Multidisciplinary Management of Phyllodes Tumours and Breast Sarcoma: A Cross-sectional Survey of Clinical Practice across the UK and Ireland.

AIMS: Phyllodes tumours and breast sarcomas are uncommon tumours and their rarity poses significant challenges in diagnosis and management. This cross-sectional study was conducted to evaluate the multidisciplinary clinical practice for these tumours across the UK and Ireland, with the aim of identifying gaps in knowledge and providing direction for establishing national guidelines. MATERIALS AND METHODS: An international survey was adapted and circulated to breast and/or sarcoma surgeons and oncologists in the UK and Ireland through national organisations. Multidisciplinary team (MDT) responses were analysed anonymously. RESULTS: Twenty-eight MDTs participated in this study, predominately from high-volume units (85.5%). Although only 43% of the surveyed units were part of a trust that holds a sarcoma MDT, 68% of units managed malignant phyllodes and angiosarcoma, whereas 64.5% managed soft-tissue sarcoma of the breast. Across all subtypes, axillary surgery was recommended by 14-21% of the MDTs and the most recommended resection margins for breast surgery were 'no tumour on ink' in benign phyllodes (39%) and 10 mm in the remaining subtypes (25-29%). Immediate breast reconstruction was supported by 11-18% of MDTs for breast sarcoma subtypes, whereas 36% and 32% advocated this approach in benign and borderline phyllodes tumours, respectively. Adjuvant radiotherapy and chemotherapy were recommended by up to 29% and 11% of the MDTs, respectively. CONCLUSION: The results of this study demonstrate a wide variation in clinical practice across the surveyed MDTs. As only 28 MDTs participated in our study, with under-representation from low-volume units, our results might be an underestimation of the variability in practice across the UK and Ireland. This multi-institutional study sheds light on controversial aspects in the management of phyllodes tumours and breast sarcoma, identifies the need for national guidelines to inform best practice, and calls for the centralisation of the management of breast sarcoma within specialist centres.

Near total intrathoracic airway obstruction managed with a Tritube® and flow-controlled ventilation.

We describe the management of a case of near total airway obstruction in a 79-year-old man who presented with a 2-week history of increasing shortness of breath and stridor. Computed tomography imaging revealed a mid-tracheal mass of unknown aetiology with critical airway obstruction. We secured the patient's airway using a TriTube® (Ventinova, Eindhoven, the Netherlands). While this facilitated a secure airway past the lesion, various issues were encountered which complicated the safe conduct of anaesthesia. We conclude that while the TriTube and Evone® flow-controlled ventilation (Ventinova) are useful for critical airway obstruction, they can be problematic and thorough planning is essential.

Laryngectomy with a Tritube® and flow-controlled ventilation.

We describe the novel use of the TriTube® and Evone® ventilator (Ventinova, Eindhoven, Netherlands) to facilitate curative resection of a transglottic squamous cell carcinoma. A 43-year-old man presented with acute laryngeal and subglottic airway obstruction secondary to a stage 4 transglottic squamous cell carcinoma. The patient underwent magnetic resonance imaging followed by a diagnostic panendoscopy. It was decided that tumour resection was appropriate and a management plan was established by a multi disciplinary team. A total laryngectomy was performed. It was determined that failure of translaryngeal tracheal intubation could be rescued with emergency surgical front-of-neck airway. General anaesthesia was induced using a total intravenous anaesthesia technique, oxygenation was achieved with high-flow nasal oxygen and the airway was secured using the TriTube and flow-controlled ventilation was delivered throughout the procedure using the Evone ventilator. This avoided an awake or emergency tracheostomy, with the associated theoretical risk of tumour seeding, allowed for excellent gas exchange throughout and permitted the surgeons to maintain a closed system during much of the procedure, including during fashioning of the stoma. When traditional laryngectomy tubes are used, this process ordinarily involves multiple extubations and apnoeic periods. Furthermore, the small subglottic tube allowed intra-operative assessment of the extent of the subglottic tumour, facilitating curative en bloc resection.

Apnoeic ventilation for shared airway surgery during the COVID-19 pandemic.

This report describes the care provided to a 64-year-old woman presenting with airway obstruction following recovery from COVID-19 pneumonitis, prolonged tracheal intubation and tracheostomy weaning. Her initial admission was with COVID-19 pneumonitis during the first surge of cases in early 2020, and was complicated by multiple bilateral segmental pulmonary emboli, a 28-day stay in intensive care, 16 days of mechanical ventilation and finally, a tracheostomy with subsequent weaning of respiratory support and rehabilitation. On presentation, her symptoms of airway obstruction were because of significant granuloma of the posterior glottis and subglottis, as well as a mild lambdoid deformity at the site of her previous tracheostomy. The key learning points described relate to the use of apnoeic oxygenation during the COVID-19 pandemic, managing the shared airway, as well as the management of post-intubation laryngotracheal complications.

