Oncolymphology: Immune Interactions and Cancer.

The proposed term "oncolymphology" encompasses the intimate relationship between cancer growth and the immune responses.

Validation of a three-dimensionally printed simulator for training in endoscopic sinonasal surgery.

BACKGROUND: The ability to incorporate different materials in the construction of 3-D printed models has resulted in the ability to mimic a variety of anatomical structures such as cartilage, mucosa and bone. The aim of this study was to evaluate the face and content validities of a model as a training tool for endoscopic sinus surgery. METHODS: Twenty-six delegates and ten teaching faculty members were invited to complete a post-hoc questionnaire survey. The survey consisted of a 22-question 5-point Likert scale to assess the model's realism (face validity) and its effectiveness as a training tool (content validity). RESULTS: Over 80% of the delegates agreed or strongly agreed that the appearance of anatomical structures within the model was realistic and mimicked actual sinus anatomy. In addition, a similar proportion agreed or strongly agreed that the application of instruments on the composite materials of the model realistically mimicked bone. All faculty agreed that the model was useful to develop hand-eye coordination and was a useful training tool for endoscopic sinus surgery. Overall, the sinus model received high scores regarding its use for training surgeons, especially to develop camera and instrument handling skills. CONCLUSION: The results of this study suggest that otolaryngology doctors in their early or intermediate stage of training would benefit most from a clinical-based modular programme. The model requires further development in areas such as the realism of mucosa, incorporation of sinonasal pathology and having more complex anatomy to be useful for the training of more advanced surgeons.

Review of management practices of sinogenic intracranial abscesses in children.

OBJECTIVE: This study aimed to evaluate the management practices and outcomes in children with sinogenic intracranial suppuration. METHOD: This was a retrospective cohort study in a single paediatric tertiary unit that included patients younger than 18 years with radiologically confirmed intracranial abscess, including subdural empyema and epidural or intraparenchymal abscess secondary to sinusitis. Main outcomes studied were rate of return to the operating theatre, length of hospital stay, death in less than 90 days and neurological disability at 6 months. RESULTS: A cohort of 39 consecutive patients presenting between 2000 and 2020 were eligible for inclusion. Subdural empyema was the most common intracranial complication followed by extradural abscess and intraparenchymal abscess. Mean length of hospital stay was 42 days. Sixteen patients were managed with combined ENT and neurosurgical interventions, 15 patients underwent ENT procedures alone and 4 patients had only neurosurgical drainage. Four patients initially underwent non-operative management. The rates of return to the operating theatre, neurological deficits and 90-day mortality were 19, 9 and 3, respectively, and were comparable across the 4 treatment arms. In the univariate logistic regression, only the size of an intracranial abscess was found be associated with an increased likelihood of return to the operating theatre, whereas combined ENT and neurosurgical intervention did not result in improved outcomes. CONCLUSION: Sinogenic intracranial abscesses are associated with significant morbidity and mortality. The size of an intracranial abscess has a strong association with a need for a revision surgery.

Neurological pain relief interventional radiology procedures.

Neurological interventions have taken on a significant role in interventional radiology (IR) practice. Indications fall under three main categories: (1) intraprocedural pain management, (2) cancer pain palliation, and (3) chronic non-cancer pain control. Short-term regional anaesthesia can be achieved with local anaesthetics, while longer-term pain control can be attained with radiofrequency neuromodulation (pulsed or otherwise) or thermal/chemical neurolysis. This review article summarises the therapeutic options, applications, and techniques of commonly used peripheral nerve and plexus interventions in IR.

Octyl cyanoacrylate skin adhesive with or without subcuticular suture for skin closure after implantable venous port placement for oncology patients: a propensity-score matching analysis.

AIM: To compare peri-operative outcomes of skin closure with octyl cyanoacrylate (OCA) skin adhesive (Dermabond) with or without subcuticular sutures after deep dermal suturing for implantable venous port placement closure. MATERIALS AND METHODS: Seven hundred and ninety-two single-lumen implantable venous port insertions for chemotherapy were reviewed from September 2019 to March 2021 in a retrospective single-centre study. Propensity-score matching by a 1:1 nearest neighbour algorithm was conducted to control for confounding baseline differences. Distances were determined by logistic regression. Propensity-score matching was performed based on the following variables: age at procedure, gender, race, operator's seniority, use of anchoring polypropylene suture (PROLENE), port model, and volume of intra-operative local analgesia. The primary outcome was wound dehiscence at the first follow-up (∼1 week). RESULTS: The 792 port insertions were conducted in 302 males (38.1%), median age 63 years (IQR: 54-69). Of the 656 wounds closed with subcuticular sutures and skin adhesive, 136 were matched in a 1:1 fashion against procedures closed without a subcuticular suture. No significant differences were demonstrated in pain scores, bleeding, swelling, bruising, fever, wound dehiscence, and discharge at postoperative day 1 (POD1) and at first follow-up between the groups (all p>0.05). Of note, no significant differences in wound dehiscence at first follow-up was found in both unmatched (p=0.133) and matched cohorts (McNemar-Bowker's χ2 = 1.167, p=0.761). CONCLUSION: These findings suggest that the omission of subcuticular sutures during implantable venous port closure may not compromise peri-operative outcomes when OCA skin adhesives were used.

