Laryngeal rare benign non-epithelial tumors and sarcomas emphasizing on chondrosarcomas: A literature review and a case presentation.

Laryngeal rare tumors include benign and malignant tumors of epithelial, non-epithelial, or mesenchymal origin. Chondrosarcomas are the most common mesenchymal malignant tumors of the larynx. We performed a literature review (Pubmed/Medline; PRISMA 2020) to detect the frequency of published studies from 2021 to April 2024 regarding benign and malignant epithelial, non-epithelial, or mesenchymal rare tumors of the larynx, emphasizing laryngeal chondrosarcoma (LC) cases. Articles including cases discussed before 2021 were excluded and articles without available English translations. We included 154 articles investigating rare tumors of the larynx, the majority of them discussed non-epithelial or mesenchymal entities (75 %). Specifically, a high proportion of studies examined benign non-epithelial or mesenchymal tumors (79.5 %) or mesenchymal rare malignancies (72 %) of the larynx concerning epithelial tumors in the last three years. Sarcomas were discussed in 74 % of mesenchymal laryngeal malignancies and more than 50 % of rare laryngeal tumor studies, and LC was discussed in ∼50 % of laryngeal sarcoma studies. LC studies reported 174 cases, 21 % of them of high-grade LC (II), including a new case of LC presented here in the supraglottic (grade II), which showed intense staining for the S100 marker. Our study highlights the awareness of rare laryngeal tumors emphasizing non-epithelial benign tumors and laryngeal sarcomas, including chondrosarcomas, as pathologic entities of the larynx. Although the majority of LC included low-grade neoplasms, a markedness proportion of LC cases was evaluated as high-grade. Future research approaches, including a range of low and high-grade tumors, would reveal prognostic markers or therapeutic targets for LC and other rare laryngeal malignancies of non-epithelial or mesenchymal origin.

Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme: a systematic review going beyond pathologic implications.

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation. Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression. Specifically, hypoxia is known to activate inducible factors, such as hypoxia-inducible factor 1alpha (HIF-1α), which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators, such as the vascular endothelial growth factor (VEGF). Here, we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data, as potential biomarkers of GBM prognosis and treatment efficacy. We performed a systematic review (Medline/Embase, and Pubmed database search was completed by 16th of April 2024 by two independent teams; PRISMA 2020). We evaluated methods of immunoassays, cell viability, or animal or patient survival methods of the retrieved studies to assess unbiased data. We used inclusion criteria, such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression, other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression, application of immunoassays for protein expression, and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression. We used exclusion criteria, such as data not reporting both HIF-1α and VEGF or prognosis. We included 50 studies investigating in total 1319 GBM human specimens, 18 different cell lines or GBM-derived stem cells, and 6 different animal models, to identify the association of HIF-1α/VEGF immunophenotypes, and with other prognostic factors, clinical and macroscopic data in GBM prognosis and therapeutic approaches. We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors, such as miR-210-3p, Oct4, AKT, COX-2, PDGF-C, PLDO3, M2 polarization, or ALK, leading to unfavorable survival. Reduced HIF-1α/VEGF expression correlates with FIH-1, ADNP, or STAT1 upregulation, as well as with clinical manifestations, like epileptogenicity, and a favorable prognosis of GBM. Based on our data, HIF-1α or VEGF immunophenotypes may be a useful tool to clarify MRI-PET imaging data distinguishing between GBM tumor progression and pseudoprogression. Finally, HIF-1α/VEGF immunophenotypes can reflect GBM treatment efficacy, including combined first-line treatment with histone deacetylase inhibitors, thimerosal, or an active metabolite of irinotecan, as well as STAT3 inhibitors alone, and resulting in a favorable tumor prognosis and patient survival. These data were supported by a combination of variable methods used to evaluate HIF-1α/VEGF immunophenotypes. Data limitations may include the use of less sensitive detection methods in some cases. Overall, our data support HIF-1α/VEGF's role as biomarkers of GBM prognosis and treatment efficacy.

