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1.
Clinical Osteology ; 26(2):98-102, 2021.
Article in Slovak | EMBASE | ID: covidwho-1820597

ABSTRACT

Heterotopic ossification is well-described, often complication after musculoskeletal trauma, surgery and neuro-trauma. We present a patient who developed heterotopic ossification of hip joints with bony ankylosis after prolonged artificial pulmonary ventilation because of pulmonary failure after H1N1 pneumonia. Atraumatic heterotopic ossification occurs in critically ill patients after mechanical ventilation, including patients with COVID-19 disease. We consider imobilization and artificial pulmonary ventilation as a possible causal factors of heterotopic ossification. Early diagnosis and implementation of potentional preventive and therapeutical tools, such as anti-inflammatory drugs and appropriate physiotherapy, are needed to decrease morbidity in patients with risk factors. The timing of surgical excision must be considered according to a risk of recurrence and irreversible joint damage.

2.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779446

ABSTRACT

Background: Genomic profiling assays for invasive breast cancer provide useful predictive and prognostic information and are performed most commonly on surgical resection specimens. Obtaining the molecular profile at the time of initial core needle biopsy is ideal because it could provide information that could significantly alter preoperative decision-making and avoid unnecessary treatments. In January 2020, the breast center began a 3 month pilot program that would reflexively send core biopsy material on all newly diagnosed patients for genomic testing using the MammaPrint (MPT) and BluePrint (BPT) assays regardless of receptor status. The goals were to determine feasibility and examine the impact to patient care. Methods: Breast core biopsy tissue was triaged by an attending pathologist as soon as slides were available. If invasive carcinoma with at least 3 mm in linear extent of tumor with 20% cellularity was identified, materials were immediately sent to Agendia for MPT/BPT testing even before ER/PR/HER2 testing was available to the pathologist. Clinicopathologic information, turn-around time (TAT) and adequacy data were tracked. The impact was discussed regularly at breast tumor board to determine if the results led to altered decision-making that could reduce unnecessary interventions and time to initial treatment. Results: 445 core biopsy specimens were sent for genomic testing. Of those 442, (97%) Syielded genomic results with an average TAT from biopsy to genomic result of 11 calendar days. MPT identified 233 (53%) cases that were low risk and 209 (47%) cases that were high risk. BPT showed that 60 (14%) cases were Basal, 18 (4%) cases were HER2, and 364 (82%) cases were Luminal. Further analysis of the Luminal subgroup demonstrated that 154 (42%) were Luminal A low risk, 78 (21%) were Luminal A Ultralow risk and 132 (36%) were Luminal B High Risk. Analysis by race demonstrated a significantly higher percentage of high risk tumors in African-American women including a higher percentage of basal cancers (26%) as compared to Caucasian women (10%). Of note, 51 patients in the pilot study had additional OncotypeDX (ODX) testing on subsequent surgical resection. There was fair correlation between the assays with the majority of the low risk MPT having low risk ODX scores (<=25) and the high risk MPT having high risk ODX scores (>25), though MPT identified more patients as being high risk. The COVID-19 pandemic altered plans to assess time to treat and treatment interventions as initially intended. However, the knowledge of genomic result enhanced the ability to triage patients, allowing those patients with low risk tumors to begin endocrine therapy and delay surgery. Use of preoperative hormone therapy was considered more often in place of neoadjuvant chemotherapy in patients with low genomic risk ER+/HER2-patients. Because of the continued feedback indicating positive impact, the pilot ultimately was extended to 11 months to allow time for formal implementation. Conclusions: Genomic testing using the MPT/BPT assay on core biopsy samples with at least 3 mm yields results 97% of the time with an average TAT of 11 days from biopsy date to result. The genomic information at the time of initial diagnosis impacted patient care most notably in the ER+ setting. The results led to the immediate implementation of direct reflex testing of all newly diagnosed ER+ and HER2-or IHC 2+ cancers by pathology after the initial pilot phase.

3.
Cancer Research ; 82(4 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1779443

ABSTRACT

Background:. Mammographic screening programmes have been shown to reduce breast cancer mortality. However, they detect many small tumours with favourable biological features which may not progress during a woman's lifetime. These are treated with standard surgery and adjuvant therapies, which have associated morbidities. Thus, there is a need to reduce overtreatment of good prognosis tumours found by screening. Minimally invasive treatment approaches have been described but there is no prospective randomised evidence to support their routine use. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Methods:. SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screen-detected good prognosis breast cancers. The main eligibility criteria are age ≥47 years, screen-detected unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in S the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are:1.Non-inferiority comparison of the requirement for a second procedure following excision2.Single arm analysis of local recurrence (LR) at 5 years following VAE. Recruitment of 800 patients over 4 years will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A QuinteT Recruitment Intervention (QRI) is integrated throughout SMALL to optimise recruitment and informed consent. Recruitment challenges are identified by analysing recruiter/patient interviews and audio-recordings of trial discussions, and by review of screening, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Results:. SMALL opened in December 2019, but recruitment halted in 2020 due to suspension of the NHS BSP for 5 months due to COVID-19. As of 1st July 2021, 55 patients had been approached in 10 centres, with 33 patients randomised (randomisation rate 60%). A further 23 centres are in set-up, with 8 suspended due to the pandemic. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on introducing and discussing SMALL, providing balanced information. on treatment options and explaining randomisation). individual recruiter feedback has commenced, with wider feedback planned shortly. Conclusion:. Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes. SMALL is funded by the UK NIHR HTA programme, award 17/42/32.

