transsphenoidal surgery for secreting pituitary microadenomas: results with intraoperative application of absolute alcohol

ABSTRACT Background: Pituitary adenomas represent a quite frequent neurosurgical disease. Secreting pituitary adenomas are represented by PRL, GH, ACTH and TSH tumours; the rate of postoperative hormonal recurrence is not ineligible. Methods: We present 106 patients affected by secreting pituitary microadenomas operated through transsphenoidal approach from 1998 through to 2008; in 54 (group 1) patients, intraoperative absolute alcohol was applied, while in the other 52 (group 2) it was not employed. The indications and the intraoperative technique of absolute alcohol application are presented. Hormonal recurrence was treated by hypofractionated stereotactic radiotherapy and/or medical therapy. Results: Postoperative hormonal and clinical remission was achieved in 50 and 47 patients respectively of group one and group two. At the first follow-up control, after 3 months from surgery, no patient of both groups presented hormonal/clinical recurrence. Six months after surgery, no patient of group one presented hormonal recurrence, while two patients of group 2 presented hormonal recurrence. After 2 years from surgery, two patients of group 1 and 4 patients of group 2 presented hormonal recurrence. Three years after operation, hormonal hypersecretion recurred in three patients of group one and in six patients of group 2. At 5 years follow-up, six patients of group one and 8 of group two presented hormonal recurrence. Conclusions: Intraoperative application of absolute alcohol, in selected cases, resulted useful to achieve better results in secreting pituitary microadenomas concerning both postoperative hormonal recurrence and hormonal persistence

A twisted tale-radiological imaging features of COVID-19 on ¹⁸F-FDG PET/CT

The COVID-19 pandemic has had a major impact on health care systems across the globe in a short period of time. There is a growing body of evidence surrounding the findings on hybrid imaging with FDG-PET/CT, and this case highlights the importance of molecular imaging in better understanding of the biomarkers of the disease which ultimately determine the success in building a model to predict the disease severity and monitoring the response to treatment

Revalidation of PET/computed tomography criteria (Hopkins criteria) for the assessment of therapeutic response in lung cancer patients: inter-reader reliability, accuracy and survival outcomes

BACKGROUND/AIM: Systematic reporting using qualitative evaluation of PET/computed tomography (CT) results has been demonstrated to be very accurate and reproducible in posttherapy assessment of lung cancer (so-called Hopkins criteria). Our aim was to test, in a different cohort of patients, the Hopkins criteria for assessment of therapeutic response in lung cancer and to compare the results with those obtained using a semi-quantitative evaluation of uptake. METHODS: This is a retrospective study. A total of 85 patients with known lung cancer who underwent fluorine-18 fluorodeoxyglucose PET/CT assessment within 24 weeks (mean 7.9 weeks) of completion of treatment were included. Treatments included surgical resection, chemotherapy, radiation therapy, immunotherapy or combinations thereof. PET/CT interpretation was done by two nuclear medicine physicians, and discrepancies were resolved by a third interpreter. Studies were scored both according to the Hopkins criteria using qualitative assessment of tracer uptake for the primary tumour, locoregional disease in the mediastinum and distant metastatic sites and by applying the same five-point score using a semi-quantitative measure, maximum standardized uptake value. Overall scores of 1, 2 and 3 were considered negative for residual disease, while scores of 4 and 5 were considered positive. Patients were followed up for a median of 18.5 months (range 2-139 months). Kaplan-Meier plots with a Mantel-Cox log-rank test were performed, considering death as the endpoint. Inter-reader variability was assessed using percent agreement and kappa statistics. RESULTS: The Cohen κ coefficient analysis showed substantial agreement between the two interpreters on the five-point Hopkins criteria scoring, with a κ of 0.73. There was almost perfect agreement between the interpreters with respect to classification as positive or negative according to the Hopkins criteria, with a κ of 0.89. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the Hopkins criteria were 88.5% [95% confidence interval (CI) 80.6-96.5%), 79.2% (95% CI 63.2-95.1%), 91.5% (95% CI 84.4-98.6%), 73.1% (95% CI 61.8-84.4%) and 85.9% (95% CI 78.5-93.3%), respectively. There was almost perfect agreement between the qualitative and semi-quantitative scoring with a κ of 0.87, with sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the semi-quantitative Hopkin's criteria of 86.9% (95% CI 78.4-95.4%), 79.2% (95% CI 62.9-95.4%), 91.4% (95% CI 84.2-98.6%), 70.4% (95% CI 58.6-82.1%) and 84.7% (95% CI 80.8-92.4%), respectively. CONCLUSION: The use of Hopkins criteria for posttherapy assessment in patients with lung cancer represents an easy and reproducible method with substantial to almost perfect interobserver agreement and high positive predictive value and accuracy; moreover, it is easily understood by referring physicians. Additionally, there was no significant difference when applying a semi-quantitative measure to the same five-point score

Hormonal regulation of bicarbonate secretion in the biliary epithelium.