Does endoscopic balloon dilatation improve intranasal drug delivery to the olfactory cleft? A pre-clinical cadaver feasibility study.

BACKGROUND: Although systemic steroids have been shown to improve olfactory function, topical steroids have not demonstrated the same efficacy. This could a result of limited drug delivery to the narrow, superiorly placed olfactory cleft. This study aimed to examine the penetration of intranasal drugs to the olfactory cleft following endonasal balloon dilatation. METHODS: Balloon dilatation was performed in 12 thawed, fresh-frozen cadaver specimens. In the Mygind position, nasal drops mixed with blue food dye were administered into the nostril before and after the dilatation procedure. Endoscopic videos were recorded to assess dye staining of the olfactory cleft and osteo-meatal complex using a 4-point Likert scale. RESULTS: Prior to balloon dilatation, the mean penetration of nasal drops into the olfactory cleft was 1.34, which improved significantly (p < 0.05) to 2.66 following the procedure. There was no change in dye penetration into the osteo-meatal complex after balloon dilatation. CONCLUSION: The results of this exploratory study suggest that balloon dilatation may improve the delivery of nasal drops to the olfactory cleft area. The clinical applicability and impact on olfactory function will require further assessment.

Outcome of neoadjuvant treatment for pancreatic cancer in elderly patients: comparative, observational cohort study.

BACKGROUND: Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. METHODS: This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70-74, 75 or more years) and respective treatment outcomes were compared. RESULTS: The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70-74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70-74 years, and 12 of 34 aged 75 years or more; P < 0.001). Resectability was similar among the three groups (60.0, 58.3, and 55.9 per cent respectively; P = 0.919). Trends towards shorter survival were observed in the elderly (median overall survival time 23.6, 18.0, and 17.6 months for patients aged less than 70, 70-74, and 75 or more years respectively; P = 0.090). After adjusting for co-variables, age was not a significant predictive factor. CONCLUSION: The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.

In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids.

A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.

Pre-Operative Embolisation of Musculoskeletal Tumours - A Single Centre Experience.

INTRODUCTION: The management of musculoskeletal tumours is complex and requires a multi-disciplinary approach. Preoperative embolisation can be often employed to reduce intra-operative blood loss and complication rates from surgery. We report our experience with the safety, technical success and efficacy of pre-operative embolisation in musculoskeletal tumours. MATERIALS AND METHODS: Thirteen consecutive patients who underwent pre-operative embolisation of a musculoskeletal tumour followed by surgical intervention at our institution from May 2012 to January 2016 were enrolled into the study. Patient demographics, tumour characteristics, embolisation techniques and type of surgery were recorded. Technical success of embolisation, amount of blood loss during surgery and transfusion requirements were estimated. RESULTS: There were five female and eight male patients who underwent pre-operative embolisation during the study period. The age ranged between 16 to 68 years, and the median age was 54. Technical success was achieved in all patients. Mean intra-operative blood loss was 1403ml, with a range of 150ml to 6900ml. Eight patients (62%) required intra-operative blood products of packed red blood cells and fresh frozen plasma. No major complications occurred during embolisation. CONCLUSION: Pre-operative trans-arterial embolisation is feasible and safe for a variety of large and hypervascular musculoskeletal tumours. Our small series suggests that preoperative embolisation could contribute to the reduction of the intra-operative and post-operative blood product transfusion. It should be considered as a pre-operative adjunct for major tumour resections with a high risk of bleeding. The use of the haemoglobin gap complemented the assessment of perioperative blood loss.

Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases.

Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.

A risk prediction model for the development of subsequent primary melanoma in a population-based cohort.