4.
British Journal of Surgery ; 109(SUPPL 2):ii1-ii2, 2022.
Article in English | EMBASE | ID: covidwho-1778893

ABSTRACT

Introduction: Locally advanced differentiated thyroid cancer (LADTC) management depends on a complex interplay of patient and tumour factors. When primary resection cannot be achieved, neoadjuvant tyrosine kinase inhibitor (TKI) therapy can be considered, but little evidence is available on its success and outcomes. Our aim was to describe a small series of LADTC managed with neoadjuvant TKI therapy. Methods: Suitable patients were prospectively identified in NHS Lothian February 2016 - March 2020. Results: Four patients were eligible for inclusion, 3 females;1 male, aged 39-79 years. All were T4a at presentation;three papillary and one Hurthle cell carcinoma. One had pulmonary metastases. Two refused laryngectomy, one was deemed unresectable with extensive tracheal involvement, and one commenced TKI due to COVID-19 related surgical delay. TKI treatment length varied from 1-18 months. There was a marked reduction in tumour volume and local extent in three cases, such that surgical resection without laryngectomy could be achieved. The fourth patient was intolerant of TKI. All ceased TKIs 2 weeks prior to total thyroidectomy, with neck dissection in three, and tracheal resection and re-anastomosis in two. All then had 3700MBq RAI and all patients are currently alive with 14-58 months follow-up. Two patients have no evidence of residual or recurrent disease. The M1 patient has stable low-volume local and distant disease, and one patient has stable low volume indeterminate pulmonary nodules. Conclusion: Neoadjuvant TKI therapy in LADTC can be effective in reducing primary tumour extent to potentially facilitate limited surgical resection in a highly selected patient group.

5.
British Journal of Surgery ; 109(SUPPL 1):i50, 2022.
Article in English | EMBASE | ID: covidwho-1769177

ABSTRACT

Aim: During the COVID-19 pandemic, the training opportunities were markedly disrupted particularly, the surgical teaching which usually requires face to face teaching to help the acquisition of procedural skills. We implemented a QI project in a district hospital to improve the training opportunities for medical students & foundation doctors. The project was a face-to-face free course for teaching generic procedural and clinical skills in surgery. Method: The course was a mixture of two well-known surgical courses in the UK, Basic Surgical Skills and the CCrISP courses. It included clinical and procedural skills sessions on models which simulated the basic wound closure techniques and types of knots, as well as skin lesion excision training. The course was delivered to medical students, foundation year one & two doctors and core surgical trainees. The improvement achieved by the course was measured by a questionnaire assessing the level of confidence between the candidates before and after each session. The questionnaire's answers were categorised into (not confident, neutral, confident & very confident). The course was delivered on two occasions. Results: The qualitative analysis of the results on two different occasions showed a considerable improvement in the level of confidence between the candidates. They were able to demonstrate engagement throughout the course especially with the procedural skills sessions. Conclusions: Formulating a course at a local hospital level was an efficient alternative for maximising the training opportunities reduced during the pandemic. It was an impressive opportunity for newly graduated doctors and medical students having any surgical placement.

6.
British Journal of Oral and Maxillofacial Surgery ; 60(1):e3, 2022.
Article in English | EMBASE | ID: covidwho-1757162

ABSTRACT

Introduction: Tumour size, depth of invasion, type and extent of nodal metastasis are some of the key prognostic indicators in operable head and neck cancers. Initial Imaging with USS of neck and FNAC or core biopsy has been established to have a high sensitivity and specificity. In addition, CT neck and thorax and MRI scan of the primary tumour are recommended as part of staging scans. Information from this work up guides the MDT and patients towards a tailored management plan. We aimed to compare preoperative imaging work up and TNM staging with post-operative histopathology. Methods: We retrospectively reviewed 48 patients who underwent resection and selective neck dissection from January 2020 to August 2021, assessing their initial work up and its adherence to current guidelines. We also evaluated its correlation to final histopathology. Results: 100% compliance was noted with USS and FNAC, 94% compliance with CT and MRI and 96% had incisional biopsy. USS showed a 80 % specificity and a 55% sensitivity. CT had a specificity of 62.5% and sensitivity of 75%. MRI specificity was 58.8% and sensitivity 73.6%. Conclusions: Our results compare favourably to other published data on imaging correlation to histopathology in head and neck oncology. Time lapse between preoperative work-up and surgical resection during COVID pandemic may have led to advanced disease that is not evident on preoperative staging scans. Newer modalities including real time imaging and in-vivo surgical margin assessment remain to be explored.

