Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Sunday, October 31, 2021

Role of metronomic therapy for advanced oral cancers and predictors of response: A multi‐institutional feasibility study

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Abstract

Background

In an era of targeted therapies, patients with cancer in resource-constraint countries continue to struggle to find affordable care.

Methods

The present study is a multicenter prospective single-arm study. Patients with expected delay in surgery, unresectable or metastatic cancers, and patients not suitable for surgery or conventional chemotherapy were included. Oral methotrexate 15 mg/m2 once a week and oral celecoxib 200 mg twice daily was used for metronomic therapy.

Results

At 8 weeks, a clinically complete response was seen in 2.5%, partial response in 46.6%, stable disease in 39.8%, and disease progression in 11%. Size less than 4 cm, alveolobuccal subsite, and well-differentiated histology were significantly associated with no disease progression.

Conclusion

Constraint-adapted approach of using methotrexate and celecoxib is economical with good compliance, minimal toxicity, and good efficacy. It is feasible for use in diverse settings. Individualized selection of patients based on response predictors may maximize metronomic therapy's benefit.

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Trainee participation does not adversely affect the safety of thyroid surgery: A systematic review and meta‐analysis

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Abstract

Surgical traineeship is essential but must be safe for patients. In thyroid surgery, surgeon volume correlates with improved clinical/economic outcomes. However, it is presently unclear how far does trainee participation affect post-thyroidectomy complication rates in real-world and randomized data. We systematically searched four databases for associations of trainee participation with any post-thyroidectomy outcome. We conducted univariate meta-analyses, sensitivity analyses, and assessed publication bias qualitatively and quantitatively. We included 1 randomized and 15 observational studies from 3755 records, comprising 34 774 thyroid surgical patients. Trainee participation was associated with 12 min longer operative time, but not higher complication rates (hypoparathyroidism, recurrent laryngeal nerve palsy, hematoma, blood loss, return to operating room, hospitalization duration, readmission, and mortality). Sensitivity, publication bias, and multivariate analyses did no t change our findings. Real-world and limited randomized data suggest that trainee participation in thyroid surgery is safe, given adequate consultant supervision and appropriate case selection.

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Otolaryngology Utilization in Patients With Achondroplasia: Results From the CLARITY Study

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Objectives/Hypothesis

To quantify otolaryngologic surgery utilization in patients with achondroplasia, and to identify any changes in utilization over the past four decades.

Study Design

Retrospective cohort study.

Methods

A retrospective cohort study of 1,374 patients with achondroplasia enrolled in the CLARITY retrospective cohort study at four centers of multi-specialty care for patients with achondroplasia. Otolaryngologic surgeries are presented by birth cohort decade. The main outcomes were number of primary and additional otolaryngologic procedures; age at surgery; likelihood of repeated surgery; temporal trends in surgical utilization.

Results

In this cohort of 1,374 patients with achondroplasia, 620 (45.1%) had pharyngeal surgery at least once, 150 (10.9%) had pharyngeal surgery on more than one occasion, and patients who had adenoidectomy first were 2.68 times more likely to require a second pharyngeal surgery than those who had adenotonsillectomy. Seven hundred and seventy-nine (56.7%) had tympanostomy tubes placed at least once, and 447 (32.5%) had tympanostomy tubes placed more than one time. Age at first pharyngeal surgery decreased by 1.2 years per birth cohort decade, and age at tympanostomy tube placement decreased by 1.1 years per decade.

Conclusions

Patients with achondroplasia often require otolaryngologic surgery, particularly adenoidectomy and/or tonsillectomy as well as tympanostomy tube placement. Such surgery is performed now more frequently and at younger ages than in earlier decades. While otolaryngologic disease associated with achondroplasia is now recognized earlier and treated more frequently, long-term outcome studies are needed.

Level of Evidence

3 Laryngoscope, 2021

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Prophylactic Central Neck Dissection for Clinically Node‐Negative Papillary Thyroid Carcinoma

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Objective

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that scrutinized the oncological benefits and postsurgical complications of total thyroidectomy (TT) plus prophylactic central neck dissection (pCND) versus TT alone among clinically node-negative (cN0) papillary thyroid cancer (PTC) patients.

Methods

We screened five databases from inception to September 4, 2021 and evaluated the risk of bias of the eligible studies. We pooled dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI).

Results

Overall, we included 5 RCTs with low risk of bias comprising 795 patients (TT plus pCND = 410 and TT alone = 385). With regard to efficacy endpoint, the rate of structural loco-regional recurrence did not significantly differ between both groups (n = 4 RCTs, RR = 0.49, 95% CI [0.19, 1.27], P = .14). With regard to safety endpoints, the rates of hypoparathyroidism (n = 5 RCTs, RR = 1.48, 95% CI [0.73, 2.97], P = .27), recurrent laryngeal nerve injury (n = 5 RCTs, RR = 1.34, 95% CI [0.59, 3.03], P = .48), and bleeding (n = 3 RCTs, RR = 1.75, 95% CI [0.42, 7.26], P = .44) did not significantly differ between both groups.

Conclusion

For cN0 PTC patients, there was no significant difference between TT plus pCND and TT alone with regard to the rate of structural loco-regional recurrence or frequency of postsurgical complications. Adaptation of pCND in cN0 PTC patients should be contemplated by taking into consideration the clinical oncological benefits and rate of postsurgical adverse events.

Level of Evidence

1 Laryngoscope, 2021

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Synthetic Triterpenoid RTA‐408: Limits Radiation Damage to Normal Tissue

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Objectives/Hypothesis

To assess the efficacy and mechanism of action of a novel approach to mitigate acute and chronic radiation toxicity in a validated animal model.

Study Design

Randomized, prospective study using an in vivo rat model.

Methods

Experimental animal study utilizing Sprague–Dawley rats divided into three cohorts: 1) radiation + dimethyl sulfoxide (DMSO) (inert vehicle); 2) radiation + RTA-408 (therapeutic drug); and 3) no radiation + DMSO. All animals in the radiation cohorts underwent 40 Gy of radiation with subsequent inferior epigastric axial rotational flap 30 days later in all cohorts with percentage of flap necrosis and vascular density calculated by blinded observers. In a second experiment, an additional three cohorts, underwent serial punch biopsies of the abdominal skin before, during, and after radiation and drug/vehicle control treatment. Transcriptome analysis utilizing gene set enrichment analysis and digital polymerase chain reaction were performed at various time points.

Results

The first experiment revealed average flap necrosis of 20% (95% confidence interval [CI] 16–45) in the radiation control group, 3% (95% CI 0–11) in the nonirradiated control, and 3% (95% CI 0.2–10) in the radiation group treated with RTA-408. Vascular density was preserved in the treatment group as compared to the radiated control. Nine rats were included in the second experiment, and transcriptome analyses in the treatment group revealed robust activation of antioxidant pathways with induced expression of genes associated with hypoxia and adipogenesis/angiogenesis.

Conclusions

Administration of RTA-408 during radiation treatment in a rat model resulted in transcriptome changes which appear to mitigate the toxic effects of radiation, preserving capillary networks and improving flap survival and tissue healing after subsequent surgery.

Level of Evidence

Foundational Evidence, Animal Research Laryngoscope, 2021

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Grading System and Surgical Strategy for Temporal Bone Diffuse‐Type Tenosynovial Giant Cell Tumor

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Objectives

To develop a novel grading system and appropriate surgical approaches for patients with diffuse type tensosynovial giant cell tumor (D-TGCT) of the temporal bone.

Study Design

Retrospective cohort study.

Methods

We retrospectively reviewed 31 patients with temporal bone D-TGCT between June 2012 and July 2021. All patients underwent comprehensive clinical evaluations, including clinical presentations, hearing threshold, imaging studies, surgical approaches, and prognosis. A grading system was developed based on the tumor location and adjacent neurovascular structures involvement according to imaging and intraoperative findings.

Results

In this study, grade II tumors were the most common (13/31), followed by grades I (7/31), III (7/31), and IV (4/31) tumors. Seven grade I patients received the subtemporal middle cranial fossa approach (SMCF) combined with the canal wall up mastoidectomy and tympanoplasty (CWUT). Nine grade II patients underwent SMCF combined with subtotal petrosectomy (SPTR), and four grade II patients underwent SMCF combined with CWUT. Seven grade III patients received SMCF combined with SPTR and dura mater reconstruction, and four grade IV patients underwent infratemporal fossa approach type B. Gross total resection was achieved in all patients, and the median follow-up time was 30.1 months (range, 4–96 months). Three patients (one grade II, one grade III, and one grade IV) had recurrence during follow-up, and the patient with grade III tumor had two recurrences.

Conclusions

Gross total resection is the first-line treatment for patients with D-TGCT of the temporal bone. This novel grading system enables surgeons to select optimal surgical strategy. Long-term follow-up is mandatory postoperatively.

Level of Evidence

4 Laryngoscope, 2021

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Concise Communication: Kynurenine inhibits melanogenesis in human melanocyte‐keratinocyte co‐cultures, and in a reconstructed 3D skin model

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Abstract

Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co-cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already know inhibitory effect promoted by IFN-γ. Since increased KYN production depends on the IFN-γ-inducible enzyme indoleamine-2,3-dioxygenase (IDO), we propose that part of the effect of IFN-γ on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN, and downstream product s along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer.

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Combination of radiation therapy-immunotherapy for head and neck cancers: Promises kept?

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Cancer Radiother. 2021 Oct 25:S1278-3218(21)00252-3. doi: 10.1016/j.canrad.2021.08.018. Online ahead of print.

ABSTRACT

Chemoradiotherapy with concurrent cisplatin has been the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC) for over 20 years. Recently, immunotherapy, a new therapeutic class, has emerged for patients with recurrent or metastatic HNSCC and has significantly extended their survival. Will it bring the same benefit to patients with localized tumors? There is a strong rationale for combining radiation therapy and checkpoint inhibitors for HNSCC. Indeed, radiation therapy can have both immunostimulatory and immunomodulatory effects. This is what explains the famous abscopal effect. The aim of this review is to present the data available on the combination of radiation therapy and immunotherapy for HNSCC.

PMID:34711485 | DOI:10.1016/j.canrad.2021.08.018

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Differentiated Thyroid Carcinoma: Distant Metastasis as an Unusual Sole Initial Manifestation

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Turk Arch Otorhinolaryngol. 2021 Sep;59(3):188-192. doi: 10.4274/tao.2021.2021-2-5. Epub 2021 Oct 15.

ABSTRACT

OBJECTIVE: The objective of this study was to identify the characteristic features of patients with distant metastasis as the only manifestation of well-differentiated thyroid cancers and to analyze the treatment outcomes.

METHODS: A retrospective review of all patients with well-differentiated thyroid cancers and distant metastasis as the sole initial presentation w as carried out. Data regarding age, gender, tumor histology, site, symptoms, and treatment outcomes were collected.

RESULTS: There were 10 patients who presented with distant metastasis as the only presentation. The mean age was 56.1 years. Eight (80%) patients had osseous metastasis, one (10%) had pulmonary and one (10%) had both. Follicular thyroid carcinoma was more common and seen in six (60%) patients. Seven (77.8%) out of nine patients had demised within five years of initial presentation.

CONCLUSION: Distant metastases without a neck lump as the initial presentation of well-differentiated thyroid cancers are extremely rare. No specific guidelines are available to manage such patients due to lack of relevant data in the literature.

PMID:34713003 | PMC:PMC8527540 | DOI:10.4274/tao.2021.2021-2-5

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Subglottic cysts in preterm infants: superficially located cysts versus deeply buried cysts in the mucosa

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Eur Arch Otorhinolaryngol. 2021 Oct 29. doi: 10.1007/s00405-021-07142-4. Online ahead of print.

ABSTRACT

PURPOSE: To analyze the reason for the diversity of the clinical course of subglottic cysts and discuss their pre- and coexistence with subglottic stenosis.

METHODS: The medical records of patients who were treated for subglottic cysts between 2003 and 2020 were retrospectively reviewed and direct laryngoscopy videos were analyzed to assess the healing patterns of their disease.

RESULTS: Of the 15 patients, 10 had a history of intubation in the neonatal period. In 11 patients, the cysts were transparent and well defined, and no recurrence of subglottic cysts occurred after the initial surgery. In four patients, the cysts were located deep in the mucosa and did not have the typical appearance of a cyst, but rather of a stenotic segment; all of them had a history of intubation and three of them required laryngotracheal rec onstruction.

CONCLUSION: Transparent, thin-walled superficial subglottic cysts with healthy surrounding mucosa can easily be treated with endoscopic marsupialization; however, the treatment of deep subglottic cysts can be challenging. The coexistence of subglottic cysts and subglottic stenosis is not rare. We point out the need for considering the possibility of a missed deep submucosal cyst in a seemingly refractory case of pediatric subglottic stenosis with atypical endoscopic findings and with a background history of prior intubation.

PMID:34713339 | DOI:10.1007/s00405-021-07142-4

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The association between obstructive sleep apnea and stroke in sickle-cell disease children

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Eur Arch Otorhinolaryngol. 2021 Oct 29. doi: 10.1007/s00405-021-07125-5. Online ahead of print.

ABSTRACT

INTRODUCTION: The prevalence of stroke in SCD patients was reported to be around 4%; however, the pediatric category was among the higher risk group for stroke compared to young and middle age adults. Furthermore, the risk of OSA increases in SCD children. The objective of this study is to calculate the prevalence of stroke in children with SCD with and without obstructive sleep apnea.

METHOD: This is a cross-sectional study held at two major tertiary hospitals in Jeddah, Saudi Arabia. Inclusion criteria included patients aged between 2 and 18 at the time of enrollment with confirmed SCD. The primary outcome of the study was at least one documented episode of stroke over the last 3 years. OSA was assessed using PSQ.

RESULTS: A total of 150 children with SCD were included in the study. The mean age was 9.6 (±4.3). Most o f the sample (85.3%) were sickle-cell anemia with HbSS. Children who were positive for OSA were at higher odds of having a stroke [OR 2.97; 95% CI 1.13-7.75 (P = 0.02)]. The relationship between OSA and stroke was not significant in the multivariant analysis.

CONCLUSION: Patients who had OSA had a higher prevalence of stroke compared to non-OSA patients by 16% with almost three times higher odds. The difference was statistically significant in bivariant but not multivariant analysis. The rate of hospitalization, emergency visit, and blood transfusion were not affected by OSA status. Screening for OSA in high-risk patients such as SCD children and early management could prevent the risk of SCD complications.

PMID:34713338 | DOI:10.1007/s00405-021-07125-5

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