Recent Submissions

  • Multidisciplinary team approach in breast cancer care: Benefits and challenges

    Blackwood, Owain (Indian Journal of Pathology & Microbiology, 2020-02)
    The multidisciplinary team approach has been employed internationally for decades, as an attempt to bring collaborative decision-making and concentrate clinical experience from multiple specialties on single patient cases in a systematic fashion. Adoption is not yet worldwide, but is increasing. The role of the histopathologist is central, providing vital information and context to clinical diagnosis and management. Our review summarizes some of the most relevant research on the topic of MDT usage and efficacy in relation to breast cancer, attempting to draw together its advantages and challenges. It is hoped that this review will make a contribution to the current international literature regarding multidisciplinary approaches in breast cancer care. Competing Interests: None
  • Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study.

    Downer, Nicola (BMJ Open Respiratory Research, 2023-11)
    Introduction: Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time. Methods and analysis: STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I-III lung cancer, (2) mini-PE, (3) Performance Status 0-2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023.
  • Case 11-2023: A Man with Mantle-Cell Lymphoma and Hypoxemia.

    Gupta, Anindya (NEJM, 2023-07)
    To the Editor: Schmidt and colleagues (April 13 issue)1 provide a logical rationale for administering methylene blue therapy in a patient with hypoxemia caused by dapsone-induced methemoglobinemia. It is important to consider testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency before administering methylene blue therapy, particularly in the context of possible dapsone-induced hemolytic anemia. Methylene blue would be ineffective for the treatment of methemoglobinemia in a patient with G6PD deficiency2,3 because the drug requires a reduction to leukomethylene blue by NADPH,4 which is depleted in patients with G6PD deficiency. Furthermore, methylene blue — an oxidant — may paradoxically precipitate hemolysis in G6PD-deficient . . .
  • Predictors of Hypersensitivity Reactions to Platinum-Based Chemotherapy in a Tertiary Care Hospital in Oman: A case control study.

    Abdullah, Eman (Sultan Qaboos University Medical Journal, 2023-05)
    Objectives This study aimed to estimate the prevalence and evaluate risk factors of hypersensitivity reactions (HSRs) to platinum-based compounds (PBCs) in cancer patients. PBCs play an important role in cancer therapy. However, one of the drawbacks of PBCs is the occasional occurrence of HSRs, which can lead to serious consequences. Methods This retrospective case control study was conducted from January 2013 to December 2020 at Sultan Qaboos University Hospital, Muscat, Oman and included patients who received any PBC for the management of non-haematological cancers. Data regarding demographic characteristics and diseases and treatment details were collected from the hospital’s electronic database. The data were quantitatively described and Student’s t-test and Wilcoxon Mann-Whitney tests were used to detect significant differences. Results A total of 38 cases and 148 matched controls were studied. The prevalence of HSRs to PBCs in the cohort of this study was 4.7% (95% confidence interval: 3.33–6.37%), higher with carboplatin compared with cisplatin and oxaliplatin. The female gender (P = 0.032), concomitant taxanes (P = 0.002) and concurrent radiation (P <0.001) were significant predictors of HSRs to PBCs. The majority of the reactions were of mild to moderate severity, and the rechallenge rate after HSR development was 13%. Conclusion HSRs to PBCs impact therapy decisions and understanding the risk factors is important to improve treatment outcomes in cancer patients.
  • Oncoplastic breast surgery in older women with primary breast cancer: a systematic review

    Chia, Zoe
    Background: Oncoplastic procedures allow excision of larger breast tumours, or unfavourable tumour/breast ratio lesions while achieving a good cosmetic outcome. This increases the pool of patients eligible for breast conservation over mastectomy, reducing the need for more extensive surgery in older women and potentially improving their quality of life. Nonetheless, studies to date suggest a poor uptake of oncoplastic breast surgery in the older group. This review aimed to establish whether a disparity in uptake of oncoplastic breast surgery exists between older and younger women, and to explore the underlying reasons for this. Methods: A literature search was conducted on 17 January 2022 using MEDLINE and Embase. Eligible studies comprised full-text articles of patients who underwent oncoplastic breast surgery for primary invasive breast cancer, and included those aged at least 65 years. Results: Ten published studies were identified. One study was ranked as providing level 2 evidence, and the remainder were level 3. A total of 567 women underwent oncoplastic breast surgery for primary breast cancer, of whom only 61 (10.8 per cent) were aged 65 years or older. None of the studies directly compared younger with older women, or explored the underlying factors contributing to this discrepancy in uptake. Conclusion: This review has demonstrated a lower uptake of oncoplastic breast surgery in older compared with younger women. Given the increasing number of older women living with breast cancer who may be eligible for breast-conserving surgery, further research into this area is required.
  • CT-derived measures of muscle quantity and quality predict poorer outcomes from elective colorectal surgery: a UK multicentre retrospective cohort study.