Bicarbonate excretion in bile is a major function of the biliary epithelium. It is driven by the apically located Cl-/HCO3- exchanger which is functionally coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylcholine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin

3-T MRI and clinical validation of ultrasound-guided transperineal laser ablation of benign prostatic hyperplasia

Background: Transperineal laser ablation (TPLA) of the prostate is a novel, mini-invasive option for men with lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH). Our aim was to assess the impact of ultrasound-guided TPLA regarding urodynamic improvement and sexual function, monitoring clinical data, postprocedural complications and imaging findings at 3-T multiparametric magnetic resonance imaging. Methods: Forty-four patients aged ≥ 50 affected with moderate to severe LUTS (International Prostate Symptoms score ≥ 12) due to benign prostatic obstruction and refractoriness, intolerance or poor compliance to medical therapies underwent US-guided TPLA between May 2018 and February 2020. Clinical measurements included PSA, uroflowmetry, sexual function assessment (using the International Index of Erectile Function and Male Sexual Health Questionnaire-Ejaculatory Dysfunction short form) and quality of life questionnaire. Adverse events were evaluated using the Clavien-Dindo scale. Volume changes were measured by MRI and automatic segmentation software during 1-year follow-up. Registration: NCT04044573 – May 5th, 2018, https://www.clinicaltrials.gov Results: MRI assessed the changes over time with a 53% mean reduction of adenoma volume and 71% of the ablated area, associated with clinical and functional improvement and resolution of LUTS in all cases. Five of 44 patients (11.3%) had urinary blockage due to clots and required re-catheterisation for 2 weeks. The overall adverse event rate was 7%. Conclusion: US-guided TPLA performed as a safe, manageable and effective treatment for LUTS. It could be considered an alternative effective mini-invasive procedure to standard treatments for BPH in the outpatient setting

Transperineal Laser Ablation (TPLA) Treatment of Focal Low–Intermediate Risk Prostate Cancer

background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low–intermediate-risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low-to-intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a day hospital setting under local anesthesia. patients underwent regular clinical and functional assessments through the international index of erectile function (IIEF-5) and the International prostatism symptom score (IPSS), PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. results: forty patients were initially included, with fifteen lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. biopsies at 36 months revealed no malignant findings in 20 patients. no deterioration in sexual function or urinary symptoms was recorded. conclusions: FLA appears to be safe, feasible, and effective in the index lesion treatment of low–intermediate-risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life

Non-small-cell lung cancer resectability: diagnostic value of PET/MR.

Purpose To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. Methods Fifty consecutive consenting patients who underwent routine 18F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. Results ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen’s kappa 0.646 – 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen’s kappa 0.627 – 0.823). Conclusion In lung cancer patients PET/MR appears to be a robust technique for preoperative staging

Cerebrospinal fluid biomarkers in cerebral amyloid angiopathy

BACKGROUND: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). OBJECTIVE: To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA. METHODS: We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer’s disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service. RESULTS: We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p < 0.01) median concentrations of Aβ_{38}, Aβ_{40}, Aβ_{42}, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p < 0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ_{38}, Aβ_{40}, Aβ_{42}, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n = 5) and negative (n = 5) scans, PET positive individuals had lower (p < 0.05) concentrations of CSF Aβ_{42}, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an “AD-like” profile. CONCLUSION: CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed

Evolution of 18F-FDG-PET/CT findings in patients following COVID-19 pneumonia: An Initial Investigation

Background: The evolution of pulmonary 18F-FDG uptake is unknown in patients with pneumonia due to SARS-CoV-2 (COVID-19 pneumonia) and in those with persistent respiratory symptoms post-COVID-19 termed Post-COVID-19 Lung-Disease (PCLD). The aim of this study was to assess the temporal evolution of pulmonary 18F-FDG uptake and identify a potential role for the use of 18F-FDG-PET/CT imaging in the management of these patients. Methods: Clinical data and CT imaging of all patients that underwent 18F-FDG-PET/CT imaging at UCLH, Lon-don during the UK pandemic were reviewed to find evidence of active or recovered SARS-CoV-2 infection. Results of PCR tests were used where available. Patients were divided in to acute (early and late) COVID-19 pneumonia, PCLD and asymptomatic recovery. 18F-FDG uptake in the lungs was measured as a target-to-background ratio (SUVmax/SUVmin) TBRlung which was compared to temporal-stage and plasma CRP. Results: There were 50 patients in total (median 61y, range 18-87y, 32-male): 23 incidental acute COVID-19 pneumonia cases identified retrospectively (8 Early, 15 Late), 9 asymptomatic recovered patients, and 18 cases performed for PCLD. In acute COVID-19 patients <3 weeks since disease onset TBRlung was strongly correlated with time since disease onset (rs=0.81, p<0.001)

Clinical Impact of Respiratory Motion Correction in Simultaneous PET/MR with a Joint PET/MR Predictive Motion Model

In Positron Emission Tomography (PET) imaging, patient motion due to respiration can lead to artefacts and blurring, in addition to quantification errors. The integration of PET imaging with Magnetic Resonance (MR) imaging in PET/MR scanners provides spatially aligned complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. We validate our PET respiratory motion correction methodology based on a joint PET-MR motion model, on a patient cohort, showing it can improve lesion detectability and quantitation, and reduce image artefacts. METHODS: We apply our motion correction methodology on 42 clinical PET-MR patient datasets, using multiple tracers and multiple organ locations, containing 162 PET-avid lesions. Quantitative changes are calculated using Standardised Uptake Value (SUV) changes in avid lesions. Lesion detectability changes are explored with a study where two radiologists identify lesions or 'hot spots', providing confidence levels, in uncorrected and motion-corrected images. RESULTS: Mean increases of 12.4% for SUV_peak and 17.6% for SUV_max following motion correction were found. In the detectability study, an increase in confidence scores for detecting avid lesions is shown, with a mean score of 2.67 rising to 3.01 (out of 4) after motion correction, and a detection rate of 74% rising to 84%. Of 162 confirmed lesions, 49 lesions showed an increase in all three metrics SUV_peak, SUV_max and combined reader confidence scores, whilst only two lesions showed a decrease. We also present a number of clinical case studies, demonstrating the effect respiratory motion correction of PET data can have on patient management, with increased numbers of lesions detected, improved lesion sharpness and localisation, as well as reduced attenuation-based artefacts. CONCLUSION: We demonstrate significant improvements in quantification and detection of PET-avid lesions, with specific case study examples showing where motion correction has the potential to have an effect on patient diagnosis or care