7.
Breast ; 56:S87, 2021.
Article in English | EMBASE | ID: covidwho-1735085

ABSTRACT

Goals: There is no doubt, that Severe Acute Respiratory Syndrome Coronavirus-2 and it’s associated disease (COVID19) has been quite challenging not only for all Health Systems worldwide, but also for all medical professionals, particularly those dealing with cancer patients. There has been a rearrangement of healthcare resources, so that the health systems to be able to deal with the high volume of covid19 patients and the required facilities for their treatment. As a result, routine treatment pathways have been modified. Surgical management of breast cancer patients could not be exempted from treatment pathway modification in the covid19 outbreak era. Main goal is to reduce hospital stay and minimizing the risk for complications and consequently hospital visits, facilitating at the same time oncologic efficiency. Aim of this study is apart from comparing breast surgery cases in two consecutive years, to evaluate the efficacy of therapeutic mammoplasty in breast cancer patients in Covid Outbreak era. Methods: We compared all the breast cases done by a Consultant Oncoplastic Breast Surgeon during covid19 outbreak from March until June in 2020 to the cases done during the same period of time in 2019. Parametres like tumor characteristics, hospital stay, complications, oncologic efficacy, and cosmetic outcome were evaluated. Results: Asseen in theTable1, all breast cases duringCovid19outbreak were cancer cases, without any reconstruction or surgery for benign breast diseases. The number of cases in total was slightly smaller during the outbreak, compared to ones in 2019. As anticipated, there was no reconstruction or benign cases surgery during Covid19 in compliance with Association of Breast Surgery recommendations and regional/national guidelines during Covid19 outbreak. In terms of Wide Local Excisions all of our cases underwent therapeutic mammoplasties, mainly with Modified Round Block technique. (Table Presented) Conclusion(s): In view of Covid19 outbreak, surgical approach to breast cancer patients should ensure oncologic efficiency and minimize exposure to hospital environment. As our data demonstrate, therapeutic mammoplasty is a safe and oncologically efficient approach for breast cancer patients, with minimum complication rates and high satisfaction rates in terms of cosmesis. Therefore, even in challenging pandemic times we are, it can be safely performed by trained Oncoplastic Surgeons. Conflict of Interest: No significant relationships.

8.
Breast ; 56:S74, 2021.
Article in English | EMBASE | ID: covidwho-1735080

ABSTRACT

Goals: Wire-guided localisation (WGL) has been the standard technique for pre-operative localisation of non-palpable breast cancer (NPBC) for almost 40 years. However,WGL has several pitfalls including peri-operative scheduling challenges and patient discomfort. Savi Scout localisation (SSL) is a novel FDA-approved potential alternative, that utilises an implantable wireless non-radioactive reflector. A systematic review and meta-analysis was performed to compare the surgical outcomes of SSL versus WGL in NPBC surgery. Methods: Embase, MEDLINE, PubMed and the Cochrane Library (1946 to December 2020)were searched using PRISMA guidelines for studies comparing SSL andWGL in NPBC surgery. Outcome measures including operative duration, positive margins and re-excision were analysed. Results were pooled into meta-analyses using a Mantel- Haenszel Random-Effects model as Odds Ratios for dichotomous data and Mean Difference for continuous data with a 95% Confidence Interval. Results: Four eligible peer-reviewed studies involving 808 patients were identified comparing SSL (n = 462) andWGL (n = 346), including one prospective and three retrospective cohort studies. Therewas no significant difference between SSL and WGL in operative duration (minutes) (95% CI -0.27, -7.89 to 7.34, p = 0.94), positive margins (OR 0.73, 0.36 to 1.45, p = 0.36) and re-excision (OR 0.62, 0.33 to 1.16, p = 0.13). Inclusion of two excluded non-peer-reviewed retrospective cohort studies (additional SSL n = 143,WGL n = 424) altered statistical significance for re-excision in favour of SSL (OR 0.55, 0.36 to 0.83, p = 0.004). Conclusion(s): This study provides evidence that SSL is a safe and effective alternative to conventional WGL for NPBC surgery. SSL has the advantage of uncoupling pre-operative localisation from surgery, reducing scheduling challenges. This is particularly useful in the current COVID-19 climate, with pre-operative elective surgery patient self-isolation requirements. SSL may decrease the need for reexcision however further studies including randomised controlled trials are required to investigate this further. Conflict of Interest: No significant relationships

