Project description:BACKGROUND:The endoscopic appearance of glottic erythroleukoplakias is non-predictive of their histopathology, potentially ranging from keratosis to invasive squamous cell carcinoma (SCC). The aim of this study was to assess a comprehensive workup for the one-step diagnosis and treatment of mid-cord erythroleukoplakias, using CO2 laser excisional biopsy. METHODS:We evaluated 147 untreated patients affected by 155 mid-cord erythroleukoplakias submitted to excisional biopsy by subepithelial (Type I) or subligamental cordectomy (Type II), across two academic institutions. Patients were evaluated by preoperative videolaryngostroboscopy, pre- and intraoperative videoendoscopy with biologic endoscopy (narrow band imaging, NBI, or the Storz professional image enhancement system, SPIES), either with or without intraoperative saline infusion into the Reinke's space. Adequacy of treatment was the primary outcome. RESULTS:The histopathologic diagnosis was keratosis in 26 (17%) cases, squamous intraepithelial neoplasia (SIN1-2) in 47 (30%), carcinoma in situ in 21 (14%), and SCC in 61 (39%) patients. The adequacy of treatment across the entire cohort was 89%. The intraoperative saline infusion procedure, facing not clearly suspicious lesions, raised the adequacy of treatment from 60% to 90% (p = 0.006). CONCLUSIONS:Excisional biopsy by Type I-II cordectomies, after a comprehensive diagnostic workup, should be accepted as an adequate and cost-effective treatment of unilateral mid-cord glottic erythroleukoplakias.
Project description:BackgroundOpioid analgesics are overprescribed after surgery. In August 2018, the authors replaced routine discharge opioid prescription with a nonsteroidal anti-inflammatory drug (NSAID) for patients who had a lumpectomy or excisional biopsy (lump/ex). This study compared patient-reported post-discharge pain scores for patients treated before and after the change in routine discharge medication.MethodsPatients were categorized based on treatment before and after a change in discharge medication as follows: study period 1 (routine opioids), study period 2 (routine NSAID). Pain severity was assessed with an electronic survey on postoperative days (PODs) 1 to 5. Multivariable generalized estimating equations tested the association between pain severity and discharge in the first versus the second study period.ResultsLump/ex was performed for 1606 patients between December 2017 and June 2019. Of these patients, 789 (49%) reported pain scores and were analyzed (328 in study period 1, 461 in study period 2). Opioid prescription at discharge decreased from 96% in period 1 to 14% (95% confidence interval [CI], 11-18%) in period 2. Only 1% of the patients discharged with NSAID were later prescribed an opioid. The maximum reported pain score on any POD for all the patients was severe for 30 patients (3.8%), moderate for 217 patients (28%), mild for 430 patients (54%), and none for 112 patients (14%). The estimated risk for moderate or greater pain on POD 1 was 36% for period 1 and 34% for period 2. The proportion of patients reporting moderate or greater pain was nonsignificantly lower for the patients treated in period 2 (odds ratio [OR], 0.91; 95% CI 0.67-1.22; P = 0.5).ConclusionsFor patients undergoing lump/ex, a clinically meaningful difference in reported post-discharge pain scores can be excluded with a change to routine NSAID at discharge. Patients undergoing lump/ex should not be routinely discharged with opioids.
Project description:BackgroundThe objective was to assess secretion of small extracellular vesicular microRNA (exo-miRNA) in head and neck squamous cell carcinoma (HNSCC) according to human papillomavirus (HPV) status, and determine the translational potential as a liquid biopsy for early detection.MethodsThis study employed a combination of cell culture and case-control study design using archival pretreatment serum. Small extracellular vesicles (sEV) were isolated from conditioned culture media and human serum samples via differential ultracentrifugation. miRNA-sequencing was performed on each sEV isolate.ResultsThere were clear exo-miRNA profiles that distinguished HNSCC cell lines from nonpathologic oral epithelial control cells. While there was some overlap among profiles across all samples, there were apparent differences in exo-miRNA profiles according to HPV-status. Importantly, differential exo-miRNA profiles were also apparent in serum from early-stage HNSCC cases relative to cancer-free controls.ConclusionsOur findings indicate that exo-miRNA are highly dysregulated in HNSCC and support the potential of exo-miRNA as biomarkers for HNSCC.
Project description:Background Access to the intraorbital optic nerve segment can be facilitated via a transcranial approach that allows access to the entire orbital cavity. The endoscopic endonasal approach (EEA) combined with a transconjunctival-medial orbitotomy represents an alternative technique to achieve the same goal. Objective Report a surgical technique that allows total resection of the intraorbital optic nerve with minimal trauma and excellent results. Further extend and define the limits and indications of the EEA to orbital surgery. Methods A patient with rapidly progressive, but asymmetric, vision loss underwent EEA for optic nerve biopsy. Due to the undetermined histopathological diagnosis and complete unilateral vision loss, diagnostic total optic nerve resection was indicated. The entire intraorbital length of the nerve was resected via an endoscopic endonasal transorbital approach combined with transconjunctival-medial orbitotomy. Results A 2-cm intraorbital nerve segment was sent for pathological examination. The patient maintained normal extraocular movements and experienced no complications. The postoperative course was uneventful and the patient was discharged the next day. Conclusion The EEA provides another option for access to the entire optic nerve. It is a safe and effective technique lacking cosmetic defects and providing an alternative corridor to traditional transcranial approaches to the orbit.