A multidisciplinary approach for managing the infraglottic difficult airway in the setting of the Coronavirus pandemic.

Management of a difficult airway caused by pathology below the glottis is high-risk and requires a shared approach to airway planning and surgical treatment. Access to the trachea requires a careful assessment of the airway since the end-point of laryngoscopy for infraglottic airway management is not visualization of the larynx for tube placement, but access to the laryngotracheal complex in cases where intubation may not be feasible or may preclude surgical access. This work provides a common framework for creating multidisciplinary shared-airway management plans and presents devices and strategies that have in recent years improved airway management safety in this difficult patient group and may prove useful in the setting of the novel Coronavirus Disease 2019 (COVID-19).

Circulating tumour cells as a biomarker for diagnosis and staging in pancreatic cancer.

BACKGROUND: Current diagnosis and staging of pancreatic ductal adenocarcinoma (PDAC) has important limitations and better biomarkers are needed to guide initial therapy. We investigated the performance of circulating tumour cells (CTCs) as an adjunctive biomarker at the time of disease presentation. METHODS: Venous blood (VB) was collected prospectively from 100 consecutive, pre-treatment patients with PDAC. Utilising the microfluidic NanoVelcro CTC chip, samples were evaluated for the presence and number of CTCs. KRAS mutation analysis was used to compare the CTCs with primary tumour tissue. CTC enumeration data was then evaluated as a diagnostic and staging biomarker in the setting of PDAC. RESULTS: We found 100% concordance for KRAS mutation subtype between primary tumour and CTCs in all five patients tested. Evaluation of CTCs as a diagnostic revealed the presence of CTCs in 54/72 patients with confirmed PDAC (sensitivity=75.0%, specificity=96.4%, area under the curve (AUROC)=0.867, 95% CI=0.798-0.935, and P<0.001). Furthermore, a cut-off of ⩾3 CTCs in 4 ml VB was able to discriminate between local/regional and metastatic disease (AUROC=0.885; 95% CI=0.800-0.969; and P<0.001). CONCLUSION: CTCs appear to function well as a biomarker for diagnosis and staging in PDAC.

Outcomes of adults with acute myelogenous leukemia in remission given 550 cGy of single-exposure total body irradiation, cyclophosphamide, and unrelated donor bone marrow transplants.

On the basis of observations from dog models and human studies, we hypothesized that a low-dose (550 cGy), single-exposure total body irradiation (TBI)-based regimen would result in improved survival when given to adult patients with acute myelogenous leukemia (AML) who were undergoing unrelated donor bone marrow transplantation in complete remission (CR). The regimen consisted of single exposure (550 cGy) of TBI given at a high dose rate (30 cGy/min) and cyclophosphamide. Graft-versus-host disease prophylaxis consisted of cyclosporine, methotrexate, and corticosteroids. Thirty-two consecutive adult patients (median age, 47 years) with AML in CR (15 in CR 1 and 17 in CR > or =2) were treated. Sixteen patients (50%) were alive and in remission at last follow-up (median, 2.2 years; range, 0.6-4.0 years). Kaplan-Meier estimates of overall and leukemia-free survival at 3 years were 55% +/- 14% (mean +/- SE) and 57% +/- 14% in CR 1 patients and were both 39% +/- 12% in CR > or =2 patients. Transplant-related mortality was 13% for patients in CR 1 and 41% for those in CR > or =2. Only 1 patient (3%) experienced fatal regimen-related organ toxicity, and only 1 had grade III or IV acute graft-versus-host disease. Graft failure was not observed. Relapse occurred in 22% of patients. This low-dose (550 cGy), single-exposure TBI-based regimen resulted in good survival and a low risk of fatal regimen-related organ toxicity in adult patients with AML who underwent unrelated donor bone marrow transplantation in CR.

The role of chemical engineering in pharmaceutical chemical process development.

The task of chemical process development in the pharmaceutical industry has grown into a multidisciplinary endeavor requiring years to complete. Increased competition in the pharmaceutical Additionally, the ever-tightening regulatory environment further compromises the business objective (ultimately, profits). This has required careful analysis of the activities within development. This work discusses the results of this analysis, which shows how a balance between minimal resource utilization and phased development achievements can be reached. The cycle of development, from inception to completion, is examined. Special emphasis is placed upon the role of chemical engineering and its appropriate deployment. Simple examples of the synergies that are possible between chemistry and chemical engineering are also given.

