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Background Lymph node metastasis is the main determinant of survival in penile cancer patients. Conventionally clinical palpability is used to stratify patients to Inguinal Lymph node dissection (ILND) if clinically node positive (cN +) or Dynamic sentinel node biopsy (DSNB) if clinically node negative (cN0). Studies suggest a false negative rate (FNR) of around 10% (5–13%) for DSNB. To our knowledge there are no studies reporting harder end point of survival and outcomes of all clinically node positive (cN +) patients. We present our outcome data of all patients with penile cancer including false negative rates and survival in both DSNB and ILND groups. Methods One hundred fifty-eight consecutive patients (316 inguinal basins), who had lymph node surgery for penile cancer in a tertiary referral centre from Jan 2008 to 2018, were included in the study. All patients underwent ultrasound (US) ± fine needle aspiration cytology (FNAC) and then MRI/ CT, if needed, to stage their disease. We used combined clinical and radiological criteria (node size, architecture loss, irregular margins) to stratify patients to DSNB vs ILND as opposed to clinical palpability alone. Results 11.2% i.e., 27/241 inguinal basins had lymph node positive disease by DSNB. 54.9% i.e., 39/71 inguinal basins (IBs) had lymph node-positive disease by ILND. 4 inguinal basins with no tracer uptake in sentinel node scans are being monitored at patient’s request and have not had any recurrences to date. With a mean follow-up of 65 months (range 24–150), the false-negative rate (FNR) for DSNB is 0%. Judicious uses of cross-sectional imaging necessitated ILND in 2 inguinal basins with non-palpable nodes and negative US with false positive rate of 6.3% (2/32) for ILND. The same cohort of DSNB patients might have had 11.1% (3/27) FNR if only palpability criteria was used. 43 (28%) patients who did require cross sectional imaging as per our criteria had a low node positive rate of 4.7% ( p  = 0.03). Mean cancer specific survival of all node-positive patients was 105 months. Conclusion The performance of DSNB improved with enhanced radiological stratification of patients to either DSNB or ILND. We for the first time report the comprehensive outcome of all lymph node staging procedures in penile cancer.

The Warburg effect in tumour cells is associated with the upregulation of glycolysis to generate ATP, even under normoxic conditions and the presence of fully functioning mitochondria. However, scientific advances made over the past 15 years have reformed this perspective, demonstrating the importance of oxidative phosphorylation (OXPHOS) as well as glycolysis in malignant cells. The metabolic phenotypes in melanoma display heterogeneic dynamism (metabolic plasticity) between glycolysis and OXPHOS, conferring a survival advantage to adapt to harsh conditions and pathways of chemoresistance. Furthermore, the simultaneous upregulation of both OXPHOS and glycolysis (metabolic symbiosis) has been shown to be vital for melanoma progression. The tumour microenvironment (TME) has an essential supporting role in promoting progression, invasion and metastasis of melanoma. Mesenchymal stromal cells (MSCs) in the TME show a symbiotic relationship with melanoma, protecting tumour cells from apoptosis and conferring chemoresistance. With the significant role of OXPHOS in metabolic plasticity and symbiosis, our review outlines how mitochondrial transfer from MSCs to melanoma tumour cells plays a key role in melanoma progression and is the mechanism by which melanoma cells regain OXPHOS capacity even in the presence of mitochondrial mutations. The studies outlined in this review indicate that targeting mitochondrial trafficking is a potential novel therapeutic approach for this highly refractory disease.

