Distal urethral carcinoma: Contemporary management with phallus preserving techniques.

INTRODUCTION: Primary urethral carcinoma is a rare clinical entity with an incidence of 1 case per million in the United Kingdom. Cancers of the distal urethra are most commonly of squamous subtype and often associated with Human Papilloma Virus infection. Penile preserving techniques are recommended in tumours of the pendulous urethra with a number of surgical approaches described. Herein, we describe the surgical management of 7 patients presenting with primary urethral carcinoma. METHODS: Seven patients diagnosed with primary urethral carcinoma of the distal urethra were identified using a prospectively maintained penile cancer database at our institution from May 2017 to November 2020. RESULTS: The mean age at presentation was 56.5 (33-80) years. Presenting symptoms included visible lesion, LUTS and a groin mass. Three patients had lesions located within the glanular urethra and had a distal urethrectomy and primary closure. Two patients with lesions extending proximal to the glanular urethra and into or beyond the fossa navicularis had a distal urethrectomy with a hypospadic neomeatus formation. One patient with tumour extending into the glans penis underwent distal urethrectomy and partial glansectomy with split thickness skin graft. A partial penectomy was performed for one patient with urethral tumour invading the corporal heads. Mean follow-up was 23.4 (±17.0) months. There have been no disease recurrences to date. CONCLUSION: Penile preserving techniques are feasible in patients with tumours of the pendulous urethra and do not appear to compromise local control.

Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.

Aim Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood. We present the case of a late relapse of RMS to the leptomeninges after 15 years. Methods A 20 year old male presented with a 3 week history of headaches and nausea. He previously had RMS of his right ear diagnosed at age 5 years which was treated with concurrent chemoradiotherapy. An MRI Brain and Spine confirmed extensive leptomeningeal disease and CSF analysis confirmed the presence of recurrent embryonal RMS. Results He completed two cycles of cyclophosphamide and topotecan followed by 45Gy/25Fr of craniospinal radiotherapy. Conclusion Late relapses beyond five years can be seen in up to 9% of patients, however very late recurrences (>10 years) are exceedingly rare. Molecular based methods such as gene expression profiling can aid risk stratification and survivorship clinics may become increasingly useful in following patients with high risk features.

The Early Impact of COVID-19 on Urological Service Provision.

Aim COVID-19 has posed an unprecedented challenge to healthcare systems. We aimed to observe the impact on urological care delivery in an Irish university hospital. Methods Data on urological activity was prospectively collected for 3 months from March 2020. A retrospective review of the same period in 2019 was performed for control data. Results Over the 2020 study period, 356 urological admissions were recorded; a 23.1% decrease from the 2019 corresponding period(n=463). A 21.7% decrease in flexible cystoscopies was seen (162 versus 207). 125 theatre cases (36 off-site) were performed in the 2020 period, versus 151 in 2019. Emergency case load remained stable, with 69 cases in the 2020 period. The percentage of trainee-performed cases was preserved. COVID-era outpatient activity increased, to involve 559 clinic consultations compared to 439 the preceding year; a reflection of annual growth in service demand and facilitated by virtual clinic application (n=403). There were 490 instances of patients cancelling/failing to attend outpatient appointments, compared to 335 in 2019. Conclusion The Irish COVID-19 outbreak has created obstacles for urological care. Nonetheless, urgent/emergent urological cases persist. Our unit has managed this to-date with flexible adaptation of service delivery. The global challenge posed by COVID-19 will demand ongoing resourcefulness to minimise impact on patients with time-sensitive urological conditions.

The Hidden Burden of Outpatient Repeat PSA Testing in a Prospective Cohort.

PSA testing is widespread throughout Europe for diagnostic purposes and follow up. We performed a prospective outpatient cohort study of 250 men (2013-2015) in two hospital sites. Included were those men being followed up by urology with PSA blood testing. First appointments and those men in whom non-PSA tests were ordered by urology were excluded. The median age was 67.2yrs (46-88). Eighty-one point two percent of samples had a combination of 21 different serology tests at an added cost of >€18,000. Abnormal serology resulted in 53 referrals. Twenty-six-six percent of correspondence referenced abnormal serology other than PSA. Follow up of non-PSA test results poses a challenge in an outpatient setting with failure to appropriately follow-up on abnormal results, increased costs, and medico-legal implications. There is currently no Irish legislature in place to safeguard hospital physicians. This study quantifies the levels of expenditure, resources and risk associated with ambulant PSA testing.

