The role of URO17® in diagnosis and follow up of bladder cancer patients.

OBJECTIVE: to evaluate the role of urinary URO17® biomarker in the detection of urothelial tumors in haematuria patients and the detection of recurrence in non-muscle invasive bladder urothelial tumors. MATERIALS AND METHODS: Our study was formed of two cohorts of patients, group I represents patients presenting with haematuria (n = 98), while group II represents patients with known non-muscle invasive bladder cancers on their scheduled follow up cystoscopic investigation (n = 51). For both groups, patients were asked to provide urine samples before cystoscopy, either primary as part of the haematuria investigation or as a scheduled follow-up. Urine samples were sent anonymously for standard urine cytology and URO17® biomarker immunostaining. Results were compared to cystoscopic findings using Chi-square analysis and Fisher's exact test (P < 0.05). RESULTS: Group I was formed of 98 patients, with an average age of 60 years. URO17® showed 100% sensitivity and 96.15% specificity with a negative predictive value (NPV) of 100 and a positive predictive value (PPV) of 95.83. The results showed statistical significance with P value < 0.001. Group II was formed of 51 patients, with an average age of 75 years. URO17® was shown to have a sensitivity of 85.71% and NPV of 95.45. Eleven patients of group II were on scheduled BacillusCalmette-Guerin (BCG) and another 5 received Mitomycin C (MMC). The overall results of both groups combined (n = 149) showed statistical significance between flexible cystoscopy results and the results of urinary URO17® and urine cytology. CONCLUSION: URO17® has a potential to be a reliable test for diagnosis and follow up of urothelial cancer patients and a screening tool adjunct to flexible cystoscopy. TRIAL REGISTRATION: Not applicable as the current study is not a clinical trial, as per according to the National Institutes of Health, "studies that involve a comparison of methods and that do not evaluate the effect of the interventions on the participant do not meet the NIH clinical trial definition."

Stage, grade and pathological characteristics of bladder cancer in the UK: British Association of Urological Surgeons (BAUS) urological tumour registry.

OBJECTIVE: To investigate Tumour-Node-Metastasis (TNM) stage and demographics at presentation in a very large, contemporary UK cohort of patients with bladder cancer and compare them with other published series, as little published data exists on the pathological characteristics of bladder cancer at presentation. PATIENTS AND METHODS: The British Association of Urological Surgeons (BAUS) Section of Oncology started a new urological tumour registry in 1998. We performed a data analysis of all bladder cancer cases between 1999 and 2008. Tumour TNM stage, grade and histopathological diagnosis were reviewed along with standard epidemiological data. RESULTS: In all, 69,712 bladder cancer registrations were recorded. Complete T, N and M stage and grade was available for 32,240 patients. The male to female ratio of the study population was 3:1 and the overall median (sd, range) age at presentation was 73 (11.6, 6-108) years. Final pathological T staging showed that non-muscle-invasive bladder cancer accounted for 75% of cases with the remaining 25% being muscle-invasive disease. Of these patients, 8% had nodal disease and 4% other metastatic sites at presentation. The tumour grade was G1-2 in 65% and G3 in 35% of cases. Transitional cell carcinoma (TCC) accounted for 92%, squamous cell carcinoma and adenocarcinomas 1.5% each, with 5% other histological variants. CONCLUSIONS: Non-muscle-invasive TCC accounted for 75% of bladder cancer cases in the UK. The 1973 World Health Organization classification remains in widespread use amongst pathologists in the UK. Obtaining complete and standardised staging and pathology reporting systems in bladder cancer remains a challenge.

Current practice for determining pulmonary capillary wedge pressure predisposes to serious errors in the classification of patients with pulmonary hypertension.

BACKGROUND: Accurate measurement of left ventricular filling pressure is important to distinguish between category 1 pulmonary arterial hypertension (PAH) and category 2 pulmonary hypertension (PH) from left heart diseases (PH-HFpEF). We hypothesized that the common practice of relying on the digitized mean pulmonary capillary wedge pressure (PCWP-digital) results in erroneous recordings, whereas end-expiratory PCWP measurements (PCWP-end Exp) provide a reliable surrogate measurement for end-expiratory left ventricular end-diastolic pressure (LVEDP-end Exp-end Exp). METHODS: We prospectively performed left and right cardiac catheterization on 61 patients referred for evaluation of PH and compared the LVEDP-end Exp to end-expiration to the (a) PCWP-end Exp and (b) PCWP-digital. RESULTS: The PCWP-end Exp was a more reliable reflection of LVEDP-end Exp (mean 13.2 mm Hg vs 12.4 mm Hg; P, nonsignificant) than PCWP-digital (mean 8.0 mm Hg vs 12.4 mm Hg, P < .05). Bland-Altman analysis of PCWP-digital and LVEDP-end Exp revealed a mean bias of -4.4 mm Hg with 95% limits of agreement of -11.3 to 2.5 mm Hg. Bland-Altman analysis of PCWP-end Exp and LVEDP-end Exp revealed a mean bias of 0.9 mm Hg with 95% limits of agreement of -5.2 to 6.9 mm Hg. If PCWP-digital were used to define LVEDP-end Exp, 14 (27%) of 52 patients would have been misclassified as having PAH rather than PH-HFpEF. Patients with obesity and hypoxia were particularly more likely to be misclassified as PAH instead of PH-HFpEF if PCWP-digital was used to define LVEDP-end Exp (odds ratio 8.1, 95% CI 1.644-40.04, P = .01). CONCLUSIONS: The common practice of using PCWP-digital instead of PCWP-end Exp results in a significant underestimation of LVEDP-end Exp. In our study, this translated to nearly 30% of patients being misclassified as having PAH rather than PH from HFpEF.