    Boyd-Carson, H
    Purpose: To assess whether preoperative radiologically defined lean muscle measures are associated with adverse clinical outcomes in patients undergoing elective surgery for colorectal cancer. Methods: This retrospective UK-based multicentre data collection study identified patients having had colorectal cancer resection with curative intent between January 2013 to December 2016. Preoperative computed-tomography (CT) scans were used to measure psoas muscle characteristics. Clinical records provided postoperative morbidity and mortality data. Results: This study included 1122 patients. The cohort was separated into a combined group (patients with both sarcopenia and myosteatosis) and others group (either sarcopenia or myosteatosis, or neither). For the combined group, anastomotic leak was predicted on univariate (OR 4.1, 95% CI 1.43-11.79; p = 0.009) and multivariate analysis (OR 4.37, 95% CI 1.41-13.53; p = 0.01). Also for the combined group, mortality (up to 5 years postoperatively) was predicted on univariate (HR 2.41, 95% CI 1.64-3.52; p < 0.001) and multivariate analysis (HR 1.93, 95% CI 1.28-2.89; p = 0.002). A strong correlation exists between freehand-drawn region of interest-derived psoas density measurement and using the ellipse tool (R2 = 81%; p < 0.001). Conclusion: Measures of lean muscle quality and quantity, which predict important clinical outcomes, can be quickly and easily taken from routine preoperative imaging in patients being considered for colorectal cancer surgery. As poor muscle mass and quality are again shown to predict poorer clinical outcomes, these should be proactively targeted within prehabilitation, perioperative and rehabilitation phases to minimise negative impact of these pathological states.
  • Surgical outcomes following one stage partial breast reconstruction with chest wall perforator flaps

    Dube, Manas; Puthu, Dev (EJSO, 2023-05)
    Introduction: In the last two decades, pedicled chest wall perforator flaps (CWPF) have become a versatile tissue replacement technique for partial breast reconstruction following breast-conserving surgery in well-selected cases. We present the surgical outcomes of our eighty patients with chest wall perforator flap based one stage partial breast reconstructions.
  • Predictors of surgical site infection following breast surgery

    Dube, Manas; Puthu, Dev; Tehniyat, Wajiha (EJSO, 2023-05)
    Introduction: Surgical site infection (SSI) is common after breast surgery despite being clean surgery. Several works of literature reported SSI rates between 3-15%. Co-morbidities like diabetes, obesity and smoking are known risk factors however, using traditional risk factors it may not always be possible to identify the patients who are at risk of SSI. We endeavoured to assess the usefulness of the American College of Surgeons' Surgical Risk Calculator (ACS-SRC) in predicting SSI following breast surgery.
  • Value of Drains in Soft-Tissue Tumour Surgery: A Specialist Regional Centre Experience