BACKGROUND: Guidelines for follow-up of patients with melanoma are based on limited evidence. OBJECTIVES: To guide skin surveillance, we developed a risk prediction model for subsequent primary melanomas, using demographic, phenotypical, histopathological, sun exposure and genomic risk factors. METHODS: Using Cox regression frailty models, we analysed data for 2613 primary melanomas from 1266 patients recruited to the population-based Genes, Environment and Melanoma study in New South Wales, Australia, with a median of 14 years' follow-up via the cancer registry. Discrimination and calibration were assessed. RESULTS: The median time to diagnosis of a subsequent primary melanoma decreased with each new primary melanoma. The final model included 12 risk factors. Harrell's C-statistic was 0·73 [95% confidence interval (CI) 0·68-0·77], 0·65 (95% CI 0·62-0·68) and 0·65 (95% CI 0·61-0·69) for predicting second, third and fourth primary melanomas, respectively. The risk of a subsequent primary melanoma was 4·75 times higher (95% CI 3·87-5·82) for the highest vs. the lowest quintile of the risk score. The mean absolute risk of a subsequent primary melanoma within 5 years was 8·0 ± SD 4.1% after the first primary melanoma, and 46·8 ± 15·0% after the second, but varied substantially by risk score. CONCLUSIONS: The risk of developing a subsequent primary melanoma varies considerably between individuals and is particularly high for those with two or more primary melanomas. The risk prediction model and its associated nomograms enable estimation of the absolute risk of subsequent primary melanoma, on the basis of on an individual's risk factors, and can be used to tailor surveillance intensity, communicate risk and provide patient education. What's already known about this topic? Current guidelines for the frequency and length of follow-up to detect new primary melanomas in patients with one or more previous primary melanomas are based on limited evidence. People with one or more primary melanomas have, on average, a higher risk of developing another primary invasive melanoma, compared with the general population, but an accurate way of estimating individual risk is needed. What does this study add? We provide a comprehensive risk prediction model for subsequent primary melanomas, using data from 1266 participants with melanoma (2613 primary melanomas), over a median 14 years' follow-up. The model includes 12 risk factors comprising demographic, phenotypical, histopathological and genomic factors, and sun exposure. It enables estimation of the absolute risk of subsequent primary melanomas, and can be used to tailor surveillance intensity, communicate individual risk and provide patient education.

Case series of testicular adrenal rest tumours in boys with congenital adrenal hyperplasia: A single centre experience.

Testicular adrenal rest tumours (TART) are aberrant adrenal tissue within the testes (1). Although benign, they can lead to obstruction of the seminiferous tubules and infertility in patients with congenital adrenal hyperplasia (CAH). We report six boys who developed TART, a complication of CAH. Diagnosis was confirmed by ultrasound and testicular vein sampling of elevated 17-hydroxyprogesterone (17-OHP) levels. Glucocorticoids dosages were increased 1½-2 folds to suppress size of the aberrant adrenal tissues. Despite reductions in 17-OHP, the lesions remained unchanged. Three patients had testis-sparing surgery to excise the TART and to preserve normal testicular tissues.

Assessing the ideal microwave duration for disinfection of sinus irrigation bottles-A quantitative study.

OBJECTIVES: Saline irrigation of the nasal cavity and paranasal sinuses has a recognised role in the management of chronic rhinosinusitis. However, bacterial recontamination of irrigation bottles through backflow from the sinonasal cavity is a concern in recurrent sinus cavity infections. While patients are encouraged to clean the irrigation bottles regularly, there remains significant concern that the use of contaminated bottles may perpetuate chronic rhinosinusitis. This study assesses the optimal microwave duration to achieve decontamination for each irrigation bottle component part (reservoir, tube and nozzle) using a standard, commercially available microwave. In addition, the irrigation fluid was also tested for contamination after each microwave cycle. STUDY DESIGN: Laboratory-based experimental study. PARTICIPANTS: No patients were involved in this study. MAIN OUTCOME MEASURES: The percentage in vitro decontamination of the bottles' components was determined following 30, 60, 90, 120, 150 seconds of microwave cycles. RESULTS: Complete decontamination of the bottles was not achieved at any of the tested microwave cycles. Levels of decontamination differed for the different bottle components, and the greatest degree of decontamination for all bottle components occurred at 90 seconds. Although higher levels of decontamination were observed at microwave durations exceeding 90 seconds, this was at the expense of thermal degradation and deformation of the reservoir plastic component of the irrigation bottle. Similarly, lowest contamination of irrigation fluid was observed at 120 seconds. CONCLUSIONS: This study highlights the importance of establishing precise decontamination procedures and recommends a microwave cycle of 90 seconds for optimal decontamination.

Sino-Nasal Outcome Test-22 quality-of-life patterns in patients presenting with nasal septal perforation.