Wellens syndrome: a life-saving diagnosis.

The diagnosis of acute coronary syndrome relies on clinical history, electrocardiographic (ECG) changes, and cardiac biomarkers; but within the spectrum of acute coronary syndrome, there exist subtle presentations that cannot afford to be overlooked. Wellens syndrome is one such example, in which a patient can present with both ECG changes that are not classic for myocardial ischemia and negative cardiac biomarkers. The characteristic ECG findings associated with Wellens syndrome consist of deep, symmetric T-wave inversions in the anterior precordial leads. However, Wellens syndrome can also present as biphasic T-wave inversions in those same ECG leads. The associated critical stenosis of the proximal left anterior descending artery carries an immediately life-threatening prognosis if not recognized promptly (Am Heart J. 1982;103[4 Pt 2]:730-736). We describe a case of a less common manifestation of Wellens syndrome (type 1) followed by a discussion of its implications and management.

Primary squamous cell carcinoma of the testis: a rare presentation.

A man in his mid-70s presented with a lump in his left testicle. He had previously been treated for prostate cancer with radical radiotherapy. He was on treatment for hypertension and type 2 diabetes. An ultrasound of the testes demonstrated a solid intratesticular mass for which he underwent left orchidectomy. Histology from the orchidectomy was moderately differentiated squamous cell carcinoma (SCC), positive for cytokeratin (CK) 5/6 and p63. A positron emission tomogram (PET) scan was clear of any metastatic disease. His surveillance CT, done at 12 months, revealed mediastinal, abdominal and hilar adenopathy. Biopsy of hilar lymph nodes showed SCC and this was treated with platinum-based chemotherapy. Unfortunately, the patient died after 18 months. To our knowledge, this is the first reported case of metastatic SCC of testes with extensive spread and with platinum-refractory disease.

Giant Paratesticular Liposarcoma Mimicking a Left-Sided Groin Hernia: A Case Report.

Giant paratesticular liposarcoma (PLS) is an uncommon tumour, often misdiagnosed pre-operatively, which presents as a painless scrotal mass. Early detection and prompt surgical management provide the best outcome. We present an 87-year-old patient with gradually enlarging, painless left scrotal swelling. Ultrasound on initial presentation suggested a benign hernia, resulting in an 11-month treatment delay. Computed tomography (CT) thereafter showed paratesticular scrotal mass measuring 14 x 8 x 7cm. Radical inguinal orchidectomy with high ligation of the spermatic cord was performed. Histopathology and cytogenetics confirmed PLS with both de-differentiated and well-differentiated features involving the spermatic cord margin. The patient had rapid progression to fatal lung metastasis within three months of surgery. Our case highlights that any suspicious fat swelling should be investigated thoroughly and excised promptly if paratesticular liposarcoma is suspected, as delayed management gives poor outcomes.

Neurovascular structure-adjacent frozen-section examination robotic-assisted radical prostatectomy: outcomes from 500 consecutive cases in the UK.

The purpose is to report the United Kingdom's largest single-centre experience of robotically assisted laparoscopic radical prostatectomies (RALP), using the neurovascular structure-adjacent frozen-section (NeuroSAFE) technique. We describe the utilisation and outcomes of this technique. This is a retrospective study from 2012 to 2019 on 520 patients undergoing NeuroSAFE RALP at our Institution. Our Institution's database was analysed for false-positive frozen-section (FS) margins as confirmed on paraffin histopathological analysis: functional outcomes of potency, continence, and biochemical recurrence (BCR). The median (range) of console time was 145 (90-300) min. In our cohort, positive FS was seen in 30.7% (160/520) of patients, with a confirmatory paraffin analysis in 91.8% of our patients' cohort (147/160). The neurovascular bundles (NVBs) that underwent secondary resection contained tumour in 26.8% (43/160) of the cases. Biochemical recurrence (BCR) was 6.7% (35/520), of which FS was positive in 40% (14/35) of those cases. There were insufficient evidence of a statistical association of urinary incontinence and positive surgical margin rates according to NS or NVB resection. NeuroSAFE enables intraoperative confirmation of the oncologic safety of a NS procedure. Patients with a positive FS on NeuroSAFE can be converted to a negative surgical margin (NSM) by ipsilateral wide resection. This spared 1 in 4 men from positive margins posterolaterally in our series. Limitations are the absence of a matched contemporary cohort of NS RALP without NeuroSAFE in our centre.

