Comparing fluorodeoxyglucose positron emission tomography with computed tomography in staging for nodal and distant metastasis in urothelial/bladder cancer.

Objectives: We aim to assess the clinical value of 18F-fluorodeoxyglucose positron (18F-FDG-PET) scan in detecting nodal and distant metastasis compared with computed tomography (CT) scan in patients with urothelial carcinoma or bladder cancer, aiming to improve staging accuracy and thereby better prognosticate and determine therapy. Methods: A retrospective review of 75 patients with invasive bladder cancer (≥T1) who were staged with both CT and 18F-FDG-PET within an 8-week interval was performed for the period between 2015 and 2020. Seventy-two per cent (54/75) had formal pelvic lymph node (LN) dissection or biopsy of lesions suspicious for metastases. FDG-PET definitions for positive sites were assessed depending on SUV Max (nodes with SUVmax >4 at any size, SUV > 2 for lymph nodes >8 mm, or any SUV if the lymph node was >10 mm on axial images). For CT scanning, enlarged LN by RECIST 1.1 criteria (>10 mm) as well as qualitative findings suggesting metastasis were considered positive. The analysis was based on the comparison of CT and 18F-FDG-PET findings to histopathology results from LN dissection or biopsies. Results: Sensitivity, specificity, positive predictive values (PPV) and negative predictive value (NPV) of CT versus FDG-PET for detecting metastasis, in patients who underwent pelvic LN dissection or biopsy of lesions suspicious of metastases, were 46.6% (95% CI: 21%-70%) versus 60% (95% CI: 32%-84%), 100% (95% CI: 91%-100%) versus 83.78% (95% CI: 69%-94%), 100% (95% CI: 63%-100%) versus 60% (95% CI: 32%-84%), and 82.2% (95% CI: 68%-92%) versus 83.78% (95% CI: 69%-94%), respectively. 7/75 (9.3%) patients avoided cystectomy due to 18F-FDG-PET features of metastases that were not detected by CT. Conclusion: FDG-PET may be more sensitive than CT for metastases in the staging of bladder cancer, which resulted in significant avoidance of aggressive local management in cases with occult metastasis.

89Zirconium-labelled girentuximab (89Zr-TLX250) PET in Urothelial Cancer Patients (ZiPUP): protocol for a phase I trial of a novel staging modality for urothelial carcinoma.

INTRODUCTION: Bladder cancer is a lethal disease with a rising incidence on a background of limited conventional imaging modalities for staging (either CT of the chest-abdomen-pelvis or 18F-fluorodeoxyglucose positron emitting tomography (FDG-PET/CT)). CT is known to have relatively low sensitivity for detecting low volume metastatic disease, an important goal when considering surgical interventions entailing significant potential morbidity. FDG is also limited, being predominantly renally excreted and, therefore, producing intense non-specific activity in the urinary tract, which limits its utility to detect bladder and upper tract lesions, or nodal metastases in close proximity to the urinary tract. 89Zirconium-labelled girentuximab (89Zr-TLX250) may have utility in the accurate staging of bladder and urothelial carcinomas, with less renal excretion as compared with FDG; however, this has not previously been investigated. METHODS AND ANALYSIS: 89Zirconium-labelled girentuximab PET in Urothelial Cancer Patients is a single-arm phase I trial examining the feasibility of using 89Zr-TLX250-PET/CT as a staging modality for urothelial and bladder carcinomas by examining isotope uptake by the cancer. This trial will also examine the safety and utility of 89Zr-TLX250-PET/CT in patients either undergoing preoperative staging of bladder or other urothelial carcinomas for curative intent, or with known metastatic urothelial carcinomas. All participants will undergo 89Zr-TLX250-PET/CT and will need to have undergone recent FDG-PET/CT for comparison. This trial aims to recruit 10 participants undergoing preoperative staging and 10 participants with known metastatic disease. The primary endpoint is feasibility defined by the ability to recruit to the target sample size within the study duration; secondary endpoints are safety, tolerability, sensitivity and specificity in detecting lymph node metastases compared with FDG-PET/CT. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the South Metropolitan Health Service Human Research Ethics Committee (RGS0000003940). Eligible patients will only be enrolled after providing written informed consent. Patients will be given a full explanation, in lay terms, of the aims of the study and potential risks including as a written patient information sheet. TRIAL REGISTRATION NUMBERS: ACTRN12621000411842, NCT05046665.

Pituitary function following peptide receptor radionuclide therapy for neuroendocrine tumours.

Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty-six patients with unresectable NETs were included-34 had received PRRT and 32 comparison patients. Median follow-up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life.

A Case Report of Syndromic Multinodular Goitre in Adolescence: Exploring the Phenotype Overlap between Cowden and DICER1 Syndromes.