Project description:Infantile hemangiomas are common vascular tumors with a specific natural history. The proliferation and regression mechanism of infantile hemangiomas may be related to the multilineage differentiation ability of hemangioma stem cells, but the specific mechanism is not well elucidated. KIAA1429 is an N6 -methyladenosine methylation-related protein that can also exert its role in a methylation-independent manner. This study aims to explore the function of KIAA1429 in infantile hemangiomas. qRT-PCR, western blotting, and immunostaining were performed to verify the expression of KIAA1429. The endothelial and fibroblast-like phenotypes of hemangioma endothelial cells were detected after KIAA1429 knockdown and overexpression. The stemness properties of hemangioma endothelial cells and the underlying mechanism of KIAA1429 in hemangiomas were also investigated. Nude mouse models of infantile hemangiomas were conducted to ascertain the effects of KIAA1429 in vivo. The results showed that KIAA1429 was highly expressed in infantile hemangiomas, particularly in involuting hemangiomas. In vitro experiments confirmed that KIAA1429 inhibited the endothelial phenotype, enhanced the differentiation ability, and promoted the fibroblast-like phenotype of hemangioma endothelial cells by inducing endothelial cell transition to facultative stem cells. However, the effect of KIAA1429 on the potential target was shown to be independent of N6 -methyladenosine methylation modification. Mouse models further revealed that KIAA1429 could inhibit the proliferation and promote the regression of hemangiomas. In conclusion, this study found that KIAA1429 played an important role in the regression of infantile hemangiomas by enhancing the stemness of hemangioma endothelial cells and could be a potential treatment target for infantile hemangiomas.
Project description:Benign cardiac hemangiomas are rare tumors that may present in or out side of the heart, epicardium being the most common site. Echocardiography is the method of choice in diagnosing cardiac masses and though 3D TEE may seem to add exact information about the location, the time constraint in doing a comprehensive examination along with 3D rendering inside operation room may become an hindrance.
Project description:Infantile hemangiomas can cause significant morbidity during proliferation, yet there is no U.S. Food and Drug Administration-approved treatment. They are believed to form from hemangioma stem cells, which differentiate toward a hemangioma endothelial cell phenotype. Recently, propranolol has demonstrated effectiveness in treating complicated infantile hemangiomas. The authors hypothesize that propranolol facilitates their involution by altering cellular behavior in both hemangioma endothelial and stem cells.Hemangioma endothelial and stem cells were isolated from resected infantile hemangioma specimens. Cells were treated with 100 ?M propranolol for 48 hours, and apoptosis was determined by the presence of annexin V antibody. Proliferation of stem and endothelial cells was assessed after treatment with 50 or 100 ?M propranolol or vehicle, for 72 and 96 hours, respectively. Adipogenesis was induced in stem cells with and without propranolol. Pro-adipogenic genes PPAR?, PPAR?, C/EBP?, C/EBP?, C/EBP?, RXR?, and RXR? were analyzed by quantitative polymerase chain reaction.Annexin V levels were increased in propranolol-treated endothelial cells but not in stem cells. Proliferation of stem and endothelial cells was inhibited by propranolol in a dose-dependent manner. Propranolol-treated stem cells demonstrated accelerated adipogenesis when compared with untreated controls. Transcript levels of C/EBP? (p < 0.05), RXR? (p < 0.05), and PPAR? (p < 0.02) were significantly increased when treated with 50 or 100 ?M propranolol; and C/EBP? (p < 0.05), RXR? (p < 0.05), and PPAR? (p < 0.01) transcripts were increased when treated with 100 ?M propranolol. C/EBP? transcript levels remained unchanged at either dose.Propranolol increased apoptosis of hemangioma endothelial cells, but not stem cells, and accelerated adipogenesis of hemangioma stem cells. Thus, propranolol likely accelerates involution to fibrofatty residuum.
Project description:The murine excisional wound model has been used extensively to study each of the sequentially overlapping phases of wound healing: inflammation, proliferation and remodeling. Murine wounds have a histologically well-defined and easily recognizable wound bed over which these different phases of the healing process are measurable. Within the field, it is common to use an arbitrarily defined "middle" of the wound for histological analyses. However, wounds are a three-dimensional entity and often not histologically symmetrical, supporting the need for a well-defined and robust method of quantification to detect morphometric defects with a small effect size. In this protocol, we describe the procedure for creating bilateral, full-thickness excisional wounds in mice as well as a detailed instruction on how to measure morphometric parameters using an image processing program on select serial sections. The two-dimension measurements of wound length, epidermal length, epidermal area, and wound area are used in combination with the known distance between sections to extrapolate the three-dimension epidermal area covering the wound, overall wound area, epidermal volume and wound volume. Although this detailed histological analysis is more time and resource consuming than conventional analyses, its rigor increases the likelihood of detecting novel phenotypes in an inherently complex wound healing process.
Project description:The aim of this experiment was measure the influence of age on cutaneous wound healing using human subjects. Increaded age has been associated with delayed wound healing in mouse models and in humans. Gene expression was compared between excisional biopsy wounds from young and old subjects.
Project description:Tumor cells dissociate from the primary site and enter into systemic circulation (circulating tumor cells, CTCs) either alone or as tumor microemboli (clusters); the latter having an increased predisposition towards forming distal metastases than single CTCs. The formation of clusters is, in part, created by contacts between cell-cell junction proteins and/or cytokine receptor pairs with other cells such as neutrophils, platelets, fibroblasts, etc. In the present study, we provide evidence for an extravesicular (EV) mode of communication between pancreatic cancer CTCs and neutrophils. Our results suggest that the EV proteome of CTCs contain signaling proteins that can modulate degranulation and granule mobilization in neutrophils and, also, contain tissue plasminogen activator and other proteins that can regulate cluster formation. By exposing naïve neutrophils to EVs isolated from CTCs, we further show how these changes are modulated in a dynamic fashion indicating evidence for a deeper EV based remodulatory effect on companion cells in clusters.