Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

OBJECTIVE: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence. MATERIAL AND METHODS: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals. Follow-up identified cancer recurrence and death. A baseline model for cancer recurrence at 3 years was developed from pre-specified clinicopathological variables (age, sex, tumour-node stage, tumour size, location, extramural venous invasion, and treatment). Then, CT perfusion (blood flow, blood volume, transit time and permeability), genetic (RAS, RAF, and DNA mismatch repair), and immunohistochemical markers of angiogenesis and hypoxia (CD105, vascular endothelial growth factor, glucose transporter protein, and hypoxia-inducible factor) were added to assess whether prediction improved over tumour-node staging alone as the main outcome measure. RESULTS: Three hundred twenty-six of 448 participants formed the final cohort (226 male; mean 66 ± 10 years. 227 (70%) had ≥ T3 stage cancers; 151 (46%) were node-positive; 81 (25%) developed subsequent recurrence. The sensitivity and specificity of staging alone for recurrence were 0.56 [95% CI: 0.44, 0.67] and 0.58 [0.51, 0.64], respectively. The baseline clinicopathologic model improved specificity (0.74 [0.68, 0.79], with equivalent sensitivity of 0.57 [0.45, 0.68] for high vs medium/low-risk participants. The addition of prespecified CT perfusion, genetic, and immunohistochemical markers did not improve prediction over and above the clinicopathologic model (sensitivity, 0.58-0.68; specificity, 0.75-0.76). CONCLUSION: A multivariable clinicopathological model outperformed staging in identifying patients at high risk of recurrence. Promising CT, genetic, and immunohistochemical markers investigated did not further improve prognostication in rigorous prospective evaluation. CLINICAL RELEVANCE STATEMENT: A prognostic model based on clinicopathological variables including age, sex, tumour-node stage, size, location, and extramural venous invasion better identifies colorectal cancer patients at high risk of recurrence for neoadjuvant/adjuvant therapy than stage alone. KEY POINTS: Identification of colorectal cancer patients at high risk of recurrence is an unmet need for treatment personalisation. This model for recurrence, incorporating many patient variables, had higher specificity than staging alone. Continued optimisation of risk stratification schema will help individualise treatment plans and follow-up schedules.

Colorectal Cancer: Performance and Evaluation for CT Colonography Screening- A Multicenter Cluster-randomized Controlled Trial.

Background Most radiologists reporting CT colonography (CTC) do not undergo compulsory performance accreditation, potentially lowering diagnostic sensitivity. Purpose To determine whether 1-day individualized training in CTC reporting improves diagnostic sensitivity of experienced radiologists for 6-mm or larger lesions, the durability of any improvement, and any associated factors. Materials and Methods This prospective, multicenter cluster-randomized controlled trial was performed in National Health Service hospitals in England and Wales between April 2017 and January 2020. CTC services were cluster randomized into intervention (1-day training plus feedback) or control (no training or feedback) arms. Radiologists in the intervention arm attended a 1-day workshop focusing on CTC reporting pitfalls with individualized feedback. Radiologists in the control group received no training. Sensitivity for 6-mm or larger lesions was tested at baseline and 1, 6, and 12 months thereafter via interpretation of 10 CTC scans at each time point. The primary outcome was the mean difference in per-lesion sensitivity between arms at 1 month, analyzed using multilevel regression after adjustment for baseline sensitivity. Secondary outcomes included per-lesion sensitivity at 6- and 12-month follow-up, sensitivity for flat neoplasia, and effect of prior CTC experience. Results A total of 69 hospitals were randomly assigned to the intervention (31 clusters, 80 radiologists) or control (38 clusters, 59 radiologists) arm. Radiologists were experienced (median, 500-999 CTC scans interpreted) and reported CTC scans routinely (median, 151-200 scans per year). One-month sensitivity improved after intervention (66.4% [659 of 992]) compared with sensitivity in the control group (42.4% [278 of 655]; difference = 20.8%; 95% CI: 14.6, 27.0; P < .001). Improvements were maintained at 6 (66.4% [572 of 861] vs 50.5% [283 of 560]; difference = 13.0%; 95% CI: 7.4, 18.5; P < .001) and 12 (63.7% [310 of 487] vs 44.4% [187 of 421]; difference = 16.7%; 95% CI: 10.3, 23.1; P < .001) months. This beneficial effect applied to flat lesions (difference = 22.7%; 95% CI: 15.5, 29.9; P < .001) and was independent of career experience (≥1500 CTC scans: odds ratio = 1.09; 95% CI: 0.88, 1.36; P = .22). Conclusion For radiologists evaluating CT colonography studies, a 1-day training intervention yielded sustained improvement in detection of clinically relevant colorectal neoplasia, independent of previous career experience. Clinical trial registration no. NCT02892721 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Pickhardt in this issue. An earlier incorrect version appeared online and in print. This article was corrected on February 28, 2022.