Postoperative bioactive adrenomedullin is associated with the onset of ARDS and adverse outcomes in patients undergoing open thoracoabdominal aortic surgery.

Cytokine-mediated systemic inflammation after open thoracoabdominal aortic aneurysm (TAAA) repairs plays a pivotal role in disrupting circulatory homeostasis, potentially leading to organ dysfunction. The bioactive form of adrenomedullin (bio-ADM) is a peptide hormone with immunomodulatory and vasomotor effects, making it a potential diagnostic agent in these cases. This retrospective, bicentric study, conducted between January 2019 and December 2022, recruited 36 elective open TAAA repair patients in two German centres. Serum and plasma samples were collected at multiple time points to measure bio-ADM levels. The primary objective was to evaluate the association of bio-ADM levels with the onset of acute respiratory distress syndrome (ARDS), with secondary endpoints focusing on mortality and SIRS-related morbidity. Results showed a significant association between postoperative bio-ADM levels (12-48 h after surgery) and the onset of ARDS (p < .001), prolonged ventilation (p = .015 at 12h after surgery), atrial fibrillation (p < .001), and mortality (p = .05 at 24h). The biomarker was also strongly associated with sepsis (p = .01 at 12 h) and multi-organ dysfunction syndrome (MODS) (p = .02 at 24 h after surgery). The study underscores the potential utility of bio-ADM as a diagnostic tool for identifying patients at risk of postoperative complications following open TAAA repairs.

[Challenges and options for advanced training in surgery : An interdisciplinary position paper against the background of the hospital structural reform in Germany]. / Herausforderungen und Chancen für die chirurgische Weiterbildung : Ein fachgesellschaftsübergreifendes Positionspapier vor dem Hintergrund der Krankenhausstrukturreform.

BACKGROUND: Even now the further training in surgery faces considerable challenges. The planned hospital structural reform will result in new bureaucratic and organizational hurdles, which could lead to a considerable loss of quality in advanced surgical training across all disciplines. OBJECTIVE: The aim of this position paper is to describe the current and future challenges for advanced surgical training and to identify possible approaches and opportunities for the further development against the background of the planned hospital structural reform. MATERIAL AND METHODS: For the development of this position paper a committee of representatives of the Young Forums of the German surgical societies identified and critically discussed current problems and challenges of the present residency training system and formulated a list of demands for a sustainable residency training concept. RESULTS: The planned shift to outpatient treatment and centralization were identified as central challenges for surgical residency training. Surgical training must be considered consistently and from the outset in all political reform efforts. In addition to a transparent and cost-appropriate financing of residency training, we call for the involvement of all German surgical societies in the reform process. Furthermore, the social framework conditions for junior surgeons should be considered. CONCLUSION: The structural change in the hospital landscape in Germany, which is being forced by politicians, harbors the risk of a further loss of quality and experience in surgical treatment and training. At the same time, the planned hospital reform offers a unique opportunity to address existing problems and challenges in surgical training and to consider them as a starting point for structural changes which are fit for the future.

Novel non-invasive molecular signatures for oral cavity cancer, by whole transcriptome and small non-coding RNA sequencing analyses: Predicted association with PI3K/AKT/mTOR pathway.

