Triple Negative Male Breast Cancer (2021)

Type of publication:
Conference abstract

Author(s):
Qavi Q.; Alkistawi F.; Lesi O.; Asaad A.; Abdalla Al-Zawi A.S.; Abraham B.; Kumar S.; Ahmed R.; Barron M.; Arooj *Khan K.; Syed A.; Deniz E.; Abduljawad N.H.; Idaewor P.; Aladili Z.; Rasheed N.; Eldruki S.; Uddin A.

Citation:
European Journal of Surgical Oncology; Feb 2021; vol. 47 (no. 2)

Abstract:
Background: Male breast cancer (MBC) is a rare malignancy, may present at advanced disease stage. Triple negative breast cancer (TNBC) known to have the poorest prognosis of all other histological types of breast cancer. This paper presents a case of 71 years old gentleman diagnosed with TNBC. Material(s) and Method(s): A 71 years old male patient, presented with a right breast lump of a recent history also has chronic kidney disease, gastroesophageal reflux,, and excision of basal cell carcinoma of abdominal wall. Clinically he had a skin dent and apalpable 3cm lump underneath in the right breast axillary tail. Mammogramand breast US showed suspicious lesion in right breast axillary tail in additionto a suspicious lymph node in right axilla. Imaging guided core biopsies weretaken from the breast and axillary abnormalities. The histology revealed grade1 invasive ductal carcinoma NST, ER 0 and PR 0 and HER 2 negative. The Breast Multidisciplinary Team meeting advised for mastectomy and axillary clearance, this has been performed. The postoperative Pathomorphology report revealed 23 mm triple negative invasive ductal carcinoma NST, grade 1with Ki67 10%, T2N1M0. The postoperative MDT recommended annual surveillance with mammogram for 5 years. Result(s): MBC is very rare, it is the cause of 1% of all malignant diseases in men, andcauses < 1% of all breast cancers in both males and females.MBC is diagnosed at an average of 10 years later than the age at which breast cancer is diagnosed in females at 65 years of age.There are some reported risk factors associated with MBC as, cryptorchidism, family history, Klinefelter's syndrome, infertility and smoking. Also it has been reported that Only 1/3 of male patients who have BRCA1/2 mutation maydevelop malignancy of breast, pancreas and prostate. Similar to female breast cancer, the most histological type of male breast cancer is invasive ductalcarcinoma NST, and the oestrogen hormone receptors expression is greaterthan in females (up to 95%).Male triple negative breast cancer (MTNBC) is associated with aggressivedisease course, late stage of diagnosis, large size of the tumour size, hightumor histological grade, and high rate nodal disease, also is reported more in a younger patients.Mastectomy is the mainstay of surgical treatment and the triple-negative breast cancer generally has a better to chemotherapy than tumours with oestrogen hormone-receptor positive expression. Adjuvant radiotherapy is recommended, however it doesn't effect the cause-specific survival rate. Conclusion(s): MBC is uncommon entity, accounting for < 1% of all breast cancer diagnosed in both genders and the MTNBC still is rarer, and mastectomy is the mainstay of surgical treatment. in addition to chemotherapy and radiotherapy, however the later doesn't effect the cause-specific survival rate.

Epidemiology, Incidence and Outcomes from Male breast cancer in Mid and South Essex (2021)

Type of publication:
Conference abstract

Author(s):
Alkistawi F.E.; Qavi Q.; Omotara L.; Asaad A.; Salih A.; Chicken W.; Elamass M.; Cathcart P.; Venkat S.E.; Syed A.; Barron M.; *Khan K.; Deniz E.; Abduljawad N.; Aladili Z.; Ozua P.; Idaewor P.; Uddin A.; Rasheed N.; Abdalla Al-Zawi A.S.

Citation:
European Journal of Surgical Oncology; Feb 2021; vol. 47 (no. 2)