9.
Breast ; 56:S61-S62, 2021.
Article in English | EMBASE | ID: covidwho-1735078

ABSTRACT

Goals: The COVID-19 pandemic continues to strain healthcare systems globally. The ESMO COVID-19 adapted recommendations1 advocate for the use of pre-operative/neoadjuvant endocrine therapy as a strategy to defer surgery by 6–12 months in clinical stage I-II breast cancers to prioritize resources for patients that require urgent care. Accurate risk assessment is an integral component of this prioritization process. Adjuvant studies such as MINDACT showed that up to 46% of clinically high risk tumors were classified as genomic Low Risk with MammaPrint, and still have excellent outcomes at 8-yrs with endocrine therapy alone, highlighting the potential for overtreatment if using clinical-risk alone. Here, gene expression results with MammaPrint (MP) and BluePrint (BP) were compared between pre-operative core needle biopsy (CNB) and postoperative surgical resection (SR) specimens to evaluate test performance across specimen type. Methods: 10,574 routine diagnostic samples from outside the US submitted to Agendia between Jan 2017 and Oct 2020 were included in this study.MP and BP testingwere processed according to standard FFPE microarray procedures. MP was used to stratify samples into Ultra LowRisk (UL), LowRisk (LR), and High Risk (HR). BPwas used to classify samples into Basal, Luminal or HER2-type. MP Index (MPI) distribution on BP defined Luminal-type tumors were compared between CNB and SR samples. Comparative “logistics metrics” (avg. turnaround time [TAT] and success rate) were also assessed between these specimen types. Results: 10% of samples were CNB and 90% were SR (Table 1). BP Basal, Luminal and HER2-type distributions were 2%, 97%, and 1% respectively for CNB samples and 1%, 98.6%, and 0.4% respectively for SR samples. Within Luminal-type tumors (majority of the samples), the frequency of UL, LR, and HR results were 14%, 61%, and 39% for CNB, and 13%, 58%, and 42% for SR, respectively. Overall, MP Index distributions were similar between samples tested from CNB vs. SR. Average TAT and success rate % between CNB and SR were similar (Table 2).(Table Presented)Definitions: Turnaround Time (TAT) is calculated from the time a specimen is received at the laboratory to the time a result is available. Success % excludes test failures due to insufficient RNA yield % and sub-optimal RNA quality, and evaluates the total number of specimens that have met the pre-requisite 30% minimum invasive tumor requirement that have a valid result. Conclusion(s): The frequency of each MP risk group as well as the distribution pattern of MP Index were essentially identical between CNB and SR samples, indicating comparable performance regardless of specimen type. With timely TAT and no meaningful difference in MPI distribution between CNB and SR specimens, pre-operative use of MP+BP genomic testing on CNB can be incorporated into the preoperative treatment decision making process. Conflict of Interest: Employee of Agendia, equity/stock ownership interest.

10.
Heart Lung and Circulation ; 30:S208, 2021.
Article in English | EMBASE | ID: covidwho-1734421

ABSTRACT

Introduction: A paucity in data exists regarding the expected growth rate of myxomas given the prompt transition to surgical intervention on initial discovery. Most case reports describe an initial normal echocardiogram compared with a subsequent echocardiogram revealing a myxoma at the time of diagnosis [1-3]. Uniquely, our case follows the sequential monitored growth of an atrial myxoma with transoesophageal images over a 19-month period. Case: This case describes a 71-year-old woman with a history of hypertension and hypercholesterolaemia admitted with a provoked deep vein thrombosis. This was complicated by bilateral pulmonary emboli and a presumed paradoxical embolus through a patent foramen ovale (PFO) resulting in a middle cerebral artery stroke. She was thrombolysed, then managed with rivaroxaban. During PFO closure, intraoperative transoesophageal echocardiogram (TOE) revealed a new left-sided atrial mass 1.0cm x 0.6cm in size, resulting in procedure abandonment. Uncertainty around diagnosis in addition to delays related to the COVID-19 pandemic led to serial imaging. The mass was monitored via TOE at 5, 11 and 19 months, revealing an initially stable then unexpected rapid progression to a size of 3.6cm x 2.9cm in the final 8 months. The patient had prompt excision of her myxoma and patch closure of interatrial septum. Discussion: This case exhibits a rare opportunity to appreciate the visual progression of an atrial myxoma and the unpredictable rapid growth over an 8-month period, highlighting the importance of interval monitoring of undifferentiated atrial lesions. [Formula presented]

11.
Journal of Crohn's and Colitis ; 16:i533-i534, 2022.
Article in English | EMBASE | ID: covidwho-1722347

ABSTRACT

Background: Our objective is to evaluate the serologic response to the SARS-CoV-2 vaccine in patients with Inflammatory Bowel Disease (IBD). In addition to that, we want to analyze the influence of immunosuppressive drugs in that response, as well as describe the adverse events in this population. Methods: We included 266 patients in a unicentric prospective study. All patients signed informed consent. A serologic blood test was made days before the first dose and 2-4 weeks after the complete immunization. We used Siemens Atellica Anti-SARS-CoV-2 (N) and Vircell Virclia (S and N) electrochemiluminescence immunoassay to detect antibodies to SARS-CoV-2). If they were discordant, the results were considered as undetermined. The IBD treatment was stable along the study. The statistics analysis of data was done with Stata 16. Results: Basal characteristics are described in table 1. The patients were on treatment with: 15 (5.66%) had no treatment, 47 (17.7%) had mesalamine, 4 (1.51%) had corticosteroids, 41 (15.47%) had immunomodulator, 113 (42.64%) had biologic and 45 (16.98%) had combo. Amongst the biologic drugs: Infliximab 51 (32,3%), Adalimumab 50 (31,6%), Vedolizumab 19 (12,03%) y Ustekinumab 31 (19,6%). The vaccines were messenger RNA BNT162b2 (Pfizer-BioNTech) in 154 12 months are presented as a real world evidence (RWE) comparison of UST vs anti-TNF. Methods: After exclusion of other biologics than UST and anti-TNF and missing outcomes, the final sample consisted of 607 CD-patients. Clinical remission (HBI ≤ 4) was the predefined endpoint at month 12. Patients were analyzed on a modified intent-to-treat basis (mITT;switchers considered as outcome failure). To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results: 343 UST (naïve: 35) and 264 anti-TNF (naïve: 175) (ADA 61%, IFX 39%) CD-patients were included. PS removed systematic differences between both groups (mean of both groups: 15% perianal disease, 36% surgical resection, 41% EIM). Overall, the number of switches was lower in the UST group than in the anti- TNF group (Tab. 1). However, the number of switches within 12 months was significantly lower in the UST group only when compared to the IFX group (16.3% vs 27.2%;p=0.045) (Fig. 1). Clinical remission rates at 1 year (Tab. 2) were not statistically different for the overall UST vs. anti-TNF groups (65.8% vs 60.0%). Remission rates were similar for UST vs ADA, while these were significantly higher for UST vs. IFX (61.6% vs 41.8%;p=0.009). Looking at clinical remission in the week 16 responder group (Tab. 3), a statistically significantly higher remission rate was found in the overall group for UST (77.6%) vs anti-TNF (65.4%) (p=0.041), which was mainly driven by the higher UST remission rate in biologic-naïve CD patients (p=0.026). Conclusion: This 1-year maintenance phase RWE-comparison with UST vs anti-TNF showed remarkably high clinical remission rates in both groups. Also due to a more frequent switching within the IFX group, the clinical remission rate at 1 year was significantly higher with UST than with IFX and higher with UST vs anti-TNF in the biologic-naïve groups. These results support together with the known favorable safety profile consideration of UST as a first-line targeted therapy for CD.