Proton therapy in paediatric oncology: an Irish perspective.

BACKGROUND: Proton therapy (PT) is a radiotherapy treatment modality that uses protons, rather than conventional photons. PT is often used in paediatric oncology due to its reported capability to reduce acute and late adverse treatment effects. As PT is unavailable in Ireland, patients are referred abroad for treatment. AIMS: To: (1) produce a descriptive study of Irish children referred abroad for PT, and (2) discuss the case for PT in general. METHODS: A retrospective review of all children referred for PT before October 2015 was performed. Information was gathered regarding demographics, diagnosis, referral timeline, adverse effects attributable to PT, current status and cost. A review of the relevant literature was performed. RESULTS: Seventeen children treated in Ireland have been referred abroad for PT. The largest number was in the 0-4 year old group. At initial diagnosis the median age was 4.8 years. The average cost per child was €37,312. Two patients suffered disease relapse. Four have encountered PT-related adverse effects. CONCLUSION: Despite the fact that >100,000 patients worldwide have been treated with PT, the level of published evidence to support superiority over conventional treatment remains low. It is debated that randomised control trials in this area would be inconsistent with the principle of clinical equipoise. In contrast, there is a call for level 1 evidence to justify drastic changes in patient care, particularly in light of recent reports of unexpected toxicities. In time, careful evaluation, follow-up and clinical trials will likely support the preferential use of PT in children.

Single centre experience of hypothermic machine perfusion of kidneys from extended criteria deceased heart-beating donors: a comparative study.

INTRODUCTION: Kidneys from extended criteria donors are associated with higher rates of delayed graft function (DGF). Hypothermic machine perfusion (MP) for storage is associated with more favourable outcomes. METHODS: A retrospective analysis was performed in 93 patients where the kidney was stored using hypothermic MP (LifePort(®)) and compared to an age-matched control group where the kidney was stored in cold static storage (CSS) using University of Wisconsin solution. RESULTS: Median age was similar in both groups (59.2 years in MP vs 59.9 years in CSS, p = 0.5598). Mean cold storage time was 15.6 h in MP vs 17.9 h in CSS. Post transplant mean serum creatinine was as follows; MP group-144.7 µmol/L at 1 month; 138.3 µmol/L at 3 months and 129.5 µmol/L at 12 months. In the CSS group-163 µmol/L at 1 month; 154.9 µmol/L at 3 months and 140.2 µmol/L at 12 months. There was a statistically significant difference at 1 month (p = 0.0096) and 3 months (p = 0.0236). DGF was defined as the need for haemodialysis within 7 days post transplant. In the MP group, DGF occurred in 17.2 % patients with mean of 6 days (range 1-18). In the CSS group, 25.8 % patients with mean of 8.1 days (range 3-25). One-year graft survival rate was better in the MP group (97.85 vs 96.77 %). CONCLUSION: Our experience to date recommends the use of hypothermic MP for storage of kidneys from extended criteria deceased heart-beating donors.

A single centre experience of active surveillance as management strategy for low-risk prostate cancer in Ireland.