IntroductionProgress in the knowledge of metabolic interactions between cancer and its microenvironment is ongoing and may lead to novel therapeutic approaches. Until recently, melanoma was considered a glycolytic tumour due to mutations in mitochondrial-DNA, however, these malignant cells can regain OXPHOS capacity via the transfer of mitochondrial-DNA, a process that supports their proliferation in-vitro and in-vivo. Here we study how melanoma cells acquire mitochondria and how this process is facilitated from the tumour microenvironment.MethodsPrimary melanoma cells, and MSCs derived from patients were obtained. Genes’ expression and DNA quantification was analysed using Real-time PCR. MSC migration, melanoma proliferation and tumour volume, in a xenograft subcutaneous mouse model, were monitored through bioluminescent live animal imaging.ResultsHuman melanoma cells attract bone marrow-derived stromal cells (MSCs) to the primary tumour site where they stimulate mitochondrial biogenesis in the MSCs through upregulation of PGC1a. Mitochondria are transferred to the melanoma cells via direct contact with the MSCs. Moreover, inhibition of MSC-derived PGC1a was able to prevent mitochondrial transfer and improve NSG melanoma mouse tumour burden.ConclusionMSC mitochondrial biogenesis stimulated by melanoma cells is prerequisite for mitochondrial transfer and subsequent tumour growth, where targeting this pathway may provide an effective novel therapeutic approach in melanoma.

Introduction Despite trauma accounting 9% of global mortality, it has been demonstrated that undergraduate trauma teaching is inadequate nationally and worldwide. With COVID-19 exacerbating this situation, a scalable, accessible, and cost-effective undergraduate trauma teaching is required. Methods Our Continual Professional Development United Kingdom (CPUDK)-accredited University Hospitals Birmingham (UHB) Major Trauma Service (MTS) affiliated programme consisted of seven biweekly pre-recorded sessions that were delivered online through the Moodle educational platform to University of Birmingham students. Pre- and post-randomised session-specific multiple-choice questions (MCQs) and anonymous feedback forms were administered. Results There were 489 student responses, with 63 students completing all seven sessions. On an 8-point scale, students’ objective knowledge scores increased by a mean of 1.2 ( p  < 0.001). Using a 5-point Likert scale, students also showed improvement in subjective outcomes including their confidence in assessing trauma patient (absolute difference (AD) 1.38, p  < 0.001), advising initial investigations and formulating initial management plans (AD 1.78, p  < 0.001) and thereby their confidence to manage a trauma patient overall (AD 1.98, p  < 0.001). A total of 410 student responses endorsed the online delivery of SATMAS through Moodle and recommended SATMAS to future medical students. Conclusion SATMAS has demonstrated positive student feedback and extensive recruitment from only one centre, demonstrating that our programme can be an indispensable low-cost learning resource that prepares undergraduate medical students for their trauma exams and informs the implementation of clinical skills required by all doctors. We publish our pilot study findings to encourage similar teaching programmes to be adopted at other universities nationally and internationally, to synergistically benefit students, tutors, and ultimately patients, on a larger scale.

Despite the shift towards consultant-led care, many patients with trauma are still seen by junior doctors. Previous research has demonstrated that junior doctors feel unprepared to work in acute care but there is a paucity of recent research in trauma specifically. Thus, a national study is required to investigate the current state of undergraduate trauma teaching and identify specific areas for improvement. Between August and September 2020, a 35-item structured questionnaire was distributed among doctors who graduated from UK medical schools within the last 4 years. The questionnaire retrospectively assessed their experience of trauma teaching at medical school and their confidence to diagnose and manage patients with trauma. 398 responses were recorded from graduates of 39 UK medical schools. With 79.6% reporting only 0-5 hours of bedside trauma teaching and 51.8% reporting less than 20 hours in Accident and Emergency, graduates reported that trauma teaching was deficient compared with other specialties (78.1%). The majority of graduates were not confident in the initial assessment (72.9%) of a patient with trauma and almost all felt that a short course in trauma would be useful (93.7%). 77.4% of students felt that online learning would be beneficial and 92.9% felt that simulation would be useful. There is lack of standardised undergraduate trauma teaching nationally; a formal undergraduate teaching to ensure that new graduates are competent in the management of trauma would be supported by students. It is likely that a blended learning approach, incorporating e-learning with traditional teaching and clinical experience would be well received.