Can radiomic feature analysis differentiate adrenal metastases from lipid-poor adenomas on single-phase contrast-enhanced CT abdomen?

AIM: To assess if radiomic feature analysis could help to differentiate between the lipid-poor adenomas and metastases to the adrenal glands. MATERIALS AND METHODS: Eighty-six patients (women:men 42:44; mean age 66 years) with biopsy-proven adrenal metastases and 55 patients (women:men 39:16; mean age 67 years) with lipid-poor adenomas who underwent contrast-enhanced, portal-venous phase CT of the abdomen. Radiomic features were extracted using the PyRadiomics extension for 3D Slicer. Following elastic net regularisation, seven of 1,132 extracted radiomic features were selected to build a radiomic signature. This was combined with patient demographics to create a predictive nomogram. The calibration curves in both the training and validation cohorts were assessed using a Hosmer-Lemeshow test. RESULTS: The radiomic signature alone yielded an area under the curve of 91.7% in the training cohort (n=93) and 87.1% in the validation cohort (n=48). The predictive nomogram, which combined age, a previous history of malignancy, and the radiomic signature, had an AUC of 97.2% in the training cohort and 90.4% in the validation cohort. CONCLUSION: The present nomogram has the potential to differentiate between a lipid-poor adrenal adenoma and adrenal metastasis on portal-venous CT.

Impact of COVID-19 on CT-diagnosed acute appendicitis and diverticulitis: was there collateral damage?

AIM: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown. MATERIALS AND METHODS: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free. RESULTS: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443). CONCLUSION: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged.

Advances in radiological staging of colorectal cancer.

The role of imaging in clinically staging colorectal cancer has grown substantially in the 21st century with more widespread availability of multi-row detector computed tomography (CT), high-resolution magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI), and integrated positron-emission tomography (PET)/CT. In contrast to staging many other cancers, increasing colorectal cancer stage does not highly correlate with survival. As has been the case previously, clinical practice incorporates advances in staging and it is used to guide therapy before adoption into international staging guidelines. Emerging imaging techniques show promise to become part of future staging standards.

Prostatitis: imaging appearances and diagnostic considerations.

Acute and chronic inflammation of the prostate gland can be attributed to several underlying aetiologies, including but not limited to, bacterial prostatitis, granulomatous prostatitis, and Immunoglobulin G4-related prostatitis. In this review, we provide an overview of the general imaging appearances of the different types of prostatitis, their distinguishing features and characteristic appearances at cross-sectional imaging. Common imaging pitfalls are presented and illustrated with examples.

Image-guided biopsy in the age of personalised medicine: strategies for success and safety.

Oncology has progressed into an era of personalised medicine, whereby the therapeutic regimen is tailored to the molecular profile of the patient's cancer. Determining personalised therapeutic options is achieved by using tumour genomics and proteomics to identify the specific molecular targets against which candidate drugs can interact. Several dozen targeted drugs, many for multiple cancer types are already widely in clinical use. Molecular profiling of tumours is contingent on high-quality biopsy specimens and the most common method of tissue sampling is image-guided biopsy. Thus, for radiologists performing these biopsies, the paradigm has now shifted away from obtaining specimens simply for histopathological diagnosis to acquiring larger amounts of viable tumour cells for DNA, RNA, or protein analysis. These developments have highlighted the central role now played by radiologists in the delivery of personalised cancer care. This review describes the principles of molecular profiling assays and biopsy techniques for optimising yield, and describes a scoring system to assist in patient selection for percutaneous biopsy.

Tumour markers and their utility in imaging of abdominal and pelvic malignancies.

The utility of tumour biomarkers has increased considerably in the era of personalised medicine and individualised therapy in oncology. Biomarkers may be prognostic or predictive, and only a handful of markers are currently US Food and Drug Administration (FDA)-approved for clinical use. Tumour markers have a wide array of uses such as screening, establishing a differential diagnosis, assessing risk, prognosis, and treatment response, as well as monitoring disease status. Major overlap exists between biomarkers and their associated pathologies; therefore, despite suggestive imaging features, establishing a differential diagnosis may be challenging for the radiologist. We review common biomarkers that are of interest to radiologists such as carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), prostate-specific antigen (PSA), beta human chorionic gonadotropin (ß-hCG), carbohydrate antigen 19-9 (CA 19-9), alpha fetoprotein (AFP), and carbohydrate or cancer antigen 125 (CA 125), as well as their associated malignant and non-malignant pathologies. We also present relevant case examples from our practice.