    Akbari, Amir R (Cureus, 2022-12)
    Background The mainstay of therapy in most soft-tissue tumours (STTs) is excision. However, this often results in blood/extracellular fluid collection within large dead spaces necessitating the use of surgical drains. Whether meticulous attention to haemostasis, careful closure of dead space, and use of compression bandage obviates the need for drains was investigated. This study aimed to compare postoperative outcomes in patients undergoing surgery for STTs with and without the use of drains. Methodology A retrospective analysis of patients undergoing STT surgery over five years was undertaken using a regional STT specialist service database. Patients were stratified into the following two groups: compression bandage alone (CB) versus compression bandage with drain (CBD). The chi-square test was used to examine associations with infection, seroma, and haematoma, while the unpaired t-test was used for associations with hospital stay and time to wound healing. The unpaired t-test with Bonferroni correction was used to account for tumour dimensions across both groups. Results A total of 81 CB and 25 CBD patients were included. The mean hospital stay was significantly lower in CB compared to CBD (4.9 days, SD = 8.574 vs. 9.8 days, SD = 7.647, p = 0.0125). None of the other variables was significantly different between the two groups, including infection (21.3% vs. 24.0%, p = 0.7804), seroma (25.0% vs. 36.0%, p = 0.2865), haematoma (0.026% vs. 2.0%, p = 0.2325), and time to wound healing (55.8 days, SD = 63.59 vs. 42.3 days, SD = 58.88, p = 0.3648). Conclusions Our findings suggest that the use of drains in patients undergoing STT tumour surgery lengthens hospital stay without reducing the incidence of postoperative complications/time to wound healing. A larger, prospective trial is needed.
  • Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial

    Geary, S
    The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. Method: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. Results: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. Conclusions: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy.
  • An inconvenient truth concerning surgery for mesothelioma.

    Roberts, Mark (Journal of Clinical Oncology, 2018-09)

    Smith, Susan; Jones, Steve (HemaSphere, 2022-06)
    Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/- R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/- R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively.
  • Antibiotic prophylaxis in breast surgery: a meta-analysis to identify the optimal strategy to reduce infection rates in breast surgery.

    Akbari, Amir R
    Intro: Breast surgeries are an increasingly frequent operation, with an exponential rise in breast cancer diagnoses, and women opting for cosmetic surgeries. SSIs are the most common post-operative complication with many negative consequences including sepsis and even death. These are treated with prophylactic antibiotics prior to surgery. Breast surgery is currently defined as 'clean', although literature indicates that the infection rate is higher than should be expected for this classification. The aim of this meta-analysis is to evaluate whether pre-operative antibiotics reduce SSI frequency and which class of antibiotics achieve the best reduction. Methods: A literature search through online libraries was used to find clinical trials investigating pre-breast-surgery antibiotics and SSI frequency. These were grouped all together and separately by class of antibiotics. Additionally studies investigating breast cancer surgeries and non-cancer surgeries were grouped separately. A forest-plot was created for each group to calculate an estimated effect, these were then compared against each other. Results: Use of antibiotics resulted in a reduction in SSI frequency by 3.55% overall, and reduced frequency in all types of surgeries performed. Cephalosporins reduced SSI frequency by 2.23%, Beta-lactamase inhibitors 4.17% and macrolides achieved the greatest effect with a 14.58% reduction. Conclusion: This meta-analysis proves that antibiotics reduce SSI frequency in breast surgery and supports the notion to remove the 'clean' classification. This definition may result in failure to provide prophylaxis, resulting in patients suffering from preventable SSIs and their negative consequences. Macrolides were the most effective followed by beta-lactamase inhibitors and cephalosporins, this may be implemented in structuring new guidelines favouring use of macrolides before conducting breast surgery.
  • eQTL set-based association analysis identifies novel susceptibility loci for Barrett's esophagus and esophageal adenocarcinoma

    Jankowski, Janusz
    Background: Over 20 susceptibility single-nucleotide polymorphisms (SNPs) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), explaining a small portion of heritability. Methods: Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTLs), and set-based SKAT association using selected eQTLs that predict the gene expression. Results: While the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641 and HSP90AA1). Conclusions: This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set based genetic association approach. Impact: This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set based genetic association approach as an alternative method for TWAS analysis.
  • Evaluation of a novel paper-based algorithm for breast family history risk assessment.

    Milburn, Nikki; Jahan, Ali; Elamin, Ghassan (EJSO: European Journal of Surgical Oncology, 2022-05)
  • Transforming the 2-week wait (2WW) pathway: management of breast pain in primary care.