The role of URO17™ biomarker to enhance diagnosis of urothelial cancer in new hematuria patients-First European Data.

Introduction and objectives: Novel biomarker research is vital for the progression of safe and thorough diagnostic medicine. There is now a need to improve the diagnosis of bladder cancer via a noninvasive urine test while balancing the risks of harm from investigational procedures, such as cystoscopy and radiological tests, against the likelihood of malignancy. We evaluate the diagnostic accuracy and sensitivity of Uro17™ urinary biomarker for the detection of urothelial cancer in hematuria patients in a prospective blinded validation study. Uro17™ is an immunobiomarker which binds to the oncoprotein Keratin 17, which is involved in the replication cycle of malignant cells. This study compared cystoscopic and histological investigations against Uro17™ results in patients being investigated for symptoms of urothelial cancer. Materials and methods: After receiving both local and national ethics/protocol approval, 71 patients were consented and recruited into the study. All patients were scheduled to undergo cystoscopic investigation, and following recruitment, a urine sample was collected. Urine samples were anonymized and processed as per standard cytology protocols and stained using Uro17™ immunobiomarker. The pathologists assessing the results were blinded to the patient and background history, and the results were compared to the biopsy histology. Results: The full cohort of enrolled patients consisted of 71 participants included. There were 55 males and 16 females, with an average age of 70. Thirteen were current smokers, 42 ex-smokers, and 16 nonsmokers. The malignancies detected included both muscle-invasive (n = 6) and non-muscle-invasive tumors (n = 38), and tumors of all grades and carcinoma in situ. Uro17™ was shown to have an overall sensitivity of 100% and a specificity of 92.6%, with a positive predictive value of 0.957 and negative predictive value of 1. Uro17™ investigation was positive in every case of urothelial malignancy. Conclusions: Our current data indicates Uro17™ is a highly sensitive noninvasive bladder cancer urine detection test that can improve the diagnosis of Bladder cancer. This can further improve diagnostic capabilities in primary care, reduce the number of referrals to Urology department, and reduce the number of unnecessary invasive procedures for new patients with a suspected urinary bladder cancer.

Sarcoid granulomas in the parathyroid gland - a case of dual pathology: hypercalcaemia due to a parathyroid adenoma and coexistent sarcoidosis with granulomas located within the parathyroid adenoma and thyroid gland.

We present a highly unusual and interesting case of coexistent hyperparathyroidism and sarcoidosis leading to hypercalcaemia. A 70 year old female presented with weight loss, constipation and dehydration. Investigations revealed marked hypercalcaemia with a non-suppressed PTH. In view of the degree of hypercalcaemia as well as the unintentional weight loss, investigations for malignancy were conducted -these were negative. Parathyroid imaging was then requested and an adenoma was identified. Surprisingly, surgery revealed the coexistence of a parathyroid adenoma with the unexpected finding of sarcoid granulomas within the parathyroid and thyroid glands. To our knowledge, this is the first such case reported. Further imaging confirmed pulmonary sarcoidosis and a serum ACE was elevated. Serum calcium levels did not respond to parathyroidectomy but eventually fell with steroid therapy.

Echocardiographic quantification of left ventricular mass: prognostic implications.

Left ventricular hypertrophy (LVH) has been shown to be an independent risk factor for adverse cardiac and cerebrovascular events. Despite this well-known association, the lack of a standardized approach for the quantification and the monitoring of LVH regression has limited its use as a primary risk factor that can be easily clinically targeted. Echocardiography has become the most widespread tool used for the quantification of LVH. With advances in this technology, echocardiographic quantification of LVH has improved and reference standards are being used to determine the clinical implications of LVH regression. In this article, we aim to provide a current appraisal of LVH with a focus on presenting the current clinical methods used to accurately detect LVH, the prognostic implications of these findings, and help develop a therapeutic target for clinicians.

Clinical methods for the detection and management of left ventricular hypertrophy.