Abstract:
Background: Breast Cancer is the most common cancer in the United Kingdom and the second most common cancer in the world. Male breast cancer (MBC) is rare, but reported to account for <1 % of all breast cancer cases and 1% of all male malignancies. The management protocols for male breast cancer are largely derived from the evidence in female breast cancer management.In this study we analysed all MBC within our region presenting over a 6 year period. We are reporting the incidence, clinico-pathological features, management and outcomes of MBC patient treated in 3 breast centres serving the Mid and South Essex region of England. Material(s) and Method(s): Retrospective multicentre review of all the male breast cancer patients presented between 2014 and 2019, in Basildon Hospital, Broomfield Hospital & Southend Hospital. We identified 44 patients and collected data from their clinical records. Data related to patients' age, risk factors, histopathology,surgical treatment, adjuvant treatment and survival were analysed. Result(s): Out of 6952 cases of breast cancer diagnosed between 2014 and 2019, 44 cases of male breast cancer were identified which represents 0.63% of all cases. This lies within the international figures of incidence of male breast cancer. The age group ranged between 43 &96 years with higher incidence on the 9th decade of life. Family history was significantly linked to MBC,in our study and it was observed in 31% of cases.Smoking association with male breast cancer needs to be further assessed in a larger study as in our study group only 3 patients were actively smoking, though another 9 were ex-smokers, this gives a total of 25% of cases associated with smoking history.As for female breast cancer, Invasive ductal carcinoma (IDC) is the most common encountered histological subtype (77%), though other histopathologic subtypes were recorded including invasive lobular carcinoma (4.5%), tubular (4.5%), papillary carcinoma (4.5%) Combined IDC & ILC (2.5%) and DCIS (7%).The receptor status is comparable to the reported figures except for the triple negative cancers which showed a higher rate 6.5% compared to less than 1% rate in documented literature. Mastectomy and sentinel node biopsy remains the main line of treatment, though management with hormonal manipulation only was undertaken in 20% of patients due to frailty or metastatic disease. At a median follow-up of 3 years, 11 patients had died, but only 3 deaths were caused by breast cancer, the mortality rate in our cohort was 25%; however the MBC specific mortality in the cohort was only 6.8%. Conclusion(s): Male breast cancer is rare. It maybe associated with late presentation and less favorable outcomes. Public and health professional education is recommended to enable early disease detection. Multi-centre collaboration is suggested to allow access to a larger database for research to determine the risk factors, optimum treatment and outcomes.

Supratentorial vs infratentorial posterior calvarial distraction osteogenesis for the increase of ICV in children with syndromic or multi-suture craniosynostosis: a retrospective cohort study (2021)

Type of publication:
Journal article

Author(s):
Sharman J.; Rodrigues D.; McGuirk S.; *Panikkar M.; Nishikawa H.; Dover S.; Evans M.; White N.

Citation:
Child's Nervous System; 2021 [epub ahead of print]

Abstract:
Purpose: Craniosynostosis is the premature and pathological fusion of calvarial sutures. One modality of surgical treatment of syndromic craniosynostosis is posterior calvarial distraction (PCD). This can be either supratentorial or infratentorial. Currently, supratentorial PCD may be regarded as safer but produces a smaller increase in calvarial volume compared to infratentorial PCD. This study quantifies and compares the effectiveness of supratentorial and infratentorial PCD to help guide surgical decision-making. Method(s): The CT and/or MRI scans of 47 cases of craniosynostosis who underwent PCD from the Birmingham Children's Hospital (BCH) were converted to sagittal series multi-planar reformatted (MPR) scans for the manual calculation of ICV. The 47 cases were classified as having undergone either supratentorial or infratentorial PCD using lateral plain film radiographs, with 28 and 32 pairs of pre- and post-operative CT/MRI scans reviewed respectively. Result(s): A statistically significant difference between supratentorial and infratentorial PCD was observed for the increase in supratentorial volume (STV) (P = 0.0458) and total intracranial volume (TICV) (P = 0.0437), but not for the increase in infratentorial volume (ITV) (P = 0.0697). The relationship for each volume trended towards convergence but was not achieved before the physical limit of 30 mm distraction had been reached. Intraclass correlation coefficient values for agreement of MRI and CT scans for STV, ITV and total ICV were 0.852, 0.864 and 0.854 respectively. Conclusion(s): Our evidence suggests that supratentorial PCD is more effective for increasing ICV in a clinical setting. CT and MRI imaging modalities are acceptably clinically interchangeable for calculating ICV in craniosynostosis.

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Development and internal validation of clinical prediction models for outcomes of complicated intra-abdominal infection (2021)

Type of publication:
Journal article

Author(s):
Ahmed, S; Bonnett, L; Melhuish, A; Adil, M T; Aggarwal, I; Ali, W; Bennett, J; Boldock, E; Burns, F A; Czarniak, E; Dennis, R; Flower, B; Fok, R; Goodman, A; Halai, S; Hanna, T; Hashem, M; Hodgson, S H; Hughes, G; Hurndalm, K-H; Hyland, R; Iqbal, M R; Jarchow-MacDonald, A; Kailavasan, M; Klimovskij, M; Laliotis, A; Lambourne, J; Lawday, S; Lee, F; Lindsey, B; Lund, J N; Mabayoje, D A; Malik, K I; Muir, A; Narula, H S; Ofor, U; Parsons, H; *Pavelle, T; Prescott, K; Rajgopal, A; Roy, I; Sagar, J; Scarborough, C; Shaikh, S; Smart, C J; Snape, S; Tabaqchali, M; Tennakoon, A; Tilley, R; Vink, E; White, L; Burke, D; Kirby, A

Citation:
The British Journal of Surgery; Apr 30;108(4):441-447

Abstract:
BACKGROUND Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse.METHODS A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further.RESULTS Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was -0.19 (95 per cent c.i. -0.39 to -0.12) and – 0.01 (- 0.17 to -0.03) respectively.CONCLUSION Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, although these require external validation.

