Striatal Dopamine Deficit and Motor Impairment in Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND: Idiopathic normal pressure hydrocephalus can present with parkinsonism. However, abnormalities of the striatal dopamine reuptake transporter are unclear. OBJECTIVES: To explore presence and features of striatal dopaminergic deficit in subjects with idiopathic normal pressure hydrocephalus as compared to Parkinson's disease (PD) patients and healthy controls. METHODS: We investigated 50 subjects with idiopathic normal pressure hydrocephalus, 25 with PD, and 40 healthy controls. All participants underwent [123 I]-N-ω-fluoropropyl-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane and single-photon emission computed tomography to quantify the striatal dopamine reuptake transporter binding. All subjects with idiopathic normal pressure hydrocephalus underwent a levodopa (l-dopa) challenge test and magnetic resonance imaging to evaluate ventriculomegaly and white matter changes. Gait, cognition, balance, and continence were assessed with the Idiopathic Normal Pressure Hydrocephalus Rating Scale, and parkinsonism with the motor section of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale. All patients completed a 2-year follow-up. RESULTS: A total of 62% of patients with idiopathic normal pressure hydrocephalus featured a reduced striatal dopamine reuptake transporter binding, which correlated with the severity of parkinsonism but not with features of ventriculomegaly or white matter changes. Unlike PD, this dopaminergic deficit in idiopathic normal pressure hydrocephalus was more symmetric and prominent in the caudate nucleus. CONCLUSIONS: Subjects with idiopathic normal pressure hydrocephalus can present a reduction of striatal dopamine reuptake transporter binding, which is consistent with the severity of parkinsonism and qualitatively differs from that found in PD patients. Longitudinal interventional studies are needed to prove a role for striatal dopamine reuptake transporter deficit in the pathophysiology of idiopathic normal pressure hydrocephalus. © 2020 International Parkinson and Movement Disorder Society.

Radio-guided vs clip-guided localization of nonpalpable mass-like lesions of the breast from a screened population: A propensity score-matched study.

BACKGROUND AND OBJECTIVES: An accurate localization is mandatory to tailor breast lumpectomy in nonpalpable cancers. The aim of this study was to compare radio-guided localization (ROLL) vs ultrasound localization of a titanium clip with collagen (TCC) in nonpalpable mass-like breast cancers. METHODS: Two hundred seventy-three consecutive patients were reviewed: 64 patients were localized by TCC and 209 patients by ROLL. Propensity score-matched analysis was performed. Margin status and reintervention rates were compared. Adequacy of resection was expressed as the calculated resection ratio (CRR) considering lesion size. Loco-regional and distant recurrence rates were assessed with ROLL vs TCC. RESULTS: No differences were found with ROLL vs TCC in clear margins (90.6% vs 89.1%; odds ratio, 0.74; P = 0.64) or reoperations (6.7% vs 1.6%; P = 0.529). ROLL allowed more tailored resections compared with TCC (adjusted CRR, 1.7 vs 2.7; P = 0.0008), particularly in lesions with associated extensive intraductal component (CRR, 3.0 vs 4.5; P = 0.017). Loco-regional recurrence occurred in 1.9% of ROLL patients vs 3.2% of TCC cases (P = 0.628). CONCLUSIONS: ROLL and TCC are equally effective to excise nonpalpable mass-like breast cancers with clear margins, providing similar loco-regional control. However, ROLL allows more tailored breast resections, particularly in lesions with the associated extensive intraductal component.

Radio-guided and clip-guided preoperative localization for malignant microcalcifications offer similar performances in breast-conserving surgery.