INTRODUCTION: Active surveillance (AS) is a management strategy for addressing the widely acknowledged problem of over diagnosis and over treatment of clinically indolent prostate cancer. METHODS: A total of 80 patients were enrolled on the AS program in our institution between January 2008 and June 2012. All data were collected prospectively in a secure database. RESULTS: The mean age of patients enrolled was 62.7 years (range 50-72). Median PSA at enrolment was 5.6 ng/mL (range 1.2-13.4). The mean follow-up was 32 months (range 2-54). In total, 85 % of patients had a repeat biopsy after 1-year with 30 % having another biopsy after 3 years. Overall, 45 % of patients remain on AS. In the remainder; 42.5 % of patients have been removed from AS for definitive treatment, while 8.75 % of patients are now on watchful waiting, 2.5 % of patients self discharged from the program and one patient died of cardiovascular disease. The prostate cancer specific survival rate is 100 %. Reasons for removal from AS and referral for treatment were; 67.6 % of patients had upgrade of disease on repeat biopsy, 17.6 % of patients had PSA progression, 11.8 % patients had progression of disease on MRI, and one patient developed a palpable nodule. Regarding definitive treatment; 52.9 % of patients have been for referred for external beam radiotherapy, 14.7 % have been referred for brachytherapy, 29.4 % have been referred for surgery and one patient has refused definitive treatment. CONCLUSION: Our findings to date support active surveillance as a valid strategy for early, localised prostate cancer.

Nodal presentation of seminoma.

We report a 38 year old male with metastatic seminoma in an inguinal lymph node and regression of the primary testis tumour with a past history of orchiopexy--an extremely rare occurrence.

Successful outcome of patients with relapsed/refractor Hodgkin lymphoma treated with high dose chemotherapy at the National Adult Bone Marrow Transplant Unit at St. James's Hospital.

Patients with Hodgkin lymphoma who relapse or are refractory to first line multi-agent chemotherapy can be successfully salvaged with high dose therapy (HDT) and autologous stem cell transplant (ASCT). Twenty-six patients with relapsed or refractory Hodgkin lymphoma have been treated with HDT and ASCT at St James Hospital between 2000 and 2005. At day 100 post HDT-ASCT, 23 patients were in complete remission. This group included all 6 patients transplanted at first relapse, 8 of 9 with advanced disease and 9 of 11 with primary refractory disease. Patients treated in first relapse had the best outcome with an overall and progression free survival of 100% (median, 37 months). Patients with primary refractory disease had the poorest outcome with an overall survival of 76% (median, 28 months). All patients with primary refractory disease responsive to salvage chemotherapy were in remission at a median of 28 months. The presence of chemosensitive disease prior to transplantation was the most important determinant of outcome. PET-CT imaging is useful to assess chemosensititvity prior to HDT and thus predict which patients will do well post HDT-ASCT. No patient died of treatment related toxicity. The outcome of this patient series compares favourably with international figures.

Management of gastric lymphoma.

INTRODUCTION: The management of gastric lymphoma is controversial and a wide variety of unimodality or multimodality approaches have been used. The aim of this report is to highlight the variety of treatment regimens deployed, the outcomes achieved and to present a modern management approach for this enigmatic tumour. RESULTS: 42 cases of primary gastric lymphoma managed at one centre over a 15-year period were reviewed. Weight loss (52%), pain (41%) and anorexia (33%) were the most common presenting symptoms. Most patients (86%) had high-grade lymphoma. Primary treatment modalities included surgery (36%), chemotherapy (40%), supportive care only (22%) and H. pylori eradication (2%). Adjuvant therapies included chemotherapy (17%), radiotherapy (7%) and combined chemoradiotherapy (5%). The overall median survival was 53 months, with a five year survival of 46%. In the curative group, the median survival was 75 months and five year survival 58%. Curative surgery or chemotherapy +/- radiotherapy were similarly effective for stage IE and IIE disease. CONCLUSIONS: The prognosis for gastric lymphoma is grade- and stage-dependent. With equivalent outcomes for cure in localised gastric lymphoma for surgery and chemotherapy, the latter is preferred in this unit because of gastric preservation, with surgery being reserved for failed medical management or presentations with haemorrhage, perforation or obstruction refractive to steroid therapy.

Lifestyle and health behaviours of adults with an intellectual disability.

BACKGROUND: There is currently no published research in Ireland on the health behaviours of adults with an intellectual disability (ID). With an increasing age profile and similar patterns of morbidity to the general population, the ID population would benefit from baseline data from which to establish risk factors. METHODS: A questionnaire survey was carried out with 157 carers of people with an ID in the west of Ireland. RESULTS: The results of this survey were compared with results of a health survey for the general population in the same region. The present survey found that 68% of the ID sample was overweight or obese. Levels of smoking (2.6%) and regular alcohol consumption (10.3%) were relatively low in comparison with the general population. However, participation in exercise and adherence to a healthy diet were poor. The level of resident choice and decision-making did not have any relationship to health behaviours nor did residential setting. Finally, there were no gender differences in health and lifestyle profiles. CONCLUSION: The results of this study have important implications for health promotion interventions for people with an ID.

Relapsing granulomatous angiitis of the central nervous system in a patient while in remission from Hodgkin lymphoma.

We present a patient with granulomatous angiitis of the central nervous system (GANS) and Hodgkin lymphoma. His GANS resolved with treatment for the lymphoma, but then reactivated six months later in the absence of activate lymphoma. He made a full neurological recovery after treatment with reducing oral prednisolone over one year. This case indicates that prolonged use of steroids may be necessary to treat GANS in this setting and that it can run a course independent of the Hodgkin lymphoma.

Survival and progression in high grade tumour subset of G2 and G3 pT1 bladder transitional cell carcinoma.

AIMS: The newer 1998 WHO/ISUP grading system for bladder transitional cell carcinoma combined grade 3 (G3) and high grade tumour subset of grade 2 (G2) of the older 1973 WHO grading system into one homogenous high grade group. We evaluated for possible differences in survival and progression between these 2 grades in pT1 bladder tumours. METHODS: From Jan 1(st) 1991-Dec 31(st) 2003, 105 (61 G2 and 44 G3) pT1 bladder tumours fulfilled the 1998 WHO/ISUP high grade criteria. Survival and progression of these tumours were assessed. RESULTS: Of the 44 patients with G3 tumours, 20 are alive versus 22 of the 61 patients with high grade tumour subset of G2 (P=0.04). Of the 44 patients with G3 tumours, 13 progressed versus 12 of the 61 patients with high grade tumour subset of G2 (P=0.02). In multivariate analysis, G3 was a significant predictor of tumour progression (P=0.05) and marginally non-significant predictor of poor patient survival (P=0.056). CONCLUSIONS: A notable difference in survival and progression between high grade tumour subset of G2 and G3 is observed.

Elevated G2 chromosomal radiosensitivity in Irish breast cancer patients: a comparison with other studies.

Previous studies have shown that a significant proportion of breast cancer patients exhibit elevated G2 chromosomal radiosensitivity in contrast to controls (approximately 40%). In this study, the G2 assay was applied to a small number of Irish breast cancer patients who were recorded as sporadic cases and they were compared with a control group to compare and contrast with the previous documented studies. Lymphocyte cultures were set up on whole blood samples and stimulated with phytohaemagglutinin. The cultures were irradiated 74 h later with 0.5 Gy gamma-radiation and cells were arrested in metaphase by treating the cultures with colcemid. The chromosomes were harvested and the aberrations scored per 100 metaphases to assign a G2 score. The assay was first carried out on four donor controls to estimate intra-individual variation and then ten controls for inter-individual variation to measure assay reproducibility. The G2 assay was then applied to 27 breast cancer patients. Good intrinsic assay reproducibility was observed in the coefficient of variation (CV) data in three out of four controls. Intra-individual variation was similar in three out of four of the donors (4.6 - 5.1%) with one donor showing a higher CV compared with the others (22.9%). Inter-individual variation was calculated at 30.5% for all controls. No significant difference was observed between intra- and inter-individual variation using the variance ratio F-test. A G2 radiosensitivity cut-off of 110 aberrations/100 metaphases was calculated from the controls, and from this 70.4% of breast cancer patients and 7.7% of controls were calculated as G2 radiosensitive. This proportion of G2-sensitive breast cancer patients is the highest recorded in studies to date. It is thought that the G2 radiosensitivity assay is a biomarker of breast cancer predisposition genes of low penetrance, suggesting the presence of these genes in the Irish breast cancer patients used in this study who were recorded as sporadic cases. A larger number of Irish patients would be required to consolidate these findings and be representative of the Irish breast cancer population.

Somatic mutations of KIT in familial testicular germ cell tumours.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.