12.
European Journal of Surgical Oncology ; 48(2):e85, 2022.
Article in English | EMBASE | ID: covidwho-1719674

ABSTRACT

Background: The Covid Pandemic has influenced how cancer surgeries are performed and their pre-operative management to allow appropriate social distancing and self-isolation prior to Surgery. With the requirement of wire localisation of non-palpable breast cancers/ lesions on the day of surgery and non-availability of mammogram and ultrasound machine in an isolated zone, we embarked on localisation of non-palpable breast lesions using MagseedR markers and SentimagR localisation system. We describe our initial experience in the management of these cancers and diagnostic excision biopsies using Magseed. Materials and Methods: Forty consecutive female patients, median age 61 (range 36-84) years underwent Magseed insertion for diagnostic excision biopsy (n=4) and breast conservation surgery (WLE;n= 36). Check mammograms were performed following Magseed insertion to confirm appropriate localisation. During the initial audit of 16 patients, one Magseed guided WLE and sentinel node biopsy was abandoned due to erratic signal strength on the day of surgery and underwent surgery with wire localisation on a later date. Subsequently all cases had Magseed signals confirmed following insertion in the radiology department along with check mammograms. Results: Thirty-nine patients underwent successful breast surgery (Magseed in intra-operative specimen X-ray) with standard axillary procedures (29 sentinel node biopsy, 2 axillary node clearance). The median time from magseed insertion to surgery was 13 (range 3-38) days. The lesions were invasive neoplasm +/- insitu (DCIS) disease (n= 32), DCIS (n=5), and papilloma (n=3). The median overall tumour size was 20 (range 3-38) mm and on postop histology was 17 (2-50) mm. Six patients required further re-excision for margin positivity with DCIS;margins were clear after single cavity shave(n=4) and two patients underwent mastectomy subsequently. Conclusions: Magseed localisation have given us significant flexibility in the management of non-palpable breast cancer and indeterminate lesions requiring diagnostic biopsy during the Covid pandemic. Initial audit suggests usefulness of confirming adequate Magseed signal in the radiology department along with check mammogram during the early learning curve.

13.
JACC: CardioOncology ; 4(1):S5, 2022.
Article in English | EMBASE | ID: covidwho-1676781

ABSTRACT

Background: In 2017 a middle-aged woman with a hypercoagulable state on warfarin was found to have pulmonary emboli and a left upper lung mass on computed tomography (CT). A mass on the pulmonic valve was also identified on echocardiography. Patient History: Thorascopic biopsy of lung mass confirmed spindle cell carcinoma with sarcomatoid features. No metastatic disease was suggested by Positron emission tomography (PET) imaging showing no avidity. Left pneumonectomy was planned. Nuclear stress testing was low risk. Cardiac magnetic resonance (CMR), transthoracic echo (TTE) and transesophageal echo identified a 11 x 6 mm mobile mass on the right pulmonic valve cusp, with mild tricuspid regurgitation (TR) and moderate pulmonic insufficiency (PI). The mass characteristics by CMR suggested a fibroelastoma and not metastasis, thrombus or vegetation. The working diagnosis was a fibroelastoma requiring observation and medical therapy for PI/TR. At pneumonectomy, 3 of 19 N1 nodes were involved and all N2 nodes were clear. She received 4 cycles of adjuvant cispaltin and docetaxel for T2N1M0/stage II spindle cell carcinoma, followed by surveillance. Exams and Imaging: In 2019, she complained of new dyspnea;a CMR was recommended. Chest CT was negative for recurrence. The patient deferred follow up during COVID-19 pandemic until April 2021, when CMR revealed known pulmonary mass was now enlarging, 19 x 14 mm, extending into the outflow tract, with moderate PI and severe TR. The pulmonary artery and right ventricle were dilated. By TTE, pulmonary systolic pressure was estimated at 71 mmHg. The LVEF was preserved. Treatment Plan: After a multidisciplinary discussion, cardiac surgery was recommended. Due to mediastinal shift post lung resection, anterolateral clamshell approach was utilized for enbloc resection with placement of Cryolife 29 mm pulmonary homograft and 31 mm Mosaic porcine tricuspid valve. The pulmonic mass pathology revealed intimal pleomorphic sarcomatoid neoplasm, clonally related but molecularly distinct from her prior tumor. Patient Outcomes: The patient recovered well and dyspnea resolved;the current treatment strategy is surveillance without chemotherapy or radiation. Clinical Implications: This case illustrates that sarcomatoid masses frequently lack PET avidity and lack suspicious features by CMR. A high index of suspicion must be considered even in the setting of benign appearing images.

