevated numbers of interleukin-17 (IL-17) positive cells are associated with high cancer cell proliferation, whereas high numbers of IFNγ positive cells correlate with more tumor cells in senescence. Conclusion : The cellular immune reaction is modified during metastasis, inducing senescence in PC tumor cells. Immune surveillance in PC is facilitated by NK cells and high levels of IFNγ and TNF. Counteracting this effect, TFH and B cells combined with VEGF-A enhancement promote neovascularization in PC (Illustration 1). During metastasis from primary CRC to PC the immune cell infiltrate changes, accompanied by the induction of senescence in PC cancer cells (marked red): In pCRC, the antitumor immune response is facilitated by CD4+TH cells, CD8+TC cells and PRG2+ eosinophilic granulocytes. The premetastatic niche development is promoted by Treg cells and TH17 cells producing systemic factors like VEGF-A, TGF-ß and TNF. Along with TFH and B cells, as with a pro-tumor immune response, they support metastatic formation and lead to severe neovascularization in PC. This is counterbalanced by the IL-15-induced activation and proliferation of NK cells. The secreted cytokines IFNγ and TNF mediate immunosurveillance.