OBJECTIVES: To assess the impact of nasal septal perforation (NSP) on quality of life. DESIGN: Retrospective cohort study. SETTING: Rhinology clinics from two hospitals in Liverpool, United Kingdom. PARTICIPANTS: Patients diagnosed with NSP. MAIN OUTCOME MEASURES: Patients (n = 26) diagnosed with NSP completed the Sino-Nasal Outcome Test-22 (SNOT-22). The collated data were compared with SNOT-22 scores from a cohort of healthy volunteers (n = 34) and a cohort of patients (n = 30) diagnosed with chronic rhinosinusitis (CRS). RESULTS: The mean total SNOT-22 score of NSP and CRS cohorts was higher than that observed in healthy volunteers. The mean total SNOT-22 score in the CRS cohort (57.2, standard deviation SD 10.3) was the higher than NSP (50.2, SD 23.5), although this difference did not achieve statistical significance. The mean score for the rhinologic-specific domains (rhinologic symptoms, extranasal rhinologic symptoms), ear/facial symptoms and psychological dysfunction domain was higher in the CRS cohort compared to NSP, although statistical significance was only observed in the extranasal rhinologic symptoms domain (11.2, SD 2.4 vs 6.4, SD 4.1). Conversely, the mean sleep dysfunction domain score for NSP (12.7, SD 7.5) was higher than CRS (10.0, SD 4.9, respectively) although this was not statistically significant. CONCLUSIONS: This study has assessed the clinimetric and psychometric properties of patients suffering from symptomatic NSP. Future reports should consider inclusion of SNOT-22 data but with the addition of perforation-specific symptoms (nasal crusting, epistaxis, whistling noise).

Management of asthma in adults in primary care.

Asthma is a chronic inflammatory disease of the airway which is often misdiagnosed and undertreated. Early diagnosis and vigilant asthma control are crucial to preventing permanent airway damage, improving quality of life and reducing healthcare burdens. The key approaches to asthma management should include patient empowerment through health education and self-management and, an effective patient-healthcare provider partnership.

Laparoscopic and open inguinal hernia repair: Patient reported outcomes in the elderly from a single centre - A prospective cohort study.

BACKGROUND: With those over 65 making up over 16% of the UK's population, surgeons are counselling increasing numbers of elderly patients for hernia repair. Data is currently lacking comparing different repair methods of inguinal hernias in the elderly population with regards to patient reported outcomes. AIM: To compare open and laparoscopic hernia repair in patients >65 years old and those <65 years old with respect to patient reported outcomes. METHOD: As part of a quality assurance process patients receive a telephone consultation day 2 post procedure. This includes an optional survey with questions to quantify pain, general feeling, nausea, dizziness, drowsiness, satisfaction and vomiting since the operation. Patients were then classified into age ≥ 65 years or <65 years and subclassified into totally extraperitoneal (TEP) or open inguinal hernia repair (IHR). RESULTS: Data is presented from patients treated between January 2009 and August 2016, totalling those included 1167 of 2522 (55.5%). Only five patients (4.42%) reported moderate pain; in the >65 TEP group this was significantly lower (10.2% open IHR <65; 6.7% TEP <65; 12.8% open IHR >65). Patient satisfaction with the surgery was satisfied or very satisfied in all patients in all groups. CONCLUSION: Time off work is not an absolute appropriate measure of return to premorbid status with respect to the elderly as a substantial number of >65 year olds have retired. We therefore present this interesting insight into patient perceptions following hernia repair by age group. Overall patients over 65 can expect the same high levels of satisfaction and low levels of pain following either technique for inguinal hernia repair as younger patients.

The BeSMART (Best Supportive Management for Adults Referred with Tonsillopharyngitis) multicentre observational study.

Introduction Tonsillopharyngitis is the most common ear, nose and throat emergency admission, with 80,000 episodes recorded in England in 2015-2016. Despite this, there is a paucity of evidence addressing the supportive management of tonsillopharyngitis in inpatients. The aim of this retrospective multicentre observational study was to consider the Best Supportive Management for Adults Referred with Tonsillopharyngitis (BeSMART) in the inpatient setting, and to establish any associations between practice and outcomes. Methods Seven hospitals in North West England and North East Scotland participated in the study. Overall, 236 adult patients admitted with tonsillopharyngitis were included. The main outcome measures were interval to return to soft diet, length of stay (LOS), pain scores and readmissions. Results Women were more likely to seek professional help before presenting to secondary care (p=0.04). Patients admitted at the weekend were more likely to have a shorter LOS (p=0.03). There was no relationship between day of admission and seniority or specialty of the doctor initially seen. Prescription of corticosteroid, analgesia and a higher initial intravenous fluid infusion rate were not related to a shorter LOS. Conclusions This study is the first to yield valuable insights into the inpatient management of tonsillopharyngitis. This work represents part of an ongoing project to establish the evidence for common medical interventions for sore throat. Patient and professional surveys as well as a prospective interventional study are planned for the future.