14.
Cogent Medicine ; 8, 2021.
Article in English | EMBASE | ID: covidwho-1617059

ABSTRACT

Background: Coronavirus disease 19 (COVID-19) tends to be milder in children, but severe cases have been reported. We described a case report of a toddler admitted to our department with additional findings, highlighting the importance of assessing the patient as a whole. Case Presentation: A previously healthy, 15-month-year-old girl presented with fever and dry cough for 10 days, respiratory distress and PCR SARS-CoV-2 was positive. At admission, she presented with hypoxemia (SpO2 89-90% in room air), global retraction and bilateral bronchospasm. She was treated with bronchodilators, methylprednisolone, remdesivir and also amoxicillin/clavulanic acid. Her complete blood count revealed leucocytosis 16,160x109/L, 41% lymphocytes, C-reactive protein 57,9 mg/L, procalcitonin 0,13 ng/mL, sedimentation rate 44 mm/h, ferritin 218,4 ng/mL. Chest computed tomography (CT) scan revealed bilateral peripheral areas of ground glass, coexisting consolidation areas at inferior lobes but also revealed a 6 cm supra-renal mass. Abdominal ultrasound and CT confirmed an heterogeneous right supra-renal gland mass of 5,5cm along the greatest diameter with diffuse calcifications, evolving the inferior vena cava and the renal vascular pedicle, no signs of liver, bone, cutaneous or ganglionic metastization. These features were suggestive of neuroblastoma in stage L2. Vanillylmandelic acid, normetanephrine/creatinine ratio and metanephrine/creatinine ratio were elevated. The metaiodobenzylguanidine (Mibg) scan showed a localized disease. The total excision of the tumour mass was performed, and the histology confirmed neuroblastoma with no N-myc oncogene amplification, nor other bad prognosis chromosomal abnormalities. She is currently under oncological surveillance, with no signs of recurrence. Learning Points Discussion: Neuroblastoma is the most common extracranial solid tumour of childhood. It is known for its broad spectrum of clinical behaviour and outcome. In this case, although this toddler was admitted due to COVID-19 pneumonia, it allowed to identify a localized tumour, perform excision and due to the favourable biology tumour, she has a very good chances of being cured and free of disease.