BACKGROUND: Hereditary tumour predisposition syndromes may increase the risk for development of thyroid nodules at a young age. We present the case of an adolescent female with Cowden syndrome who had some atypical phenotypic features which overlapped with the DICER1 syndrome. MATERIAL AND METHODS: A 17-year-old female presented with a 3-month history of progressive right neck swelling. Fine needle cytology of the thyroid revealed a follicular neoplasm with features suggestive of follicular variant of papillary thyroid carcinoma and she underwent a hemithyroidectomy. Enlarging nodules in the remaining thyroid led to a completion thyroidectomy at 19 years of age. The patient's past medical history included an ovarian mixed malignant germ cell tumour, pulmonary nodules and cysts, renal cysts, mucocutaneous lesions, an arachnoid cyst, and a fibrous breast lesion. Macrocephaly was noted on physical examination. RESULTS: Based on the patient's complex phenotype and young age, a hereditary predisposition syndrome was suspected and genetic testing of PTEN and DICER1 was undertaken. A heterozygous truncating germ-line PTEN mutation was identified, which combined with clinical findings, met criteria for the diagnosis of Cowden syndrome. Additional loss of heterozygosity of the wild-type PTEN allele was detected in the right thyroid lesion and ovarian tumour. No DICER1 mutations were identified. CONCLUSIONS: Genetic testing was crucial in elucidating this patient's predisposition to the early development of neoplastic and non-neoplastic conditions. Our report also highlights the phenotypic overlap between the Cowden and DICER1 syndromes and illustrates the importance of recognising the variable phenotypic features of hereditary syndromes in order to enable timely implementation of appropriate care.

Anemia complicating type 2 diabetes: Prevalence, risk factors and prognosis.

AIMS: To determine the prevalence, risk factors and prognosis of anemia in representative community-based patients with type 2 diabetes. METHODS: Data from the Fremantle Diabetes Study Phase II (FDS2; n=1551, mean age 65.7years, 51.9% males) and Busselton Diabetes Study (BDS; n=186, mean age 70.2years, 50.0% males) cohorts, and from 186 matched BDS participants without diabetes, were analyzed. The prevalence of anemia (hemoglobin ≤130g/L males, ≤120g/L females) was determined in each sample. In FDS2, associates of anemia were assessed using multiple logistic regression and Cox proportional hazards modeling identified predictors of death during 4.3±1.2years post-recruitment. RESULTS: The prevalence of anemia at baseline was 11.5% in FDS2 participants, 17.8% in BDS type 2 patients and 5.4% in BDS participants without diabetes. In FDS2, 163 of 178 patients with anemia (91.6%) had at least one other risk factor (serum vitamin B12<140pmol/L, serum ferritin <30µg/L and/or transferrin saturation<20%, serum testosterone <10nmol/L (males), glitazone therapy, estimated glomerular filtration rate (eGFR) <60mL/min 1.73m2, malignancy, hemoglobinopathy). More anemic than non-anemic FDS2 patients died (28.7% versus 8.0%; P<0.001). After adjustment for other independent predictors (age as time-scale, male sex, Aboriginality, marital status, smoking, eGFR), anemia was associated with a 57% increase in mortality (P=0.015). CONCLUSIONS: Type 2 diabetes at least doubles the risk of anemia but other mostly modifiable risk factors are usually present. Anemia is associated with an increased risk of death after adjustment for other predictors.

Higher serum undercarboxylated osteocalcin and other bone turnover markers are associated with reduced diabetes risk and lower estradiol concentrations in older men.

CONTEXT: In mice, undercarboxylated osteocalcin (ucOC) modulates insulin secretion and sensitivity and increases testosterone (T) secretion from Leydig cells, but human data are lacking. We hypothesized that ucOC is associated with diabetes risk and modulates sex hormone concentrations in older men, distinct from other bone turnover markers. PARTICIPANTS: PARTICIPANTS were community-dwelling men aged 70 to 89 years resident in Perth, Western Australia. MAIN OUTCOME MEASURES: Serum total osteocalcin (TOC), N-terminal propeptide of type I collagen (P1NP), and collagen type I C-terminal cross-linked telopeptide (CTX) were measured by immunoassay, and ucOC by hydroxyapatite binding. Plasma total T, DHT, and estradiol (E2) were assayed by mass spectrometry. RESULTS: Excluding men with osteoporosis or conditions affecting sex hormones or on bisphosphonates, glucocorticoids, or warfarin, 2966 men were included. In multivariate analyses, higher ucOC was associated with reduced diabetes risk (odds ratio [OR] per 1 SD increase = 0.55, P < .001). Similar results were seen for TOC (OR = 0.60, P < .001), P1NP (OR = 0.64, P < .001), and CTX (OR = 0.60, P < .001) but not ucOC/TOC. When all 4 markers were included in the fully adjusted model, higher ucOC (OR = 0.56, P < .001) and CTX (OR = 0.76, P = .008) remained associated with reduced diabetes risk. E2 was inversely associated with ucOC (coefficient -0.04, P = .031), TOC (-0.05, P = .001) and CTX (-0.04, P = .016); and positively with ucOC/TOC (0.05, P = .002). DHT was inversely associated with ucOC/TOC (-0.04, P = .040). T was not associated with bone turnover. CONCLUSIONS: Higher bone remodeling rates are associated with reduced diabetes risk in older men. Higher ucOC is both a marker of bone remodeling and an independent predictor of reduced diabetes risk. E2 is inversely associated with bone turnover markers. We found no evidence ucOC modulates circulating T in older men.