INTRODUCTION: Identification of molecular biomarkers in the saliva and serum of oral cavity cancer patients represents a first step in the development of essential and efficient clinical tools for early detection and post-treatment monitoring. We hypothesized that molecular analyses of paired saliva and serum samples from an individual would likely yield better results than analyses of either serum or saliva alone. MATERIALS AND METHODS: We performed whole-transcriptome and small non-coding RNA sequencing analyses on 32 samples of saliva and serum collected from the same patients with oral squamous cell carcinoma (OSCC) and healthy controls (HC). RESULTS: We identified 12 novel saliva and serum miRNAs and a panel of unique miRNA and mRNA signatures, significantly differentially expressed in OSCC patients relative to HC (log2 fold change: 2.6-26.8; DE: 0.02-0.000001). We utilized a combined panel of the 10 top-deregulated miRNAs and mRNAs and evaluated their putative diagnostic potential (>87% sensitivity; 100% specificity), recommending seven of them for further validation. We also identified unique saliva and serum miRNAs associated with OSCC and smoking history (OSCC smokers vs. never-smokers or HC: log2 fold change: 22-23; DE: 0.00003-0.000000001). Functional and pathway analyses indicated interactions between the discovered OSCC-related non-invasive miRNAs and mRNAs and their targets, through PI3K/AKT/mTOR signaling. CONCLUSION: Our data support our hypothesis that using paired saliva and serum from the same individuals and deep sequencing analyses can provide unique combined mRNA and miRNA signatures associated with canonical pathways that may have a diagnostic advantage relative to saliva or serum alone and may be useful for clinical testing. We believe this data will contribute to effective preventive care by post-treatment monitoring of patients, as well as suggesting potential targets for therapeutic approaches.

Non-celiac Enteropathy and Olmesartan: An Essential Consideration.

Emerging evidence has shed light on non-celiac causes of enteropathy in recent years, presenting a diagnostic challenge for clinicians. This study discusses the diagnostic challenges related to non-celiac enteropathy, specifically focusing on olmesartan-induced enteropathy (OIE). A 73-year-old lady presented to the emergency department with a six-month history of watery diarrhea exacerbated by food intake and significant weight loss. The patient at admission was found to be dehydrated with severe hypokalemia and hypocalcemia. The extensive testing that was performed was unremarkable, including celiac disease panel, enteric panel, ova and parasites, Clostridium difficile, fecal calprotectin, and computed tomography of the abdomen and pelvis. A significant electrolyte imbalance was corrected at admission, and subsequent upper endoscopy investigation with duodenal biopsies revealed moderate to severe villi blunting with a significant intraepithelial infiltrate of CD3+ lymphocytes. A colonoscopy that was performed at the same time was unremarkable, with negative biopsies for microscopic colitis. Given the suspicion of OIE, olmesartan was discontinued. One-month follow-up revealed resolution of malabsorption, with electrolyte normalization and duodenal biopsies showing improved duodenitis. This study emphasizes the importance of considering medication history and ruling out other potential causes of enteropathy. Olmesartan is an angiotensin II receptor antagonist that is commonly prescribed for hypertension. However, in rare cases, it may induce enteropathy, which often remains underdiagnosed. This rare side effect may present as chronic diarrhea, weight loss, and signs of malabsorption. Interestingly, OIE presents with overlapping clinical and histopathological features to celiac disease and, therefore, may mislead physicians to an extensive diagnostic investigation. Greater awareness of medication-related diarrheal syndromes such as OIE should be promoted, given that simple discontinuation of the medication can lead to dramatic clinical improvement.

Short-Term Outcomes and Efficacy of Percutaneous Deep Vein Arterialization for No-Option Critical Limb Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous deep vein arterialization (pDVA) is considered a treatment modality in patients with no-option critical limb ischemia. However, there is still a paucity of evidence regarding its safety and efficacy. DATA SOURCES: MEDLINE (via PubMed), Embase and Web of Science databases as well as the CENTRAL registry up to the end of June 2023. METHODS: This review adhered to the PRISMA guidelines (PROSPERO registration no. CRD42023445171). The risk of bias was assessed using the methodological index for non-randomized studies (MINORS). Primary endpoints included technical success, overall survival and limb salvage during the follow-up. Amputation-free survival at 30 days, 6 months and 1 year as well as complete wound healing, major adverse limb events and reintervention were investigated as secondary outcomes. RESULTS: Five observational studies, comprising 208 patients (142 Rutherford class 5/77 Rutherford class 6), were included. MINORS revealed a low risk of bias. The meta-analysis reached a pooled technical success rate of 96.2% (95% CI: 91.5-98.4), an overall survival of 82.8% (95% CI: 70.5-95.2) and a limb salvage rate of 77.2% (95% CI: 65.2-89.1) during the follow-up. The amputation-free survival at 30 days, 6 months and 1 year was 87.8%, 68.7% and 65.6%, respectively. Furthermore, pDVA resulted in a complete wound healing rate of 53.4% (95% CI: 30.3-76.5). The pooled reintervention rate was as high as 46.7% (37.1-56.3%). CONCLUSIONS: PDVA seems a feasible bail-out strategy for patients with no option for routine treatment of CLTI. However, due to the small number of studies, the strength of the evidence is low.