    Jahan, Mohamed; Milburn, Nikki (BMJ Open Quality, 2022-03)
    Breast pain has no association with breast cancer yet is a frequent reason for referral from Primary to Secondary Care, often on an urgent (2-week wait) referral. The referral often causes significant patient anxiety, further heightened by screening mammograms and/or ultrasound scans in the absence of an associated red flag symptom or finding by the patient or general practitioner. This paper reports the pilot implementation of a specialist Primary Care Breast Pain Clinic in Mid-Nottinghamshire where patients were seen, examined without any imaging and assessed for their risk of familial breast cancer: numerous studies have reported 15%–>30% of patients with breast pain only have a family history of breast cancer. 177 patients with breast pain only were seen in this clinic between March, 2020 and April, 2021 with a 6-month interim suspension due to COVID-19. The mean age of patients was 48.4 years (range: 16–86). 172/177 (97.2%) patients required no imaging although there were three (1.7%) inappropriate referrals and two additional abnormalities (1.1%—hamartoma, thickening/tethering) that were referred onward. There were no cancers. 21 (12.4%) patients were identified to have an increased familial risk of breast cancer and were referred to the specialist familial cancer service. 170/177 patients completed an anonymous questionnaire on leaving the clinic. 167/169 (99%) were reassured regarding their breast pain, 155/156 (99%) were reassured of the Familial Risk Assessment, 162/168 (96%) were reassured regarding their personal risk assessment while 169/170 (99%) were ‘extremely likely/likely to recommend the service’. This specialist Primary Care Breast Pain Clinic provides service improvement across all levels of care (Primary, Secondary and Tertiary). Patients were successfully managed in the community with high levels of patient satisfaction and together this obviated referral to secondary care. The familial breast cancer risk assessment also helped identify unmet need in the community.
  • Incidental finding of prostate cancer in transurethral resection of prostate (TURP) specimens: A retrospective analysis from a tertiary care hospital in Pakistan

    Memon, Shahbaz Mustafa (The Pan African Medical Journal, 2021-05)
    Introduction: incidental prostate cancer findings reflect the great burden of prostatic cancer across the globe. Our 10 year retrospective analysis aimed to identify the incidence and clinic-pathologic features of prostate cancer incidentally detected in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH), and to estimate the clinical value of pathologic review of all TURP specimens. Methods: after excluding patients with a known diagnosis of prostate cancer prior to TURP a total of 2,386 men (ages 25-98) were identified by pathology (TURP) specimens. Yearly incidences, Gleason score, grade, pathologic stage were recorded for all incidental prostate cancer patients. Results: a total of 256 (10.7%) patients were found to have prostate cancer. Mean Age was 68.51±9.22 years. T1a and T1b stage prostatic carcinoma was found in 9.9% and 90.1% of these patients respectively. Forty-nine percent (49%) patients had higher Gleason scores (>7). After subtracting average incidences between 5-year intervals, a statistical rise of almost 4% was found. Conclusion: our analysis concludes that a large proportion (10.7%) of patients had incidental prostate cancer and the incidence was increasing in recent years in Pakistan and in comparison, to Asian countries. In Pakistan there is a scarcity of updated national cancer registries. The growing incidence of high Gleason scores requires keen and prompt attention. The diverse ethnic and socioeconomic background of patients propels their propensity towards loss of follow up with already limited tertiary healthcare institutes in Pakistan. This pathologic review of TURP specimens is valuable for Asiatic and non-Asiatic populations.
  • Parathyroid carcinoma presenting with ventricular bigeminy in pregnancy.

    Sivasankaran, Karthikeyan (BMJ Case Reports, 2022-02)
    Parathyroid carcinoma is very rare in pregnancy. Clinical features are similar to primary hyperparathyroidism. A 38-year-old pregnant woman had repeated hospital admissions for palpitations, headaches, dizziness and polydipsia. Blood investigations showed severe hypercalcaemia with raised parathyroid hormone and 24-hour ECG showed ventricular bigeminy and premature ventricular contractions. Neck ultrasound showed a lesion in the right thyroid lobe. Consequently, she underwent an en bloc resection of the right parathyroid and thyroid lobe at 23 weeks gestation. Histology results confirmed parathyroid cancer. This case highlights the complexities of identifying hypercalcaemia in pregnancy due to the overlapping features with common disorders of pregnancy. Early recognition and timely surgical management can prevent maternal and fetal complications. Also, the case demonstrates the value of interprofessional collaboration between different specialities in providing quality care and improving outcomes. An abridged version of this case was presented at European Congress of Endocrinology 2021.

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