The FAST-M complex intervention for the detection and management of maternal sepsis in low-resource settings: a multi-site evaluation (2021)

Type of publication:
Journal article

Author(s):
Cheshire, James; Jones, Laura; Munthali, Laura; Kamphinga, Christopher; Liyaya, Harry; Phiri, Tarcizius; *Parry-Smith, William; Dunlop, Catherine; Makwenda, Charles; Devall, Adam James; Tobias, Aurelio; Nambiar, Bejoy; Merriel, Abi; Williams, Helen Marie; Gallos, Ioannis; Wilson, Amie; Coomarasamy, Arri; Lissauer, David

Citation:
BJOG : an international journal of obstetrics and gynaecology; Jul;128(8):1324-1333

Abstract:
OBJECTIVE To evaluate whether the implementation of the FAST-M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low-resource setting.DESIGNA before and after design.SETTINGFifteen government healthcare facilities in Malawi.POPULATION Women suspected of having maternal sepsis.METHODS The FAST-M complex intervention consisted of the following components: i) the FAST-M maternal sepsis treatment bundle and ii) the FAST-M implementation programme. Performance of selected process outcomes were compared between a two month baseline phase and six month intervention phase with compliance used as a proxy measure of feasibility.MAIN OUTCOME RESULT Compliance with vital sign recording and use of the FAST-M maternal sepsis bundle.RESULTS Following implementation of the FAST-M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 (0%) vs. 169/252 (67.1%), p<0.001). Recognition of suspected maternal sepsis improved with more cases identified following the intervention (12/106 (11.3%) vs. 107/166 (64.5%), p<0.001). Sepsis management improved, with women more likely to receive all components of the FAST-M treatment bundle within one hour of recognition (0/12 (0%) vs. 21/107 (19.6%), p=0.091). In particular women were more likely to receive antibiotics (3/12 (25.0%) vs. 72/107 (67.3%), p=0.004) within one hour of recognition of suspected sepsis.CONCLUSION Implementation of the FAST-M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low-resource setting such as Malawi.

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Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study (2021)

Type of publication:
Randomised controlled trial

Author(s):
Jason Yap, Daniel Slade, Harriet Goddard, Christopher Dawson, Raji Ganesan, Shireen Velangi, *Banchhita Sahu, Baljit Kaur, Ana Hughes, David Luesley

Citation:
BJOG 2021 May;128(6):1047-1055

Abstract:
Objective To compare the safety and efficacy of Veregen® ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). Design A Phase II randomised control trial. Setting A tertiary gynaecological oncology referral center. Population All women diagnosed with primary and recurrence uVIN. Methods Eligible patients were randomised to receive either Veregen® or placebo ointment (applied 3 times daily for 16 weeks), and were followed up at 2, 4, 8, 16, 32 and 52 weeks. Main outcome measures Outcome measures, recorded at 16 and 32 weeks, were histological (HR) and clinical (CR) response (as measured by ≥30% reduction in the sum of the longest diameter of all lesions when compared to baseline), toxicity and changes in quality of life and pain scores. Results 26 patients were randomised and all 13 patients who received Veregen® showed either complete (n=5) or partial (n=8) CR with a trend towards an improvement in baseline symptoms. In placebo group, 3 patients had complete CR, 2 had partial CR and 6 had stable disease. Patients in the Veregen® group showed a significant improvement in CR as compared to the placebo group (P=0.0026). There was no evidence of difference in HR and toxicity reported in both groups. Conclusion Our study indicates that Veregen application is safe and leads to at least a partial clinical resolution of uVIN lesions and symptoms improvement, thus warranting a phase III multi-centre RCT.

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Folic Acid Supplementation in Postmenopausal Women with Hot Flushes: Phase III Randomised Double-Blind Placebo-Controlled Trial (2021)

Type of publication:
Randomised controlled trial

Author(s):
Ayman Ewies, Ikhlaq Ahmed, Farook Alazzawi, Joan Pitkin, Pratima Gupta, Mojca Persic, *Banchhita Sahu, Alaa El-Ghobashy, Lisa Barraclough, Jacqueline Woodman, Jaspreet Babrah, Sarah Bowdem, Deborah Stocken, Lucinda Billingham, Sudha Sundar, Daniel Rea