Obtaining a tailored breast resection is challenging in microcalcifications detected on screening mammography, and an accurate localization is required. The aim of this study was to compare the efficacy of radio-guided localization (ROLL) versus ultrasound localization of a titanium clip with collagen (TCC) in terms of clear margins, re-intervention rates, excess of resected breast tissue, and operative times in pure malignant microcalcifications detected on screening mammography. Two hundred and twenty-one consecutive patients with malignant microcalcifications detected on screening mammography from a tertiary breast unit were reviewed: 177 patients were localized by TCC and 44 patients by stereotactic ROLL. A propensity score-matched analysis was performed, followed by a logistic regression model, to avoid selection bias. Adequacy of resection was expressed as the calculated resection ratio considering lesion size. No differences were found in clear margins with ROLL versus TCC (77.3% vs 81.8%, adjusted OR 2, P = 0.27). Re-operation rates were similar, being 11.3% with ROLL and 7.4% with TCC (P = 0.627). Mean resection volume was 46.2 cm3 with ROLL versus 54.2 cm3 with TCC (P = 0.222). Adjusted mean calculated resection ratio was 1.8 with ROLL and 2.1 with TCC (P = 0.38). Surgery time was longer with TCC compared to ROLL (69.6 vs 52.7 minutes, P < 0.0001). ROLL and TCC are equally effective to excise malignant microcalcifications with clear margins, providing similar re-intervention rates and resection volumes.

Pseudo-Orthostatic Tremor in Graves' Disease: A Possible Early Sign of Parkinsonism?

Background: Pseudo-orthostatic tremor is a hyperkinetic movement disorder usually associated with other neurological comorbidities, mainly Parkinson's disease. Case report: A 65-year-old male presented with unsteadiness and leg tremor while standing. Electrophysiological evaluation confirmed the presence of pseudo-orthostatic tremor. Blood test showed an undiagnosed Graves' disease. A complete remission of tremor was achieved with methimazole. Dopamine transporter scintigraphy showed a mild reduction of the striatal binding, bilaterally. Discussion: Graves' disease can be associated with pseudo-orthostatic tremor. Thyroid function should be assessed in patients complaining of unsteadiness. The causative role of hyperthyroidism in determining dopaminergic degeneration and uncovering subclinical parkinsonism warrants further investigations.

Comparison between SeHCAT test and clinical response to cholestyramine in patients with chronic diarrhea and high suspicion of bile acid malabsorption: A single-center prospective study.

OBJECTIVES: We aimed to evaluate the clinical response to cholestyramine in patients with functional chronic diarrhea and a high clinical suspicion of bile-acid diarrhea (BAD) investigated with 75-selenium homocholic acid taurine (SeHCAT) test. METHODS: Adult patients attending our outpatient clinic between January and December 2021 for chronic diarrhea with suspicion of BAD were proposed SeHCAT testing and a therapeutic trial of cholestyramine 4-8 g daily. Clinical response to cholestyramine was evaluated at 1, 3, 6, and 12 months. Clinical and demographic data were analyzed according to SeHCAT test results. RESULTS: Among the 50 patients with chronic diarrhea and clinical suspicion of BAD, 13 (26.0%) refused either SeHCAT testing or cholestyramine therapy. Finally, 37 patients (31 females, age 44 ± 14 years) agreed to undergo SeHCAT and were started on cholestyramine (median follow-up 14 months [interquartile range 6-16 months]). Initial response to cholestyramine was similar in patients with positive and negative SeHCAT test results, but improved over time in those with a positive test result. Long-term response (100% vs 65.2%, P = 0.02) and necessity of maintenance therapy for symptom control were more common in those with positive SeHCAT test result (71.4% vs 26.1%, P = 0.02). However, response to cholestyramine was also frequent in patients with a negative test result. CONCLUSIONS: The SeHCAT test accurately identifies patients with BAD who benefit from long-term cholestyramine treatment. Nevertheless, cholestyramine may be also effective in patients with chronic diarrhea but negative SeHCAT test result.

A Prospective Randomized Multicenter Study on the Impact of [18F]F-Choline PET/CT Versus Conventional Imaging for Staging Intermediate- to High-Risk Prostate Cancer.

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.

Can Baseline [18F]FDG PET/CT Predict Response to Immunotherapy After 6 Months and Overall Survival in Patients with Lung Cancer or Malignant Melanoma? A Multicenter Retrospective Study.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Materials and Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

ITA-IMMUNO-PET: The Role of [18F]FDG PET/CT for Assessing Response to Immunotherapy in Patients with Some Solid Tumors.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory.