Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms-A Systematic Review.

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

Comparison of Ultrasound Versus Ultrasound With Nerve Stimulation-Guided Obturator Nerve Block to Prevent Adductor Spasm in Patients Undergoing Transurethral Resection of Bladder Tumor: A Randomized Controlled Study.

Background This study aimed to compare ultrasound versus ultrasound with nerve stimulation-guided obturator nerve block (ONB) for the prevention of adductor spasm in patients undergoing transurethral resection of bladder tumor (TURBT). Methodology This randomized controlled study included 240 adult patients in the age group of 30 to 70 years undergoing TURBT for lateral and posterolateral wall bladder tumors who fulfilled the American Society of Anesthesiologists grade I and II criteria. The patients were divided into two groups: group U (n = 120) included patients who underwent ONB using an ultrasound-guided technique and group UN (n = 120) included patients who underwent ONB using ultrasound with the nerve stimulation technique. Block performance time, adductor jerks/spasms, adductor muscle power, and patient and surgeon satisfaction were compared. A P-value <0.05 was considered statistically significant. Results The mean block performance time in group U was significantly less (4.4 ± 0.82 minutes) than in group UN (6.55 ± 0.37 minutes). Compared to group U, group UN had significantly fewer adductor jerks/spasms during the surgery (7.76% vs. 20.35%, p = 0.006), significantly more surgeon satisfaction (92.24% vs. 79.65%, p = 0.006), significantly more patient satisfaction (92.24% vs. 79.65%, p = 0.006), and comparable complications (excessive bleeding and minor bladder injury) and adductor muscle power after the block (p > 0.05). Conclusions ONB using the nerve stimulation technique under ultrasound guidance has a longer mean block performance time, a higher success rate, and higher surgeon satisfaction than ONB under ultrasound guidance only.

Efficacy and Safety of Obturator Nerve Block in Transurethral Resection of Bladder Tumors: A Comprehensive Review.

Transurethral resection of bladder tumors (TURBT) is a pivotal procedure in the management of bladder cancer, essential for both diagnosis and treatment. Effective anesthesia is crucial in TURBT to ensure a stable and pain-free operative field, facilitate precise tumor resection, and minimize complications such as the obturator reflex, which can lead to involuntary leg movement and bladder injury. The obturator nerve block (ONB) is a regional anesthesia technique designed to prevent the obturator reflex by blocking the obturator nerve, which innervates the adductor muscles of the thigh. This comprehensive review evaluates the efficacy and safety of ONB in TURBT. It begins by discussing the anatomical and physiological aspects of the obturator nerve, followed by a detailed examination of various ONB techniques, including ultrasound-guided and landmark-based methods. The review assesses the impact of ONB on pain management, reduction of adductor muscle spasms, and overall improvement in surgical conditions and patient satisfaction. Additionally, it explores the incidence and types of complications associated with ONB, such as hematoma, nerve injury, and local anesthetic systemic toxicity (LAST). It compares ONB with other anesthesia techniques used in TURBT, such as general, spinal, and epidural anesthesia. A critical analysis of key clinical studies and meta-analyses is presented to provide a comprehensive understanding of the current evidence on ONB efficacy and safety. Future directions and innovations in ONB techniques, including advances in imaging and nerve localization, are also discussed. Practical recommendations for implementing ONB in clinical practice, including guidelines for clinician training and patient selection criteria, are provided. This review aims to inform clinicians about the benefits and risks of ONB in TURBT, guide clinical practice, and identify areas for future research to optimize anesthesia management in bladder cancer surgery.

The impact of running versus interrupted anastomosis on ureterointestinal stricture rate after radical cystectomy.

PURPOSE: Benign ureterointestinal anastomotic stricture is not uncommon after radical cystectomy and urinary diversion. We studied the impact of the running vs the interrupted technique on the ureterointestinal anastomotic stricture rate. MATERIALS AND METHODS: From July 2007 to December 2008 interrupted end-to-side anastomoses were created and from January 2009 to July 2010 running anastomoses were created. The primary study end point was time to ureterointestinal anastomotic stricture. RESULTS: Of 266 consecutive patients 258 were alive 30 days after radical cystectomy, including 149 and 109 with an interrupted and a running anastomosis, respectively. The groups did not differ in age, gender, body mass index, age adjusted Charlson comorbidity index, receipt of chemotherapy or radiation, blood loss, operative time, diversion type or postoperative pathological findings. The stricture rate per ureter was 8.5% (25 of 293) and 12.7% (27 of 213) in the interrupted and running groups, respectively (p = 0.14). Univariate analysis suggested that postoperative urinary tract infection (HR 2.1, 95% CI 1.1-4.1, p = 0.04) and Clavien grade 3 or greater complications (HR 2.6, 95% CI 1.4-4.9, p <0.01) were associated with ureterointestinal anastomotic stricture. On multivariate analysis postoperative urinary tract infection (HR 2.4, 95% CI 1.2-5.1, p = 0.02) and running technique (HR 1.9, 95% CI 1.0-3.7, p = 0.05) were associated with ureterointestinal anastomotic stricture. Median time to stricture and followup was 289 (IQR 120-352) and 351 days (IQR 132-719) in the running cohort vs 213 (IQR 123-417) and 497 days (IQR 174-1,289) in the interrupted cohort, respectively. Of the 52 strictures 33 (63%) developed within 1 year. Kaplan-Meier analysis controlling for differential followup showed a trend toward higher freedom from stricture for the interrupted ureterointestinal anastomosis (p = 0.06). CONCLUSIONS: A running anastomosis and postoperative urinary tract infection may be associated with ureterointestinal anastomotic stricture. Larger series with multiple surgeons are needed to confirm these findings.

Sox2 and ßIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas.

Poorly differentiated sinonasal carcinomas (PDCs) are tumors that have a poor prognosis despite advances in classical treatment. Predictive and prognostic markers and new personalized treatments could improve the oncological outcomes of patients. In this study, we analyzed SOX2 and ßIII-tubulin as biomarkers that could have prognostic and therapeutic impacts on these tumors. The cohort included 57 cases of PDCs: 36 sinonasal undifferentiated carcinoma (SNUC) cases, 13 olfactory neuroblastoma (ONB) cases, and 8 sinonasal neuroendocrine carcinoma (SNEC) cases. Clinical follow-up data were available for 26 of these cases. Sox2 expression was detected using immunohistochemistry in 6 (75%) SNEC cases, 19 (53%) SNUC cases, and 6 (46%) ONB cases. The absence of Sox2 staining correlated with a higher rate of recurrence (p = 0.015), especially distant recurrence. The majority of cases showed ßIII-tubulin expression, with strong positivity in 85%, 75%, and 64% of SNEC, ONB, and SNUC cases, respectively. Tumors with stronger ßIII-tubulin expression demonstrated longer disease-free survival than those with no expression or low expression (p = 0.049). Sox2 and ßIII-tubulin expression is common in poorly differentiated sinonasal tumors and has prognostic and therapeutic utility.

Dramatic response to targeted therapy in an aggressive olfactory neuroblastoma: illustrative case.

BACKGROUND: Olfactory neuroblastomas are rare sinonasal tumors that arise from the olfactory epithelium. The authors presented a case of an olfactory neuroblastoma with extensive cranial invasion that demonstrated dramatic response to sorafenib, a tyrosine kinase inhibitor. OBSERVATIONS: A 54-year-old man with history of prostate cancer and melanoma presented with left-sided proptosis and was found to have a 6.5-cm Kadish stage D olfactory neuroblastoma with cranial invasion that was refractory to chemotherapy and everolimus. However, it demonstrated dramatic response to sorafenib, causing extensive skull base defects that prompted operative repair. Genomic analysis of the tumor revealed mutations in TSC1 and SUFU. The patient developed disease progression with liver metastases 35 months after starting sorafenib, prompting a change to lenvatinib. He experienced progression of his olfactory neuroblastoma 10 months following this change and died in hospice 1 month later. LESSONS: The authors reviewed the clinical presentation and management of a large olfactory neuroblastoma with dramatic response to sorafenib. They highlighted prior uses of targeted therapy in the management of refractory olfactory neuroblastoma within the context of current standard treatment regimens. Targeted therapies may play a vital role in the management of refractory olfactory neuroblastoma.

Within subject rise in serum TNFα to IL-10 ratio is associated with poorer attention, decision-making and working memory in jockeys.

Jockeys work in high-risk environments that rely heavily on attention- and decision-making to perform well and safely. Workplace stress literature has often overlooked the impact of stress on cognition, and designs that include physiological measures are rare. This study assessed the prospective concurrent relationships between workplace stress, depression symptoms and low-grade inflammation with cognitive performance among professional jockeys. Professional jockeys (N = 35, Mage = 32.29) provided information on workplace stress and depression symptoms, with serum levels of inflammatory cytokines (IL-6, IL-10, TNFα) and cytokine balance (IL-6: IL-10, TNFα: IL-10) quantified with SIMOA, and cognitive performance with CogSport computer-based testing battery. These measures were repeated after a twelve-month interval. Increased workplace stress between testing intervals was associated to an increased cytokine imbalance (ß = 0.447, p = .015) after controlling for age and gender. Increases in cytokine imbalance occurred in unison with decreases in attention (ß = 0.516, p = .002), decision-making (ß = 0.452, p = .009) and working memory (ß = 0.492, p = .004). These preliminary findings suggest the underlying mechanisms linking workplace stress and reduced cognitive performance may be influenced by measures of low-grade inflammation and specifically a cytokine imbalance. Our findings suggest a measure of cytokine balance may explain the heterogenous findings in previous studies that have focussed solely on the association of workplace stress with pro-inflammatory cytokines. Future work is needed however, to provide a broader evidence-base for our claims to better inform designs to intervene in the higher workplace stress-poorer cognition relationship.

Layered Niobium Oxide Hydrate Anode with Excellent Performance for Lithium-Ion Batteries.

Benefiting from the advantages of cost-effectiveness and sustainability, lithium-ion batteries (LIBs) are recognized as a next-generation energy technology with great development potential. Herein, niobium oxide hydrate (H3ONb3O8) synthesized by a facile and inexpensive solvothermal method is proposed as the anode of LIBs. It is a layered two-dimensional material composed of negatively charged two-dimensional lamellae and positively charged interlayer hydronium ions. The former consist of NbO6 octahedral units connected by bridging oxygen. Because of the mutual effect of hydronium ions and niobium oxide quantum dots, niobium oxide hydrate exhibits excellent electrochemical activity when used as an anode material. This compound is first applied to lithium-ion batteries, obtaining a high specific capacity (1232 mAh g-1) at 100 mA g-1 and maintaining an outstanding performance after 200 cycles. Therefore, this work not only proposes a simple preparation method of niobium oxide hydrate but also expands the variety of high-performance anode materials.

Comparison of a Hybrid IMRT/VMAT technique with non-coplanar VMAT and non-coplanar IMRT for unresectable olfactory neuroblastoma using the RayStation treatment planning system-EUD, NTCP and planning study.

The purpose of this study was to compare hybrid intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (Hybrid IMRT/VMAT), with non-coplanar (nc) IMRT and nc-VMAT treatment plans for unresectable olfactory neuroblastoma (ONB). Hybrid IMRT/VMAT, nc-IMRT and nc-VMAT plans were optimized for 12 patients with modified Kadish C stage ONB. Dose prescription was 65 Gy in 26 fractions. Dose-volume histogram parameters, conformation number (CN), homogeneity index (HI), integral dose and monitor units (MUs) delivered per fraction were assessed. Equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) based on the EUD model (NTCPLogit) and the Lyman-Kutcher-Burman model (NTCPLKB) were also evaluated. We found that the Hybrid IMRT/VMAT plan significantly improved the CN for clinical target volume (CTV) and planning treatment volume (PTV) compared with the nc-VMAT plan. In general, sparing of organs at risk (OARs) is similar with the three techniques, although the Hybrid IMRT/VMAT plan resulted in a significantly reduced Dmax to contralateral (C/L) optic nerve compared with the nc-IMRT plan. The Hybrid IMRT/VMAT plan significantly reduce EUD to the ipsilateral (I/L) and C/L optic nerve in comparison with the nc-IMRT plan and nc-VMAT plan, but the difference in NTCP between the three technique was <1%. We concluded that the Hybrid IMRT/VMAT technique can offer improvement in terms of target conformity and EUD for optic nerves, while achieving equal or better OAR sparing compared with nc-IMRT and nc-VMAT, and can be a viable radiation technique for treating unresectable ONB. However, the clinical benefit of these small differences in dosimetric data, EUD and NTCP of optic nerves may be minimal.

Intensity-modulated particle beam radiation therapy in the management of olfactory neuroblastoma.

BACKGROUND: To report the clinical experience and short-term efficacy in the management of olfactory neuroblastoma (ONB). METHODS: We performed a retrospective analysis of 12 ONB patients treated with particle beam radiation therapy (PBRT) between 12/2015 and 5/2019 at the Shanghai Proton and Heavy Ion Center. Four (33.3%) patients presented with Kadish B ONB, and 8 (66.7%) presented with Kadish C or D disease. Eleven patients received proton radiotherapy (PRT) followed by a carbon ion radiotherapy (CIRT) boost, one patient received CIRT only. The 2-year survival rates were calculated using the Kaplan-Meier method. Acute and late adverse events were summarized and scored according to the CTCAE (version 4.03). RESULTS: With a median follow-up of 17.5 (range, 2.53-49.9) months, all patients but 1 were alive. Eight patients were alive without evidence of disease, and 2 additional patients achieved partial response and remained alive with residual disease. One patient died of toxicity associated with salvage chemotherapy for distant metastasis and local failure. Another patient developed distant metastasis only and was alive at the time of the last follow-up. The 2-year OS, PFS, LRPFS, and DMFS rates were 83.3%, 75.8%, 87.5%, and 79.5%, respectively. No acute or late toxicities of ≥ grade 3 was observed. CONCLUSIONS: Intensity modulated PBRT of ONB is well tolerated. While longer follow-up is needed, early outcomes suggested that PBRT is safe and effective for the treatment of ONB with minimal adverse events.

Endonasal endoscopic resection of olfactory neuroblastoma: an 11-year experience.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal cavity. Surgery has been and remains a mainstay of treatment for patients with this tumor. Open craniofacial resections have been the treatment of choice for many decades. More recently, experience has been growing with endoscopic approaches in the management of patients with ONB. The object of this study is to report the authors' experience over the past 11 years with ONB patients treated with purely endonasal endoscopic techniques. METHODS: The authors performed a retrospective chart review of 20 consecutive patients with ONB who underwent a completely endonasal endoscopic approach for an oncological tumor resection at their institution between January 2006 and January 2017. Patient demographics, tumor stage, pathological grade, frozen section analysis, permanent margin assessment, perioperative complications, postoperative therapy, length of follow-up, and outcomes at last follow-up were collected and analyzed. RESULTS: Eighteen patients presented with newly diagnosed disease, with a modified Kadish stage of A in 2 cases, B in 3, C in 11, and D in 2. Two patients presented with recurrent tumors. An average of 25.3 specimens per patient were examined by frozen section analysis. Although analysis of intraoperative frozen section margins was negative in all but 1 case, microscopic foci of tumor were found in 7 cases (35%) on permanent histopathological analysis. Perioperative complications occurred in 7 patients (35%) including 1 patient who developed a cerebrospinal fluid leak; there were no episodes of meningitis. All but 1 patient received postoperative radiotherapy, and 5 patients received postoperative chemotherapy. With a mean follow-up of over 5 years, 19 patients were alive and 1 patient died from an unrelated cause. There were 2 cases of tumor recurrence. The 5-year overall, disease-specific, and recurrence-free survival rates were 92.9%, 100%, and 92.9%, respectively. CONCLUSIONS: The current results provide additional evidence for the continued use of endoscopic procedures in the management of this malignancy.

Treatment time, ease of use and cost associated with use of Equashield™, PhaSeal® , or no closed system transfer device for administration of cancer chemotherapy to a dog model.

This prospective experimental simulation study evaluated the efficiency, ease of use (EOU) and cost of administering chemotherapy with two closed system transfer devices (CSTD, Equashield™ and PhaSeal® ) and no CSTD. Forty-six veterinary technicians (VT) working in oncology specialty practices were timed during chemotherapy administration simulated with water and a model canine limb 10 times with each system and with no CSTD. EOU and likelihood of recommending each system were rated by VT using visual analog scales. Costs were obtained from veterinary distributors. Administration was fastest with Equashield™ (P = 0.0003), but the difference was not enough to affect case flow. Equashield™ was easier to use than PhaSeal® or no CSTD (P = 0.002), however VT recommended both CSTD more strongly than no CSTD (P < 0.0001). Equashield™ cost less than PhaSeal® but was sold only in bulk quantities. CSTD did not decrease efficiency in administering chemotherapy and were readily accepted by VT.

Validation of the Arabic version of the Functional Assessment of Cancer Therapy-Bladder questionnaire in Egyptian patients with bladder cancer.

OBJECTIVES: To validate the Arabic version of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) questionnaire in Egyptian patients who underwent radical cystectomy (RC) and orthotopic neobladder (ONB) construction. PATIENTS SUBJECTS AND METHODS: The English version of the FACT-Bl was translated into the Arabic language using multi-step process by two urologist and two independent translators. The Arabic version was validated by inviting 90 patients who underwent RC and ONB and 72 normal individuals to complete the questionnaire. The reliability of the questionnaire was tested for internal consistency using the Cronbach's α test. Inter-domain association was tested by Spearman's correlation coefficient. The discrimination validity was measured by comparing the scores in RC patients and in normal individuals using the Mann-Whitney U-test and independent sample t-test. RESULTS: Internal consistency was high for all domains. There was high correlation between all domains. This high internal consistency and good correlation was maintained when assessment included patients with <7.5 and those with ≥7.5 years follow-up. Discrimination validation was confirmed by the statistically significant lower scores of all domains in the studied patients in comparison to the controls. CONCLUSION: The Arabic version of the FACT-Bl is a reliable and validated instrument that can be used to evaluate health-related quality of life in patients after RC and ONB.