Non-prostate cancer tumours: incidence on 18F-DCFPyL PSMA PET/CT and uptake characteristics in 1445 patients.

PURPOSE: With increasing use of PSMA PET/CT in the staging and restaging of prostate cancer (PCa), the identification of non-prostate cancer tumours (NPCaT) has become an increasing clinical dilemma. Atypical presentations of PSMA expression in prostate cancer and expression in NPCaT are not well established. Understanding the normal and abnormal distribution of PSMA expression is essential in preparing clinically relevant reports and in guiding multidisciplinary discussion and decisions. METHODS: Retrospective review of 1445 consecutive 18F-DCFPyL PSMA PET/CT studies by experienced radiologists and nuclear medicine physicians. Lesions indeterminate for PCa were identified. Correlation was made with patient records, biopsy results, and dedicated imaging. Lesions were then categorized into four groups: 1. Confirmed prostate cancer, metastases, 2. NPCaT 3. Benign, and 4. Indeterminate lesions. RESULTS: 68/1445 patients had lesions atypical for prostate cancer metastases. These comprised 8/68 (11.8%) atypical prostate cancer metastases, 17/68 (25.0%) NPCaT, 29/68 (42.6%) indeterminate, and 14/68 (20.6%) benign. In the context of the entire cohort, these are adjusted to 8/1445 (0.6%), 17/1445 (1.2%), 29/1445 (2.0%), and 14/1445 (1.0%) respectively. With the exception of Renal Cell Carcinoma (RCC), NPCaT demonstrated no or low PSMA expression. A similar trend was also observed for indeterminate and benign lesions. Conversely, most atypical PCa metastases demonstrated intermediate or high PSMA expression. CONCLUSION: 18F-DCFPyL PSMA PET/CT detection of NPCaT is low. Lesions demonstrating intermediate to high PSMA expression were exclusively prostate cancer metastases, aside from RCC, and lesions detected in organs with high background expression.

Pathological predictors of 18 F-DCFPyL prostate-specific membrane antigen-positive recurrence after radical prostatectomy.

OBJECTIVES: To assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent 18 F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF). PATIENTS AND METHODS: Retrospective analysis of combined 18 F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on 18 F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour. RESULTS: Of the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity. CONCLUSION: 18 F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with 68 Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.

[18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5 ng/mL.

PURPOSE: The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5 ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. METHODS: Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. RESULTS: Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2 ng/mL, 82.1% (23/28) for PSA levels 1-1.99 ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99 ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49 ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2 ng/mL. In those with PSA < 0.5 ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bed recurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. CONCLUSION: [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5 ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

Magnetic resonance enterography for predicting the clinical course of Crohn's disease strictures.

BACKGROUND AND AIMS: Strictures are the most common Crohn's disease complication, but their natural history is unknown. This study aimed to characterize inflammation, predict prognosis, and understand the impact of drug therapy using magnetic resonance enterography (MRE). METHODS: Patients with a stricture diagnosed on MRE over a 5-year period were reviewed for MRE disease extent and inflammation, clinical course, C-reactive protein, response to anti-TNF therapy, endoscopic dilatation, hospitalization, and surgery. RESULTS: 136 patients had 235 strictures (77, one and 59, ≥ 2 strictures). TREATMENT: 46% of patients underwent surgery after a median 6 months; median follow-up for those not requiring surgery was 41 months. Predictors of surgery: Hospitalization because of obstruction predicted subsequent surgery (OR 2.50; 95% CI 1.06-5.90) while anti-TNF therapy commenced at stricture diagnosis was associated with a reduced risk (OR 0.23; 95% CI 0.05-0.99). MRE characteristics associated with surgery were proximal bowel dilatation ≥ 30-mm diameter (OR 2.98; 95% CI 1.36-6.55), stricture bowel wall thickness ≥ 10-mm (OR 2.42; 95% CI 1.11-5.27), and stricture length > 5-cm (OR 2.56; 95% CI 1.21-5.43). 81% of patients with these three adverse MRE features required surgery versus 17% if none were present (P < 0.001). Accuracy for these three MRE variables predicting surgery was high (AUC 0.76). CONCLUSION: Magnetic resonance enterography findings in Crohn's disease strictures are highly predictive of the disease course and the need for future surgery. MRE may also identify who would benefit from treatment intensification. Anti-TNF therapy is associated with reduced risk of surgery and appears to alter the natural history of this complication.