Review of external referrals to a regional stroke centre: it is not just about thrombectomy.

AIMS: To determine the experience of a regional stroke referral centre of external referrals for endovascular thrombectomy (EVT) in patients with symptoms of acute ischaemic stroke (AIS) and large vessel occlusion (LVO). MATERIALS AND METHODS: Data were collected prospectively over two 4-month periods (2017-2018) on consecutive external referrals for EVT. Baseline demographics, imaging findings, and key time parameters were recorded. Reasons for not transferring patients and for not performing EVT were recorded. Key time intervals were calculated and compared between the transferred and non-transferred group with and without intracranial occlusion and between the transferred patients who underwent thrombectomy and those who did not. RESULTS: Two hundred and sixty-two patients were referred. Sixty-one percent (n=159) were accepted and transferred for treatment. Of those transferred, 86% (n=136) had EVT. Fourteen percent (n=23) were unsuitable for EVT on arrival due to no vessel occlusion (48% n=11), poor Alberta Stroke Program Early CT Score (ASPECTS)/established infarct (30%, n=7) haemorrhage (9%, n=2), and clinical recovery (13% n=3). One hundred and three patients (39%) were ineligible for EVT following phone discussion due to absence of intracranial occlusion (59%, n=61), low ASPECTS (22%, n=23), distal occlusion (4%, n=4), low/improving National Institutes of Health Stroke Scale (NIHSS; 10.7%, n=11), and poor modified Rankin Scale (mRS) at baseline (3%, n=3). Patients with LVO but not transferred had longer onset to hospital arrival time compared with those transferred 151.5 versus 91 minutes (p<0.005), with a trend also toward a longer door to CT/CTA 40 minutes versus 30 minutes (p=0.142). CONCLUSION: These data provide valuable insights into the service provision of a comprehensive stroke network. The present rates of EVT and futile transfers are modest compared to published data. Access to neuroradiology and specialised stroke assessment is crucial to optimise time to treatment.

Neuroimaging of central diabetes insipidus-when, how and findings.

Central or neurogenic diabetes insipidus (CDI) is due to deficient synthesis or secretion of antidiuretic hormone (ADH), also known as arginine vasopressin peptide (AVP). It is clinically characterised by polydipsia and polyuria (urine output > 30 mL/kg/day) of dilute urine (< 250 mOsm/L). It is the result of a defect in one of more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei of the hypothalamus, median eminence of the hypothalamus, infundibulum or the posterior pituitary gland. A focused MRI pituitary gland or sella protocol is essential. There are several neuroimaging correlates and causes of CDI, illustrated in this review. The most common causes are benign or malignant neoplasms of the hypothalamic-pituitary axis (25%), surgery (20%), head trauma (16%) or familial causes (10%). No cause is identified in up to 30% of cases. Knowledge of the anatomy and physiology of the hypothalamo-neurohypophyseal axis is crucial when evaluating a patient with CDI. Establishing the aetiology of CDI with MRI in combination with clinical and biochemical assessment facilitates appropriate targeted treatment. The aim of the pictorial review is to illustrate the wide variety of causes of CDI on neuroimaging, highlight the optimal MRI protocol and to revise the detailed neuroanatomy and neurophysiology required to interpret these studies.

Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.

In HIV-1-infected individuals on currently recommended antiretroviral therapy (ART), viremia is reduced to <50 copies of HIV-1 RNA per milliliter, but low-level residual viremia appears to persist over the lifetimes of most infected individuals. There is controversy over whether the residual viremia results from ongoing cycles of viral replication. To address this question, we conducted 2 prospective studies to assess the effect of ART intensification with an additional potent drug on residual viremia in 9 HIV-1-infected individuals on successful ART. By using an HIV-1 RNA assay with single-copy sensitivity, we found that levels of viremia were not reduced by ART intensification with any of 3 different antiretroviral drugs (efavirenz, lopinavir/ritonavir, or atazanavir/ritonavir). The lack of response was not associated with the presence of drug-resistant virus or suboptimal drug concentrations. Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection.

Is levomepromazine stable over time?

Levomepromazine (methotrimeprazine) is an anti-psychotic used at low dose for the control of nausea and vomiting. When levomepromazine hydrochloride as Nozinan® is diluted with 0.9% sodium chloride at concentrations ranging from 0.13 to 6.25 mg/ml, and stored in polypropylene syringes, the drug is stable for at least 14 days.