15.
Blood ; 138:4555, 2021.
Article in English | EMBASE | ID: covidwho-1582176

ABSTRACT

Introduction: Patients (pts) with primary refractory or relapsed high-grade lymphoma (HGL) including Burkitt lymphoma (BL) and high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 (double-hit lymphoma, DHL) have a dismal prognosis with patients almost never achieving a meaningful remission to second line therapy. No standard second line therapeutic approach exists, particularly for BL. The characteristic hallmark of these diseases is a dysregulated MYC oncogene with both downstream effects on proliferation and a high metabolic fluxes which use tricarboxylic acid (TCA) cycle intermediates as biosynthetic precursors. CPI-613 (devimistat) is a non-redox active analogue of lipoic acid, a required cofactor for two key mitochondrial enzymes of the TCA cycle, pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase. Disruption of mitochondrial function by CPI-613 results in a shutdown of ATP and biosynthetic-intermediate production, leading to cancer cell death by apoptosis or necrosis. In the initial phase I trial (n=26) one patient with multiply refractory BL had a partial remission sustained for over one year and then consolidated by surgical resection. She remains alive 7 years later. As of July 2021, 20 clinical studies for various cancers have been conducted (ongoing/completed) with devimistat with over 700 patients having received study drug. We initiated a phase II trial to further explore efficacy in HGL. Devimistat has FDA orphan status for BL and 4 other cancers. Methods: NCT03793140 is a multicenter study aiming to enroll 17 patients on each of two cohorts, BL and DHL, with a Simon's 2-stage design for each cohort, requiring one response among the first 9 treated patients to expand to 17. Patients must have had at least one prior line of therapy or are refusing standard of care and must be more than 3 months after a prior stem cell transplant. Active central nervous system (CNS) parenchymal disease is excluded, but prior leptomeningeal disease is allowed if the CSF is negative for more than 4 weeks at enrollment and maintenance intrathecal therapy is ongoing. Devimistat is given by central line over 2 hours daily x 5 days for two 14-day cycles and then as maintenance x5 days every 21 days. Pts were evaluable for response if they received at least 4 infusions over 5 days of the first cycle. Results: 9 pts were enrolled in the DHL/THL arm. Mediannumber of prior therapies were 3 (range, 1-6). No responses were seen, with only 1 patient achieving stable disease as best response, resulting in cohort closure. Thus far, 8 BL pts were enrolled. Median number of prior therapies was 3 (range, 2-4). Two patients were inevaluable for response. 1/6 patients had stable disease through cycle 7 and one had a complete response (CR). This CR patient (HIV+) with 4 prior therapies entered the study with only a biopsy proven thigh mass. He was not a transplant candidate for social reasons. He had a near complete metabolic remission after 4 cycles of devimistat and a CR after cycle 7. (Table and Figure) As of July 2021, he is in cycle 11, having had a 4-week treatment delay of cycle 5 due to CoVID 19 infection. ECOG improved from 3 to 0. Adverse events (AE): As of July30, 2021, no patient experienced a serious adverse event related to study drug. Four patients had grade 3 events at least possibly related: 2 neutropenia, 1 thrombocytopenia and 1 elevated bilirubin. 1 patient had a dose reduction for grade 2 alanine aminotransferase increase. Conclusions: Although our results are preliminary, the complete remission in this patient is promising in a disease where no viable treatment options exist in the relapsed, refractory BL. Enrollment to the BL cohort is ongoing. [Formula presented] Disclosures: Nikolaenko: Pfizer: Research Funding;Rafael Pharmaceuticals: Research Funding. Pardee: Celgene/BMS: Consultancy, Speakers Bureau;Amgen: Consultancy, Speakers Bureau;Pharmacyclics: Consultancy, Speakers Bureau;Janssen: Consultancy, Speakers Bureau;AbbVie: Membership on an entity's Board of Directors or advisor committees;CBM Biopharma: Membership on an entity's Board of Directors or advisory committees;Karyopharm: Research Funding;Rafael Pharmaceuticals: Research Funding. Abramson: Genentech: Consultancy;Kymera: Consultancy;Karyopharm: Consultancy;AbbVie: Consultancy;Seagen Inc.: Research Funding;Allogene Therapeutics: Consultancy;Astra-Zeneca: Consultancy;Incyte Corporation: Consultancy;BeiGene: Consultancy;Bluebird Bio: Consultancy;Genmab: Consultancy;EMD Serono: Consultancy;Bristol-Myers Squibb Company: Consultancy, Research Funding;C4 Therapeutics: Consultancy;Morphosys: Consultancy;Kite Pharma: Consultancy;Novartis: Consultancy. Horwitz: Vividion Therapeutics: Consultancy;Shoreline Biosciences, Inc.: Consultancy;Tubulis: Consultancy;Verastem: Research Funding;ONO Pharmaceuticals: Consultancy;Myeloid Therapeutics: Consultancy;SecuraBio: Consultancy, Research Funding;Trillium Therapeutics: Consultancy, Research Funding;Seattle Genetics: Consultancy, Research Funding;Millennium /Takeda: Consultancy, Research Funding;Kura Oncology: Consultancy;Janssen: Consultancy;Kyowa Hakko Kirin: Consultancy, Research Funding;Forty Seven, Inc.: Research Funding;Daiichi Sankyo: Research Funding;C4 Therapeutics: Consultancy;Celgene: Research Funding;Aileron: Research Funding;Affimed: Research Funding;Acrotech Biopharma: Consultancy;ADC Therapeutics: Consultancy, Research Funding. Matasar: GlaxoSmithKline: Honoraria, Research Funding;Teva: Consultancy;Janssen: Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;IGM Biosciences: Research Funding;Merck: Consultancy;Juno Therapeutics: Consultancy;TG Therapeutics: Consultancy, Honoraria;Seattle Genetics: Consultancy, Honoraria, Research Funding;Memorial Sloan Kettering Cancer Center: Current Employment;Pharmacyclics: Honoraria, Research Funding;Daiichi Sankyo: Consultancy;ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria;Rocket Medical: Consultancy, Research Funding. Noy: Rafael Parhma: Research Funding;Morphosys: Consultancy;Targeted Oncology: Consultancy;Medscape: Consultancy;Pharmacyclics: Consultancy, Research Funding;Janssen: Consultancy, Honoraria;Epizyme: Consultancy. OffLabel Disclosure: CPI-613 (devimistat) is a non-redox active analogue of lipoic acid, a required cofactor for two key mitochondrial enzymes of the TCA cycle, pyruvate dehydrogenase and alpha ketoglutarate dehydrogenase. Disruption of mitochondrial function by CPI-613 results in a shutdown of ATP and biosynthetic-intermediate production, leading to cancer cell death by apoptosis or necrosis

16.
Arquivos Brasileiros De Cardiologia ; 117(6):1217-1218, 2021.
Article in English | Web of Science | ID: covidwho-1579172
17.
British Journal of Surgery ; 108(SUPPL 6):vi83, 2021.
Article in English | EMBASE | ID: covidwho-1569598