Body Composition Differences Between Excess Weight Loss ≥ 50% and < 50% at 12 Months Following Bariatric Surgery.

BACKGROUND: The relationship between weight loss and body composition is undefined after bariatric surgery. The objective of this study was to compare body composition changes in patients with excess weight loss ≥ 50% (EWL ≥ 50) and < 50% at 12 months post-operatively (EWL < 50). METHODS: A prospective cohort study was completed on patients undergoing bariatric surgery at two tertiary hospitals between 2017 and 2021. Body composition was measured with dual-energy X-ray absorptiometry immediately before surgery, and at 1, 6, and 12 months post-operatively. Body mass index (BMI), fat mass (FM), lean body mass (LBM), and skeletal muscle index (SMI) trajectories were analysed between patients with EWL ≥ 50% and EWL < 50%. RESULTS: Thirty-seven patients were included in this series (EWL ≥ 50% n = 25, EWL < 50% n = 12), comprising of both primary and revisional bariatric surgery cases, undergoing a sleeve gastrectomy (62.2%), Roux-en-Y gastric bypass (32.4%), or one anastomosis gastric bypass (5.4%). The EWL ≥ 50% group demonstrated a more optimal mean FM-to-LBM loss ratio than the EWL < 50% group. EWL ≥ 50% patients lost 2.0 kg more FM than EWL < 50% patients for each 1 kg of LBM lost. EWL ≥ 50% was also associated with an increase in mean SMI% over 12 months (5.5 vs. 2.4%; p < 0.0009). Across the whole cohort, the first month after surgery accounted for 67.4% of the total LBM reduction that occurred during the 12-month post-operative period. CONCLUSION: This data suggests EWL ≥ 50% is associated with a more optimal body composition outcome than EWL < 50%. LBM reduction occurs predominantly in the early post-operative period.

Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial.

BACKGROUND: Strictures are the most common structural complication of Crohn's disease. Surgery and endoscopic balloon dilation are the main treatments; drug therapy has been considered contraindicated. Given that most strictures have an inflammatory component, we aimed to find out whether strictures are responsive to drug treatment and whether intensive drug therapy is more effective than standard drug therapy. METHODS: This open-label, single-centre, randomised controlled trial was performed in one specialist inflammatory bowel disease centre in Australia. Patients aged 18 years or older with Crohn's disease were included. Eligible patients had a de novo or postoperative anastomotic intestinal stricture on MRI or ileocolonoscopy, symptoms consistent with chronic or subacute intestinal obstruction (postprandial abdominal pain in the presence of a confirmed stricture), and evidence of active intestinal inflammation. Patients were randomly assigned (2:1) to receive intensive high-dose adalimumab (160 mg adalimumab once per week for 4 weeks followed by 40 mg every 2 weeks, with escalation of dose at 4 months and 8 months if assessment of disease activity indicated active inflammation) plus thiopurine (initial dose of azathioprine 2·5 mg/kg or mercaptopurine 1·5 mg/kg, with dose adjustment based on thiopurine metabolite testing) or standard adalimumab monotherapy (160 mg at week 0, 80 mg at week 2, then 40 mg every 2 weeks) using stratified fixed block randomisation. Stratification factors were stricture dilation at study baseline colonoscopy and current biologic drug use. The primary endpoint was improvement (decrease) in the 14-day obstructive symptom score at 12 months by one or more points compared with baseline. This trial is registered with ClinicalTrials.gov, NCT03220841, and is completed. FINDINGS: Between Sept 10, 2017, and Sept 6, 2019, 123 patients were screened and 77 randomly assigned to intensive adalimumab plus thiopurine treatment (n=52) or standard adalimumab treatment (n=25). At 12 months, improvement in obstructive symptom score was noted in 41 (79%) of 52 patients in the intensive treatment group and 16 (64%) of 25 in the standard treatment group (odds ratio [OR] 2·10 [95% CI 0·73-6·01]; p=0·17). Treatment failure occurred in five (10%) patients in the intensive treatment group versus seven (28%) in the standard treatment group (OR 0·27 [95% CI 0·08-0·97]; p=0·045); four patients in each group required stricture surgery (0·44 [0·10-1·92]; p=0·27). Crohn's Disease Activity Index was less than 150 in 36 (69%) patients in the intensive treatment group versus 15 (60%) in the standard treatment group (1·50 [0·56-4·05]; p=0·42). MRI at 12 months showed improvement using the stricture MaRIA score (≥25%) in 31 (61%) of 51 versus seven (28%) of 25 patients (3·99 [1·41-11·26]; p=0·0091). MRI complete stricture resolution was seen in ten (20%) versus four (16%) patients (1·28 [0·36 to 4·57]; p=0·70). Intestinal ultrasound at 12 months showed improvement (>25%) in bowel wall thickness in 22 (51%) of 43 versus seven (33%) of 21 patients (2·10 [0·71 to 6·21]; p=0·18). Faecal calprotectin normalised in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Normalisation of CRP was seen in 32 (62%) versus 11 (44%) patients (2·04 [0·77-5·36]; p=0·15). Eight (15%) patients in the intensive treatment group and four (16%) in the standard treatment group reported serious adverse events. No deaths occurred during the study. INTERPRETATION: Crohn's disease strictures are responsive to drug treatment. Most patients had improved symptoms and stricture morphology. Treat-to-target therapy intensification resulted in less treatment failure, a reduction in stricture-associated inflammation, and greater improvement in stricture morphology, although these differences were not significantly different from standard therapy. FUNDING: Australian National Health and Medical Research Council, Gastroenterological Society of Australia Ferring IBD Clinician Establishment Award, Australasian Gastro Intestinal Research Foundation, AbbVie, and the Spotlight Foundation.