Bilharzial granuloma of the conus: case report.

Schistosomiasis of the central nervous system is uncommon. Schistosoma mansoni is the most common cause of a spinal cord lesion, although Schistosoma haematobium is sometimes responsible. The conus medullaris is the primary site for spinal lesion. The spinal lesion of schistosomiasis may be in the form of a mass lesion or acute necrotizing myelitis, or it may be silent and symptomless. Diagnosis of spinal cord schistosomiasis is commonly retrospective but may be suggested by laboratory and radiological studies. We were confronted with a case of bilharzial granuloma of the conus in a 7-year-old boy. This patient sought treatment for sphincteric disturbance. Myelography showed an intradural lesion in the area of the conus (opposite L1-L2). The mass proved pathologically to be S. haematobium granuloma. There was no previous history of bilharzial infestation. The neurological deficits improved markedly after surgery and antibilharzial treatment.

Evaluation of Klippel-Trenaunay syndrome with radionuclide total body angiography. A case report.

A 21-year-old Italian woman with extensive Klippel-Trenaunay syndrome (KTS) developed recurrent pulmonary embolism in spite of the insertion of a Greenfield filter in the inferior vena cava. Clinical and radiologic diagnostic tests failed to demonstrate the pathway of the emboli. Radionuclide venography and intravenous radionuclide total body arteriography were performed. These radionuclide procedures helped to evaluate the extent of KTS and to detect the route of the emboli. This is the first case of KTS studied with intravenous total body arteriography reported in the literature.

The interface between bone, soft tissue, and dental implants.

The normal healing responses of soft tissues and bone to injury, including the sequence of cellular activity, are presented. The nature of the attachment of the implant to the biological tissues may be either poorly differentiated fibrous tissue or direct anchorage in vital bone (preferred). Attachment by a highly differentiated periodontal ligament is presently not possible. The gingival seal has been found to be similar to that around the natural tooth. Commercially pure titanium is one of the best materials to use in terms of its biological compatibility with bone; polymers, carbons and controlled surface, i.e. active bioglasses, are also satisfactory. A porous low modulus coating is useful. Design of the implant and force transfer, as well as surgical treatment are among the important factors that determine how the interface will develop.

A combined histochemical-neurophysiological technique for investigating the extent of diffusion of intracerebrally injected drugs.

In order to 'dissect out' the function of a given region of the brain, the local application of a chemical transmitter probably parallels closely what is actually occurring biologically at the local site. This paper addresses itself to the problem of diffusion of drugs and describes the application of a modern device (the osmotic minipump) which produces a constant flow of minute quantities of the agent into the brain structure. Neurophysiological, behavioural, and histochemical investigations have been carried out in different species. Although the histochemical results of the minipump experiments indicate some spread, yet this seems to be at a concentration which would have no apparent pharmacological action. This was confirmed by our neurophysiological and behavioural studies and also by some recent reports in the literature.

Combined use of the chemitrode with osmotic minipumps for experimental brain research.

This paper describes a simple-to-build minipump-chemitrode assembly which can be used for long term electrophysiological, chemical and behavioural studies. This system consists of an osmotic minipump, a cannula and an array of nine electrodes which are connected to a miniature Winchester Socket. A detailed plan for construction of both the chemitrode and the minipump-chemitrode is given together with some suggestions for possible usages in brain research(such as kindling). The osmotic minipump consists of a collapsible reservoir of flexible, impermeable material, surrounded by a sealed layer containing an osmotic agent--all of which is contained by a semipermeable membrane. Imbibed water generates hydrostatic pressure on the flexible lining of the reservoir, gradually compressing it, producing a constant flow of its contents through the delivery portal.

Electrical versus cholinergic kindling.

The present investigation was designed to test the hypothesis that cholinergic neurones may constitute a critical element in the neuronal circuitory of kindling. Chemitrodes implanted in monkey and rabbit brain enabled both electrical and chemical stimulations of limbic structures. The results indicated that only few electrical kindling stimuli produce prolonged supersensitivity to intracerebrally injected physostigmine. A subsequent electrical stimulus continues the kindling progression. The cholinergic supersensitivity persists for a long time and is only suppressed by intramuscular injections of scopolamine. These findings fit best with the hypothesis that participation of muscarinic cholinergic receptors may be an important requirement of the kindling process. It appears likely that similar types of mechanisms are involved both in chemical and electrical kindling.