ABSTRACT

Leukocytoclastic vasculitis (LV) is an inflammation of the small vessels in the dermis characterised by the deposition of immunocomplexes in the involved vessel walls. It commonly manifests as palpable purpura, limited to the skin and predominantly of the lower limb. We report a rare case of necrotising LV (NLV) affecting bilateral breast, manifesting clinical features of necrotising fasciitis (NF), and emphasizes the potential diagnostic challenges that markedly influence the treatment and survival of patients. A 48-year-old female presented with an acute onset left breast skin necrosis and discolouration that rapidly progressed to the contralateral breast with surrounding erythema and oedema of the chest wall yet spared the intermammary cleft. Some non-blanching purpuric rash were also noted on upper abdomen and left lower limb. COVID-19 test was negative. CT scan showed extensive bilateral breast fat stranding and oedema. Patient became clinically septic with a moderately raised CRP and mild acute kidney injury. Radical mastectomies and chest wall excision were performed with intra-operative findings of cloudy fluid and easily peeled away subcutaneous tissue from fascia. Urgent gram stain and culture showed no organisms. Tissue biopsies subsequently showed the diagnosis of NLV. Chest wall defect was then reconstructed with split skin grafts, NLV treated with corticosteroids and patient made an uneventful recovery. This case highlights the incidence of a rare and aggressive manifestation of NLV on the breast that mimics NF, emphasizing the clinical differentiation that may lead to catastrophic results and significant cosmetic defect, if a differential diagnosis cannot be determined at the time.

18.
British Journal of Surgery ; 108(SUPPL 6):vi71-vi72, 2021.
Article in English | EMBASE | ID: covidwho-1569597

ABSTRACT

Aim: Wire guided localisation(WGL) to localise non-palpable breast tumours has been the standard for years. WGL has limitations;patient discomfort, fixed scheduling to facilitate insertion on the day of surgery and wire migration. A 2015 audit in our department found that 51% of patients undergoing wide local excision (WLE) used preoperative localisation techniques;of which 84% was WGL. The overall re-excision rate for WLE was 27%. We altered our practice to Magseed localisation from July 2019 to improve patient experience, and surgical efficiency, as there are similar outcomes between WGL and Magseed in the literature. This audit aims to examine if there are improvements in our re-excision rate. We aim to evaluate which is the best method for localisation in our department. Method: A retrospective audit was conducted following registration with the local audit office. Patients who underwent breast conserving surgery between September 2019 and September 2020 were identified. The surgical approach, re-excision and complications were recorded and compared to the 2015 results. Results: 100 patients underwent WLE in the study period. The percentage of patients undergoing therapeutic mammaplasty was 26% (14% in 2015). 63% underwent preoperative localisation;of which 71% used Magseed and 5% used wire. The overall re-excision rate was 20%. Conclusions: Our re-audit has demonstrated an increase in patients requiring pre-operative localisation, probably due to the use of primary endocrine treatment during COVID-19. We gladly observed 26% improvement in re-excision rates suggesting success with Magseed.

19.
Molecules ; 26(22)2021 Nov 22.
Article in English | MEDLINE | ID: covidwho-1534202

ABSTRACT

The 5',8-cyclo-2'-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered-the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5'-end side of cdPu than on its 3'-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded.


Subject(s)
DNA Damage , DNA Repair , DNA, Mitochondrial/metabolism , Oligonucleotides , Purine Nucleosides , Animals , CHO Cells , Cricetulus , Oligonucleotides/chemistry , Oligonucleotides/pharmacology , Purine Nucleosides/chemistry , Purine Nucleosides/pharmacology
20.
J Plast Reconstr Aesthet Surg ; 75(2): 722-729, 2022 02.
Article in English | MEDLINE | ID: covidwho-1458808

ABSTRACT

BACKGROUND: A cohort study of patients, who underwent cutaneous squamous cell carcinoma (SCC) excision, was undertaken to evaluate the effects of the COVID-19 pandemic on treatment times and histopathological features. METHODS: We identified all patients who had SCCs excised in October 2020 (pandemic group); the control group included all patients who underwent excision of SCCs during October 2019 (pre-pandemic group). Collected data included SCC subtype, thickness, size, clearance margins, referral details, patient comorbidities and operative data. RESULTS: There were 140 patients (174 SCCs; pre-pandemic group=74; pandemic group=100) identified for study inclusion. Both groups were well matched for age, sex, previous history of cancer, cutaneous SCC and histological subtype. There was a delay in median patient presentation time to the GP in the pandemic versus pre-pandemic group (106 days vs. 56 days, p <0.001); this led to a longer overall time to surgery (167 days vs. 110.5 days, p < 0.001). Pandemic group SCCs had larger median Breslow depths (4 mm vs. 3 mm, p = 0.01), a greater proportion of Clark's level 4 and 5 lesions (76.9% vs. 61.1%, p = 0.03), and a higher rate of high (20-40 mm) and very high (>40 mm) risk SCCs as defined by British Association of Dermatology diameter criteria (56.1% vs. 39.2%, p = 0.03), versus the pre-pandemic group. CONCLUSIONS: There was a 57-day median SCC treatment delay, and an associated development of higher risk SCCs by the time of surgery. Despite the challenges of a pandemic, patients should seek early consultation for suspicious skin changes, and healthcare systems should maintain skin cancer treatment pathways.


Subject(s)
COVID-19 , Carcinoma, Squamous Cell/surgery , Skin Neoplasms/surgery , Time-to-Treatment , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male
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