The role of percutaneous CT-guided biopsy of an adrenal lesion in patients with known or suspected lung cancer.

PURPOSE: To determine the sensitivity, specificity, and complication rate of percutaneous adrenal biopsy in patients with known or suspected lung cancer. METHODS: This study was approved by the Institutional Review Board at our institution as a retrospective analysis; therefore, the need for informed consent was waived. All percutaneous adrenal biopsies performed between April 1993 and May 2019 were reviewed. 357 of 582 biopsies were performed on 343 patients with known or suspected lung cancer (M:F 164:179; mean age 66 years). The biopsy results were classified into malignant, benign, or non-diagnostic. The final diagnosis was established by pathology (biopsy and/or surgical resection) or imaging follow-up on CT for at least 12 months following the biopsy. Patients with less than 12 months follow-up were excluded (n = 44). Complications were recorded. RESULTS: The final diagnosis was metastatic lung cancer in 235 cases (77.8%), metastasis from an extrapulmonary primary in 2 cases (0.7%), pheochromocytoma in 2 cases (0.7%), and benign lesions in 63 cases (20.9%). Percutaneous adrenal gland biopsy had a sensitivity of 97% and specificity of 100% for lung cancer metastases. The non-diagnostic rate was 0.6%. Larger lesions were more likely to be malignant (p = 0.0000) and to be correctly classified as a lung metastasis (p = 0.025). The incidence of minor complications was 1.1%. There were no major complications. CONCLUSION: Over 20% of adrenal lesions in patients with known or suspected lung cancer were not related to lung cancer. Percutaneous adrenal gland biopsy is a safe procedure, with high sensitivity and specificity for lung cancer metastases.

Pathological features of colorectal carcinomas in MYH-associated polyposis.

AIMS: MYH is a DNA glycosylase in the base excision repair pathway. Germ-line biallelic mutations in the MYH gene are associated with the development of multiple colorectal adenomas and colorectal carcinoma (CRC). A slightly increased risk of CRC is suggested in monoallelic MYH mutation carriers. The aim was to characterize the histopathological features of carcinomas from biallelics and monoallelics. METHODS AND RESULTS: Clinicopathological features of 57 colorectal carcinomas from 50 patients identified in familial CRC registries were recorded. These included 16 cancers from 14 MYH biallelics; 25 cancers from 22 MYH monoallelics; and 16 cancers from 14 controls. Carcinomas in biallelics demonstrated tubular, papillary or cribriform patterns as the predominant histological subtype, and main histological groups differed according to mutation status (P = 0.0053). All biallelic cancers were low grade, with high-grade tumours more common in monoallelics and controls (P = 0.002). Synchronous polyps were observed in 75% of biallelics, 33% of monoallelics and 43% of controls (P = 0.035). Serrated carcinoma was the predominant type in 12% (3/25) of the monoallelics but in none of the biallelics or controls. MYH immunohistochemistry failed to distinguish between groups. CONCLUSIONS: Neither pathological features nor immunohistochemistry could predict the MYH mutation status of CRCs in this study.

Dimensions of depressive symptoms and cingulate volumes in older adults.

Clinical depression and subthreshold depressive symptoms in older adults have been linked to structural changes in the cingulate gyrus. The cingulate comprises functionally distinct subregions that may have distinct associations with different types, or symptom dimensions, of depression. This study examined the relationship between symptom dimensions of depression and gray matter volumes in the anterior cingulate, posterior cingulate and isthmus of the cingulate in a nonclinical sample. The study included 41 community-dwelling older adults between the ages of 55 and 81. Participants received a structural magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale. Subscale scores for depressed mood, somatic symptoms and lack of positive affect were calculated, and Freesurfer was used to extract cingulate gray matter volumes. Regression analyses were conducted to examine the relationship between depressive symptoms and volumes of cingulate subregions while controlling for sex, age and estimated total intracranial volume. Higher scores on the depressed mood subscale were associated with larger volumes in the left posterior cingulate and smaller volumes in the isthmus cingulate. Higher scores on the somatic symptoms subscale were significantly related to smaller volumes in the posterior cingulate. A trend was observed for a positive relationship between higher scores on the lack of positive affect subscale and larger volumes in the anterior cingulate cortex. These results are consistent with previous findings of altered cingulate volumes with increased depressive symptomatology and suggest specific symptom dimensions of depression may differ in their relationship with subregions of the cingulate.