Left ventricular hypertrophy (LVH) has been shown to be an independent risk factor for adverse cardiac and cerebrovascular events. Despite this well-known association, the lack of a standardized approach for both the quantification of LVH and the monitoring of LVH regression has limited its use as a primary risk factor that can be clinically targeted. In this State of the Art Paper, we will provide a current appraisal of LVH with a focus on presenting the current methods to accurately detect LVH and management strategies to develop a therapeutic target for clinicians.

Splenic marginal cell lymphoma (SMZL): report of its presentation with spontaneous rupture of the spleen.

Rupture of the spleen is a potentially life-threatening condition, which most often occurs secondary to abdominal trauma. Spontaneous rupture of the spleen is a much rarer event, usually occurring secondary to infections and less frequently secondary to haematological malignancies causing massive splenomegaly. We present a case of a 71-year-old woman who presented in the emergency department with acute abdominal and back pain and no history of trauma, with a CT scan diagnosis of splenic rupture. Splenectomy was performed and the histological examination of the specimen revealed splenic marginal cell lymphoma (SMZL), which is classified under the non-Hodgkins lymphomas (NHL) and accounts for <1% of NHL. There is only one previously reported case of spontaneous splenic rupture SMZL and this is the first recorded case of spontaneous splenic rupture in a patient without massive splenomegaly.

Acute myocardial infarction and cardiac arrest due to coronary artery perforation after mitral valve surgery: successful treatment with a covered stent.

We present a case of a gentleman who presented with acute myocardial infarction and cardiac arrest 6 days after undergoing mitral valve replacement surgery. Immediate coronary angiography revealed perforation of the left circumflex artery which was successfully treated with a covered stent. This report details the successful percutaneous treatment of an exceedingly rare complication of mitral valve surgery.

Interchangeability of activated clotting time values across different point-of-care systems.

Significant variability in activated clotting time (ACT) measurement exists based on the type of point-of-care system used. We sought to determine the degree of agreement in ACT measurements by the Hemochron Response and the Hemochron Signature Elite Whole Blood coagulation systems and whether these 2 systems can be used interchangeably. We prospectively compared 126-paired samples in 77 patients undergoing percutaneous coronary intervention. ACT was measured for each sample using the Hemochron Response system with glass test tubes and the Hemochron Signature Elite system with low-range ACT cuvettes simultaneously. We used correlation and Bland-Altman analyses. Mean age of the study cohort was 67 ± 11 years, 49% were women, and 65% of measurements were made after systemic anticoagulation. There was a significant correlation between the Hemochron Response and Hemochron Signature Elite systems (r = 0.84, p <0.01). However, the mean bias for the ACT measurement was 9 seconds (95% confidence interval -69 to 86). In the therapeutic range of ACT measurements, the mean bias was 15 seconds (95% confidence interval -60 to 91). Thirty-three percent of total samples had >10% disagreement and 8% of samples had >20% disagreement in the ACTs measured with the Hemochron Response compared to the Hemochron Signature Elite. In conclusion, the Hemochron Response and Hemochron Signature Elite ACT values cannot be used interchangeably. Institutions using these 2 devices should be cognizant of this difference for ensuring patient safety.

Extramedullary plasmacytoma of the true vocal fold.

We report a rare case of extramedullary plasmacytoma (EMP) of the true vocal fold. Our patient, a 62-year-old woman, presented with dysphonia. On workup, fiberoptic laryngoscopy detected a lesion arising from the anterior half of her left true vocal fold. No evidence of other pathology was noted. The patient underwent radical radiotherapy, and the lesion resolved. Follow-up revealed no sign of recurrence. A type of myeloma, EMP is rare, especially in the larynx. To the best of our knowledge, our patient represents the sixth case of glottic EMP to be reported in the literature.

Sudden cardiac death due to large coronary aneurysm successfully treated with a covered stent and ChromaFlo guidance.

We present the case of a gentleman who presented to our hospital with recurrent episodes of sudden cardiac death treated initially with cardioversion. Immediate coronary angiography revealed a 7 mm aneurysm in the proximal left coronary artery. Using intravascular ultrasound and ChromaFlo technology, the aneurysm was successfully treated with a polytetrafluoroethylene-covered stent and the patient had no further episodes of sudden cardiac death.

Organising pneumonia presenting as acute life threatening pulmonary haemorrhage.

Organising pneumonia, previously called bronchiolitis obliterans organising pneumonia is a clinicopathological entity of unknown aetiology, which has been reported with increasing frequency. Various modes of presentation have been described such as cough, fever, weight loss and alveolar opacities on chest radiograph. Haemoptysis as primary presenting symptom has only rarely been reported. The authors report a case in which massive life-threatening haemoptysis was the major presenting symptom. No aetiology was identified for the haemoptysis and the diagnosis was confirmed on postmortem histology. This case highlights the importance of considering organising pneumonia in the differential diagnosis of acute severe haemoptysis.