The inferior vena cava: anatomical variants and acquired pathologies.

The inferior vena cava (IVC) is the largest vein in the body, draining blood from the abdomen, pelvis and lower extremities. This pictorial review summarises normal anatomy and embryological development of the IVC. In addition, we highlight a wide range of anatomical variants, acquired pathologies and a common pitfall in imaging of the IVC. This information is essential for clinical decision making and to reduce misdiagnosis.

Body Composition Changes Following a Very-Low-Calorie Pre-Operative Diet in Patients Undergoing Bariatric Surgery.

BACKGROUND: Fatty liver in obese patients increases the technical difficulty of bariatric surgery. Pre-operative weight loss with a very-low-calorie diet (VLCD) is commonly used to facilitate surgery. Few studies have quantified the systemic effect of rapid pre-operative weight loss on body composition. The objective of this study is to evaluate body composition changes in bariatric surgery patients undergoing a VLCD. METHODS: Body composition assessments were performed between August 2017 and January 2019 using dual-energy X-ray absorptiometry immediately before and after a 2-week VLCD at St Vincent's Hospital Melbourne. Data collected prospectively pre- and post-VLCD included total body weight, excess body weight, body mass index (BMI), lean body mass (LBM), fat mass (FM) and bone mineral content (BMC). The pre- and post-operative results were compared. RESULTS: Forty-four patients completed both the 2-week VLCD and body composition assessments. Following a 2-week VLCD, patients lost a mean of 4.5 kg (range - 0.3 to 9.5) in a total body weight and 8.8% (range - 0.9 to 17.1) of excess body weight, with a mean reduction in body mass index of 1.6 kg/m2 (range - 0.2 to 3.1). Loss of LBM was 2.8 kg and was significantly greater than loss of FM, 1.7 kg (p < 0.05). BMC changes were insignificant. CONCLUSION: A VLCD is an effective tool for pre-operative weight reduction. In this cohort, a large amount of the total weight loss was attributed to a loss of lean body mass. The impact of significant lean body mass loss and its relationship to short- and long-term health outcomes warrants further assessment.

Abdominal wall metastasis following open nephroureterectomy for upper tract urothelial carcinoma in a patient with Lynch syndrome.

A 74-year-old man developed the rare complication of an abdominal wall metastasis following open nephroureterectomy for upper tract urothelial carcinoma (UTUC). This occurred in the setting of synchronous contralateral ureteric and metachronous colorectal carcinomas. Immunohistochemistry demonstrated loss of the mutS homolog 6 (MSH6) mismatch repair (MMR) protein in the metastatic abdominal wall and colonic lesions, which in conjunction with meeting the Amsterdam II criteria, is strongly suggestive of Lynch syndrome (LS). Surgical resection of the recurrence was performed with clear margins and neither recurrence nor spread during short-term follow-up.