Mapping of an assembled epitope of human follicle-stimulating hormone-beta utilizing monoclonal antibodies, synthetic peptides, and hormone-receptor inhibition.

Monoclonal antibodies (mabs) to human (h) FSH were utilized to probe epitopes of the beta-subunit of hFSH (hFSH beta). These mabs had an average approximate affinity constant (Ka) of 10(8) M-1 for hFSH beta and 10(7) M-1 for heterodimeric hFSH. Hormone specificity of mabs for hFSH beta was demonstrated by a lack of cross-reactivity with hCG alpha, FSH alpha, or LH alpha. Epitope specificity of each mab was initially assessed by determining whether solid phase mab could bind to [125I]hFSH already bound to mabs in liquid phase. In addition, it was determined whether [125I]mab could bind to hFSH already bound to solid-phase mabs. Both epitope cross-matching protocols indicated that all mabs bound to the same epitopes on hFSH beta. Next, synthetic peptides corresponding to the sequence of hFSH beta were used in an enzyme-linked immunosorbent assay to map this epitope. All mabs bound to peptides 7-19, 1-20, 33-53 and 66-85 but did not bind or bound weakly to peptides 81-100, 95-103, and 103-110. Titration experiments were performed using different concentrations of peptide (0.3-41 nmol) and one mab 3G3 (500 ng-25 ng) in the enzyme-linked immunosorbent assay. The product of the lowest mass of both peptide and antibody which gave a positive result was used to rank the peptides for their binding with mab 3G3. Peptides were ranked in the following descending order of potency: 33-53, 49-67, 66-85 much greater than 16-36, 1-20, 95-103, 52-65, 81-100, and 103-110. Ability of the mabs to inhibit binding of [125I]hFSH to bovine testis membrane receptor (Rec) was also studied. When [125I]hFSH was preincubated with increments of each mab for 2 h at 25 C before adding Rec with further incubation for 16 h, all mabs inhibited [125I]hFSH binding to Rec. The data suggest that most of the hFSH beta molecule has a conformation enabling all antibody recognizable regions to be in close proximity to each other. The present study provides evidence for an assembled epitope comprising in part, amino acids 33-53, which has been previously shown to be involved in receptor binding. Peptide sequences 49-67 and 66-85 are neighboring sequences in this assembled epitope which contains the determinants for receptor binding.

Hormone replacement therapy in the menopause: a suitable animal model.

Female CBA mice, aged 11 months, were treated cyclically with oral ethynyl oestradiol or oestrone sulphate for 3 months. The ovaries of all animals appeared to be atrophied. Target tissues throughout the genital tract showed a response to both oestrogens. Electron microscopy of both the endometrium and the urothelium demonstrated morphological changes characteristic of increased cellular metabolic activity in the treated mice. Endometrial hyperplasia developed in both treatment groups but more pronounced epithelial changes occurred with oestrone sulphate. This hyperplasia was accompanied by a doubling in the number of uterine cytoplasmic oestrogen receptors. A 50% fall in serum levels of luteinizing hormone in the treated mice revealed that the hypothalamic-pituitary system was still intact. Both oestrogens improved skeletal balance by changes in cortical-endosteal bone remodelling. The results suggest that the CBA strain of mouse is a suitable model for the study of the human climacteric and its response to hormone replacement therapy.

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload.

BACKGROUND: Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12-16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. METHODS: A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 +/- 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. RESULTS: Icodextrin significantly increased peritoneal ultrafiltration (885 +/- 210 ml to 1454 +/- 215 ml, p < 0.05) and reduced mean arterial pressure (106 +/- 4 to 96 +/- 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 +/- 0.7% to 7.9 +/- 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0-17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13-5.62, p < 0.05). CONCLUSIONS: Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Management of bilateral flexural deformity of the metacarpophalangeal joints in three alpaca crias.

Three neonatal alpacas were treated for MCP flexural deformities. Two crias responded well to conservative therapy using splints made from fibreglass cast material. One cria with severe deformity failed to respond to conservative treatment but recovered satisfactorily after transection of the suspensory ligament in both legs. It seems that mild cases of flexural deformity of the MCP joint in alpaca crias respond well to conservative therapy but that surgical correction may be required in more severe cases. Sequential transection of the structures limiting extension of the MCP joint may result in fewer complications than previously reported techniques.