Cattle-Related Trauma: A 5-Year Retrospective Review in a Adult Major Trauma Center.

INTRODUCTION: Bovine injuries are a common and significant cause of trauma, often requiring admission and operative treatment. We review all bovine-related injuries over 5 years, both emergency and general practitioner (GP) referrals at an adult major trauma center in England. METHODS: Retrospective evaluation was undertaken using the keywords through radiology referrals and hospital admissions speciality databases. By searching patient notes, demographics were collected as well as the mechanism and the situation of injury; trauma scores were calculated using: injury severity score (ISS) and probability of survival (Ps19). The results were divided into emergency patients and GP referrals. RESULTS: Sixty-seven patients were identified retrospectively over 5 years, 44 emergency patients (including 23 major traumas), and 23 GP referrals. Combined (emergency and GP) mean age 52 years old; 67% male; and mean ISS 11. Most common combined mechanism of injury, kicked (n = 23). In emergency patients, trampling injuries were the most common. Eighty-six percent of the trampled patients were major traumas and associated with increased ISS (mean 13). Indirect injuries mainly involved farm gates (92%). Seventy-three percent of bull-related injuries were major traumas and had increased ISS scores (mean 17). Orthopaedics was the most common admitting speciality followed by cardiothoracic and neurosurgery. In emergency patients, fractures were the most common primary injury (n = 20), upper limb followed by spine. In GP, soft-tissue injuries were the most common primary injury. Seventy percent of the emergency referrals required admission and 50% operations. Fracture fixation was the most common operative procedure. Only, one GP referral required an operation. There were significant delays in GP patients presenting. Two patients had a Ps19 score <90. There were two mortalities. CONCLUSION: Cattle-related injuries are a significant cause of severe morbidity and mortality. They are under-reported. Patterns of injury are similar to high-velocity road traffic collisions and bull-related injuries or trampling in particular, should alert the clinician to more significant trauma. Farm gates are a frequent cause of trauma associated with cattle. GP referrals with ongoing symptoms for more than 2 weeks seeking medical advice should alert the clinician to a more serious diagnosis.

Investigation of polycystic ovarian syndrome: variation in practice and impact on the speed of diagnosis.

OBJECTIVE: Accurate diagnosis of polycystic ovarian syndrome (PCOS) enables clinical interventions/cardiometabolic risk factor management. Diagnosis can take over 2 years and multiple clinician contacts. We examined patterns of PCOS-associated biochemical investigations following initial consultation prior to pelvic ultrasound scan (USS). METHODS: We determined in 206 women (i) the range of different biochemical test panels used in the diagnosis of PCOS in primary/secondary care prior to USS relative to national guidance in the UK and (ii) the relation between testing patterns and time to USS to highlight potential delays introduced by inappropriate testing. RESULTS: In these 206 women, 47 different test combinations were requested at initial venepuncture; only 7 (3%) had the test panel suggested in UK guidance (follicle-stimulating hormone/luteinizing hormone/testosterone/sex hormone-binding globulin/prolactin). The number of tests performed prior to USS varied from one test to all seven tests. There was an inverse relation between the number of biochemistry tests requested at initial venepuncture episode and 'time to scan'. Those who had <3 tests had a significantly longer time from first request to USS (median 70 days) than those with 3-7 tests (median 40 days; P = 0.002). One venepuncture episode prior to USS was associated with shorter 'time to scan' (median 29 days) than those with 2-4 episodes (median 255 days; P < 0.001). CONCLUSION: There was no identifiable pattern to biochemical investigations requested as part of the initial diagnostic evaluation in women with suspected PCOS. We recommend standardization of the initial biochemical panel of analytes for PCOS workup, with incorporation into hospital/general practice ordering software systems.

Metastatic small cell lung cancer presenting as acute pancreatitis: Diagnosis with magnetic resonance cholangiopancreatography.

We detail a case of a right hilar small cell lung cancer with pancreatic metastases presenting as acute pancreatitis and being diagnosed on Magnetic Resonance Cholangiopancreatography (MRCP). A 59-year-old male patient had an MRCP performed following an initial computed tomography scan of the abdomen as part of the investigations following admission with acute pancreatitis. The diagnosis was not clear on CT but MRCP was able to confirm the likely diagnosis of pancreatic metastases with primary lung cancer as the underlying cause. The case illustrates the clinical radiological conundrum concurrent acute pancreatitis can produce to the diagnosis of pancreatic metastases along with how the superior tissue characterization of MRI despite the absence of intravenous contrast can be utilized to better identify solid pancreatic lesions and contribute towards the diagnosis. The superior field of view T2 coronal and localizer images on MRCP, compared to other standard abdominal imaging modalities, in this scenario enabled the right hilar lung primary to be diagnosed.

Influence of tumor histology on preoperative staging accuracy of breast metastases to the axilla.

Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008-31st May 2009 with breast lesions categorized R4-R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound-guided NCB was performed on nodes radiologically classified R3-R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S-guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p < 0.0019).