Factors Associated with Early Mortality in Acute Type A Aortic Dissection-A Single-Centre Experience.

BACKGROUND: Acute aortic dissection type A (AADA) is a surgical emergency with relevant mortality and morbidity despite improvements in current management protocols. Identifying patients at risk of a fatal outcome and controlling the factors associated with mortality remain of paramount importance. METHODS: In this retrospective observational study, we reviewed the medical records of 117 patients with AADA, who were referred to our centre and operated on between 2005 and 2021. Preoperative, intraoperative, and postoperative variables were analysed and tested for their correlation with in-hospital mortality. RESULTS: The overall survival rate was 83%. Preoperatively, factors associated with mortality were age (p = 0.02), chronic hypertension (p = 0.02), any grade of aortic valve stenosis in the patient's medical history (p = 0.03), atrial fibrillation (p = 0.04), and oral anticoagulation (p = 0.04). Non-survivors had significantly longer operative times (p = 0.002). During the postoperative phase, mortality was strongly associated with acute kidney injury (AKI) (p < 0.001), acute heart failure (p < 0.001), stroke (p = 0.02), focal neurological deficits (p = 0.02), and sepsis (p = 0.001). In the multivariate regression analysis, the onset of postoperative focal neurological deficits was the best predictor of a fatal outcome after adjusting for ARDS (odds ratio: 5.8, 95%-CI: 1.2-41.7, p = 0.04). CONCLUSIONS: In this retrospective analysis, atrial fibrillation, oral anticoagulation, hypertension, and age were significantly correlated with mortality. Postoperatively, acute kidney injury, acute heart failure, sepsis, and focal neurological deficits were correlated with in-hospital mortality, and focal neurological deficit has been identified as a significant predictor of fatal outcomes. Early detection and interdisciplinary management of at-risk patients remain crucial throughout the postoperative phase.

Endovascular repair of the aortic arch.

Objectives: The gold standard for the treatment of pathologies of the aortic arch remains the open surgical reconstruction of the affected segments. However, endovas-cular treatment options have emerged that eliminate the need for invasive open surgery. Several endograft devices - with fenestrations or branches for the supraaortic vessels - are currently available to address different pathologies and anatomical variations. Parallel-graft techniques and in situ fenestrations expand the treatment options for emergent cases. In this selective review of the literature of 2020 and 2021, we summarize the current chances and challenges of endovascular aortic repair. Content: Reported mortality rates range from 0 to 13.2 %. Although technical success rates for fenestrated and branched devices are promising (98 %), stroke rates remain a relevant issue (10 and 3 % for BTEVAR and FTEVAR respectively). The reported technical success rate for in situ fenestrations is also encouraging (94 %) and the stroke rates acceptable (5 %). Parallel-graft techniques are associated with high early and late endoleak rates (early 76 %; late 31 %), but still hold a valuable place in the treatment of emergent cases or in bail-out situations. Summary and Outlook: The endovascular repair of the aortic arch expands the range of patients with pathologies of the arch eligible for treatment to those unfit for open surgery offering a minimally invasive, yet technically challenging procedure. More data and meta-analyses are needed to define the benefits and drawbacks of this promising treatment option in an aging population with increasing co-morbidities.