Citation:
BJOG; November 2021; Volume128, Issue12, Pages 2024-2033

Abstract:
Objective: To assess whether folic acid supplementation ameliorates hot flushes. Design: Double-blind, placebo-controlled randomised trial. Setting: Nine hospitals in England. Population: Postmenopausal women experiencing ≥50 hot flushes weekly. Methods: Women (n=164) were randomly assigned in a 1:1 ratio to receive folic acid 5mg tablet or placebo daily for 12 weeks. Participants recorded frequency and severity of hot flushes in Sloan Diary daily and completed Greene Climacteric and Utian Quality of Life (UQoL) Scales at 4-weekly intervals. Main Outcome Measures: The change in daily Hot Flush Score at week-12 from randomisation based on Sloan Diary Composite Score B calculation. Results: Data of 143 (87%) women was available for the primary outcome. The mean change (SD) in Hot Flush Score at week-12 was -6.98 (10.30) and -4.57 (9.46) for folic acid and placebo group, respectively. The difference between groups in the mean change was -2.41 (95% CI: -5.68, 0.87), p=0.149 and in the adjusted mean change was -2.61 (95% CI: -5.72, 0.49) with p=0.098. There was an increased benefit in the folic acid group regarding changes in total and emotional UQoL scores at week-8 when compared with placebo. The difference in the mean change from baseline was 5.22 (95% CI: 1.16, 9.28) and 1.88 (95% CI: 0.23, 3.52) for total and emotional score, respectively. Conclusions: Folic acid had a greater benefit in reducing Hot Flush Score over 12 weeks in postmenopausal women when compared with placebo; however, the difference did not reach statistical significance. Definitive evidence of benefit requires a larger study.

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Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs (2021)

Type of publication:
Journal article

Author(s):
Joharatnam-Hogan N, Alexandre L, Yarmolinsky J, *Lake B, *Capps N, Martin RM, Ring A, Cafferty F, Langley RE

Citation:
Current Oncology Reports, 13 Feb 2021, 23(3):29

Abstract:
Purpose of review: Repurposing established medicines for a new therapeutic indication potentially has important global and societal impact. The high costs and slow pace of new drug development have increased interest in more cost-effective repurposed drugs, particularly in the cancer arena. The conventional drug development pathway and evidence framework are not designed for drug repurposing and there is currently no consensus on establishing the evidence base before embarking on a large, resource intensive, potential practice changing phase III randomised controlled trial (RCT). Numerous observational studies have suggested a potential role for statins as a repurposed drug for cancer chemoprevention and therapy, and we review the strength of the cumulative evidence here.
Recent findings: In the setting of cancer, a potential repurposed drug, like statins, typically goes through a cyclical history, with initial use for several years in another disease setting, prior to epidemiological research identifying a possible chemo-protective effect. However, further information is required, including review of RCT data in the initial disease setting with exploration of cancer outcomes. Additionally, more contemporary methods should be considered, such as Mendelian randomization and pharmaco-epidemiological research with "target" trial design emulation using electronic health records. Pre-clinical and traditional observational data potentially support the role of statins in the treatment of cancer; however, randomised trial evidence is not supportive. Evaluation of contemporary methods provides little added support for the use of statin therapy in cancer. We provide complementary evidence of alternative study designs to enable a robust critical appraisal from a number of sources of the go/no-go decision for a prospective phase III RCT of statins in the treatment of cancer.

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Rothia mucilaginosa: a case of septic arthritis in a native knee and review of the literature (2021)

Type of publication:
Journal article

Author(s):
*Daoub, Ahmed; *Ansari, Hamza; *Orfanos, George; *Barnett, Andrew

Citation:
BMJ case reports; Jan 2021; vol. 14 (no. 1)

Abstract:
Rothia mucilaginosa is a Gram-positive aerobic coccus usually found in the oral and respiratory tract. Septic arthritis is an uncommon condition, but is an orthopaedic emergency. A rare case of knee septic arthritis due to R. mucilaginosa is presented. Patient management and outcomes are discussed, and learning points from this case are outlined to help manage any further cases that may arise.

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The correlation between bowel complications and cardiac surgery (2021)

Type of publication:
Journal article

Author(s):
Mishra V.; Hewage S.; *Islam S.; Harky A.

Citation:
Scandinavian Journal of Surgery; Jun 2021; vol. 110 (no. 2); p. 187-192

Abstract:
Although advances in knowledge and technology have improved outcomes in surgical cardiac patients over the last decade, complications following cardiac operations still remain to be potentially fatal. Gastrointestinal complications, in particular, tend to have high rates of reintervention and mortality following cardiac surgery, with ischemia and hemorrhage being two of the commonest underlying causes. The intention of this review is to identify which risk factors play important roles in predisposing patients to such complications and to gain better insight into the pathogenesis of the sequelae. Furthermore, strategies for prevention have been discussed to educate and increase awareness of how adverse cardiac surgical outcomes can be minimized.

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