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Τρίτη 14 Σεπτεμβρίου 2021

Expression of the cancer stem cell marker OCT4 is associated with worse prognosis and survival in cutaneous melanoma

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imageCutaneous melanoma has an aggressive clinical presentation, showing rapid rate of growth and metastatic dissemination due to the permanence of cancer stem cells. The present study was to evaluate the expression of the self-renewal regulatory factor and the clinical significance of the transcription factor OCT4 in melanoma. Melanoma tissues were stained by immunohistochemistry and the correlation between the expression of this marker was determined through clinical–pathological variables and survival outcomes. Positive expression of nuclear and cytoplasmic OCT4 was observed in 49% and 41.2% of cases, respectively. T he positive expression of nuclear OCT4 in melanoma was significantly associated with prognostic factors, such as Breslow depth, Clark's level, ulceration and metastasis. Survival of patients was 56% compared to positive nuclear OCT4 expression and 94.2% when compared to the low expression of the gene. Nuclear OCT4 positive genotype indicated aggressive tumor behavior with a worse clinical outcome, which indicates OCT4 as a useful biomarker in the prognosis of melanoma.
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Expression of cathepsins B and D by cancer stem cells in head and neck metastatic malignant melanoma

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imageWe have previously demonstrated cancer stem cell (CSC) subpopulations in head and neck metastatic malignant melanoma (HNmMM), and the expression of components of the renin–angiotensin system (RAS) by these CSCs. Cathepsins B, D and G are involved in carcinogenesis and constitute bypass loops of the RAS. This study investigated the expression and localization of cathepsins B, D and G, in relation to these CSCs. Immunohistochemical staining demonstrated expression of cathepsins B, D and G in HNmMM sections from all 20 patients. Western blotting confirmed the presence of cathepsins B and D proteins in all six HNmMM tiss ue samples and four HNmMM-derived primary cell lines. RT-qPCR showed transcript expression of cathepsins B, D and G in all six HNmMM tissue samples, and cathepsins B and D but not cathepsin G in all four HNmMM-derived primary cell lines. Enzymatic activity assays demonstrated cathepsins B and D were active in all six HNmMM tissue samples. Immunofluorescence staining performed on two of the HNmMM tissue samples demonstrated expression of cathepsins B and D by the CSCs, and cathepsin G by cells within the peritumoral stroma. Our novel findings suggest the possibility of targeting these CSCs by modulation of paracrine RAS signaling.
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Low-dose ipilimumab combined with anti-PD-1 immunotherapy in patients with metastatic melanoma following anti-PD-1 treatment failure

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imageCombined immunotherapy is associated with a significant risk of severe and potentially fatal immune-related adverse events (irAEs). Therefore, we retrospectively analyzed the side profile and efficacy of low-dose ipilimumab (1 mg/kg, IPI1) combined with anti-PD-1 immunotherapy in patients who progressed after anti-PD-1 monotherapy. Nine patients with unresectable stage III or IV melanoma treated with combined low-dose ipilimumab (1 mg/kg, IPI1) and anti-PD-1 immunotherapy, following progression after anti-PD-1 treatment, were identified. Treatment response and irAEs were recorded. Grade 3 irAEs occurred in one-third of pat ients. Interestingly, there were no grade 4 or 5 irAEs. In fact, four out of the nine patients experienced no irAEs at all. One patient discontinued combined immunotherapy due to immune-related colitis. The mean time to the onset of grade 3 irAEs was 14.3 weeks. The objective response rate was 33.3% and a disease control rate of 66.7% was achieved. Median progression-free survival (PFS) was 5.7 months and median overall survival (OS) was 21.6 months. The median PFS when IPI1 and anti-PD-1 treatment was administered in the second-line setting was not reached, but only 2.8 months when used in subsequent treatment settings. Combined IPI1 and anti-PD-1 immunotherapy was well tolerated. Its use in the third-line or above setting was associated with a significantly poorer prognosis than in the second-line setting. Larger, prospective studies are required to evaluate the safety and efficacy of this dosing regimen following anti-PD-1 treatment failure.
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Association of Quality of Life Measures and Otolaryngologic Care in Cystic Fibrosis Patients

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Ann Otol Rhinol Laryngol. 2021 Sep 11:34894211045636. doi: 10.1177/00034894211045636. Online ahead of print.

ABSTRACT

OBJECTIVES: Appropriate management of chronic rhinosinusitis (CRS) among patients with cystic fibrosis (CF) is important in improving quality of life. Otolaryngologists play a critical role in reducing CRS symptom burden. This study seeks to evaluate the role of patient-reported quality-of-life measures in guiding interventions for CF-related sinus disease.

METHODS: We performed a prospective, cross-sectional study of 105 patients presenting to a CF-accredited clinic between July and September 2018. Demographic data and sinus surgery history were collected, in addition to Sino-Nasal Outcome Test (SNOT-22) and Questionnaire of Olfactory Disorders (QOD-NS) scores. Statistical analysis was conducted using correlation and non-parametric Mann-Whitney U tests.

RESULTS: Baseline well-care visits accounted for 71.4% of all clinical evaluations. Prior otolaryngology intervention was noted in 69 (66%) patients, where the majority of these patients (63/69; 91%) underwent endoscopic sinus surgery (ESS). Patients with a history of otolaryngology intervention had an average SNOT-22 score of 33.2 (SD = 20.6) compared to 24.9 (SD = 18.5) for patients without prior intervention (P = .048). The average QOD-NS score was 5.5 (SD = 6.4) among patients referred to otolaryngologists and 3.1 (SD = 5.7) for non-referred patients (P< /i> = .012). SNOT-22 and QOD-NS scores were modestly correlated (R of .43).

CONCLUSION: CF patients with symptoms resulting in worse quality-of-life assessments were more likely to have established coordinated care with an otolaryngologist. Further validation of the utility of SNOT-22 and QOD-NS questionnaires as care coordination metrics is necessary in the CF population.

PMID:34514873 | DOI:10.1177/00034894211045636

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Objective Analysis Of Voice Quality In Patients With Thyroid Pathology

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Abstract

Background

One of the symptoms reported by patients with thyroid pathology are the changes in voice. The percentages of vocal alterations found in the literature vary between 16.7% and 68%. Such variability can be explained by different assessment methods used and their reliability.

Objective

The goal of this study is to analyze the voice in patients with thyroid pathology through two objective indexes with great diagnostic accuracy. Overall vocal quality was evaluated with the Acoustic Voice Quality Index (AVQI v.03.01) and the breathy voice with the Acoustic Breathiness Index (ABI).

Method

Observational case-control study of fifty-eight subjects, 29 controls and 29 thyroidectomy candidates. All participants with thyroid pathology completed the Spanish version of Voice Handicap Index-10. Also, patient complaints relating to possible laryngeal dysfunction were assessed through closed questions. A sustained vowel and three phonetically balanced sentences were recorded for each subject (118 samples). AVQI v.03.01 and ABI were assessed using the Praat program. Two raters perceptually evaluated each voice sample by using the Grade parameter of GRABS scale.

Results

Acoustic analysis shows that 55.17% of subjects present values above the pathological threshold of the AVQI, and 58.62% above that of the ABI. Results of the Student's test comparisons of the AVQI and ABI values between the control group and the thyroid group show significantly higher values of AVQI (t[56]=-3.85, p<0.001) and ABI (t[54.39]=-4.82, p<0.001) in thyroidectomy candidates.

Conclusion

A mild decrease in vocal quality is part of the symptomatology presented by thyroidectomy candidates.

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Bone Cement Cranioplasty Reduces Cerebrospinal Fluid Leak Rate after Microvascular Decompression: A Single-Institutional Experience

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J Neurol Surg B Skull Base. 2021 Oct;82(5):556-561. doi: 10.1055/s-0040-1715607. Epub 2020 Aug 20.

ABSTRACT

Background Microvascular decompression (MVD) is a common surgical treatment for cranial nerve compression, though cerebrospinal fluid (CSF) leak is a known complication of this procedure. Bone cement cranioplasty may reduce rates of CSF leak. Objective To compare rates of CSF leak before and after implementation of bone cement cranioplasty for the reconstruction of cranial defects after MVD. Methods Retrospective chart review was performed of patients who underwent MVD through retrosigmoid craniectomy for cranial nerve compression at a single institution from 1998 to 2017. Study variables included patient demographics, medical history, type of closure, and postoperative complications such as CSF leak, meningitis, lumbar drain placement, and ventriculoperitoneal shunt insertion. Cement and noncement closure groups we re compared, and predictors of CSF leak were assessed using a multivariate logistic regression model. Results A total of 547 patients treated by 10 neurosurgeons were followed up for more than 20 years, of whom 288 (52.7%) received cement cranioplasty and 259 (47.3%) did not. Baseline comorbidities were not significantly different between groups. CSF leak rate was significantly lower in the cement group than in the noncement group (4.5 vs. 14.3%; p < 0.001). This was associated with significantly fewer patients developing postoperative meningitis (0.7 vs. 5.2%; p = 0.003). Multiple logistic regression model demonstrated noncement closure as the only independent predictor of CSF leak (odds ratio: 3.55; 95% CI: 1.78-7.06; p < 0.001). Conclusion CSF leak is a well-known complication after MVD. Bone cement cranioplasty significantly reduces the incidence of postoperative CSF leak and other complications. Modifiable risk factors such as body mass index were not associated with the development of CSF leak.

PMID:34513562 | PMC:PMC8421130 | DOI:10.1055/s-0040-1715607

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Heterogeneity in Outcome Reporting in Endoscopic Endonasal Skull Base Reconstruction: A Systematic Review

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J Neurol Surg B Skull Base. 2021 Oct;82(5):506-521. doi: 10.1055/s-0040-1714108. Epub 2020 Aug 7.

ABSTRACT

Objective Presently, there are no standards for reporting outcomes of endoscopic endonasal skull base reconstruction (ESBR). This is problematic as a lack of consistent reporting makes synthesizing findings in systematic reviews and meta-analysis challenging. Thus, the aim of this study was to systematically review and describe the patterns of reporting outcomes in ESBR as a foundation for developing reporting guidelines. Study Design Present study is a systematic review. Methods Embase, PubMed, CINAHL, Cochrane Library, and Web of Science were searched for all publications with ≥25 patients and a focus on ESBR. The reporting patterns of each study's variables and outcomes were assessed. Results A total of 112 studies were included in the review. The most commonly reported demographic variables were the numb er of included patients ( n = 112, 100%) and types of pathologies treated ( n = 104, 92.9%). Meanwhile, the most routinely described preoperative variable was history of prior treatment ( n = 48, 42.9%). Type of reconstruction was a commonly reported intraoperative variable ( n = 110, 98.2%), though the rate of intraoperative cerebrospinal fluid (CSF) leak was noted in only 76 studies (67.9%). With regard to postoperative outcomes, postoperative CSF leak rate was routinely provided ( n = 101, 90.2%), but reporting of other surgical complications was more inconsistent. Ultimately, of the 43 variables and outcomes reviewed, a median of 12 (range: 4-22) was reported in each study. Conclusion There is significant heterogeneity in the outcomes reported in studies relating to ESBR. This highlights the need for the development of standard reporting guidelines to minimize bias and improve interstudy comparability.

PMID:34513556 | PMC:PMC8421125 | DOI:10.1055/s-0040-1714108

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