Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade.

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus-myoclonus-ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%-25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.

Advanced oxidation protein products and malondialdehyde - the new biological markers of oxidative stress - are elevated in postmenopausal women.

OBJECTIVES: The aim of the study was to measure advanced oxidation protein products (AOPPs) as markers for oxidative stress to evaluate cardiovascular risk in pre- and postmenopausal women and to compare the results with malondialde-hyde (MDA) levels. MATERIAL AND METHODS: Twenty premenopausal women and 84 naturally postmenopausal patients were enrolled in the study. AOPP and MDA plasma levels were measured. The postmenopausal group was further subdivided into two groups: postmenopausal age of 40-49 and of 50-59 years. AOPP and MDA levels were compared between premenopausal, 40-49 and 50-59 year old menopausal women. RESULTS: Plasma AOPP and MDA levels in postmenopausal women were increased when compared with their premeno-pausal peers (123.83 ± 55.51 µmol/L vs. 61.59 ± 16.42 µmol/L and 6.50 ± 1.05 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). Mean plasma AOPP levels in the two menopausal age groups were both significantly higher from the premenopausal group (118.64 ± 59.1 µmol/L vs. 61.59 ± 16.42 µmol/L and 132.31 ± 48.97 µmol/L vs. 61.59 ± 16.42 µmol/L; respectively). No significant difference was found in mean AOPP levels between postmenopausal subjects of 40-49 and 50-59 years age (118.64 ± 59.12 µmol/L vs. 132.31 ± 48.97 µmol/L). Mean plasma MDA levels of each of two postmenopausal age groups were both significantly higher from the premenopausal group (6.50 ± 1.04 µmol/L vs. 5.98 ± 0.77 µmol/L and 6.50 ± 1.10 µmol/L vs. 5.98 ± 0.77 µmol/L; respectively). However, no statistically significant difference between the two postmenopausal age groups (6.50 ± 1.04 µmol/L vs. 6.50 ± 1.10 µmol/L) was found. CONCLUSIONS: AOPP and MDA levels are elevated in postmenopausal women as compared to their premenopausal peers, suggesting they can be used as markers for cardiovascular risk in postmenopausal women.

Integrated FDG-PET/CT contribution over cross-sectional imaging in recurrence or progression of pancreaticobiliary neoplasms.

PURPOSE: We aim to compare FDG-PET/CT and cross-sectional imaging (contrastenhanced CT/MRI) diagnostic abilities in detecting recurrence/progression of pancreaticobiliary system tumors and to reveal the clinical impact of integrated FDGPET/CT to CT/MRI on patient management. MATERIALS AND METHODS: FDG-PET/CT and CT/MRI scans of 70 patients from initiation of treatment until proven recurrence/progression were retrospectively evaluated. FDGPET/CT and contrast-enhanced CT/MRI accuracy, sensitivity, specificity, PPV and NPV are compared in terms of overall recurrence/progression diagnosis and sitespecific concern; local disease, local lymph node, and distant organ metastasis. The impact of integrated FDG-PET/CT on patient management is scrutinized. RESULTS: CT/MRI has higher sensitivity than FDG-PET/CT in detecting loco-regional involvement (90% vs 76.7% P: 0.152), local lymph node metastasis (88.9% vs 77.8%, P: 0.380) and distant organ metastasis (96.5% vs 80.7%; P: 0.006) in tumor recurrence/progression. In overall diagnosis, CT/MRI is more sensitive and accurate but less specific than FDG-PET/CT (92.3% vs 87.7%; 87.1% vs 84.2%; 40% vs 20%, respectively). In 8% (6/70) of patients FDG-PET/CT had a major impact on patient management. CONCLUSION: FDG-PET/CT and cross-sectional imaging have different advantages and shortcomings. In recurrence/progression, recognition of early changes is more feasible by CT/MRI. However, inconsistency of morphologic and metabolic findings is important reason of cross-sectional imaging failure. FDG-PET/CT is superior in showing extraabdominal metastases, but missing small-volume lesions and misinterpreting inflammatory changes are still a problem lowering its sensitivity. Nevertheless FDGPET/CT is good option for guiding undetermined imaging findings or clinic-radiologic mismatch.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

DLPF Targeted Repetitive Transcranial Magnetic Stimulation Improves Brain Glucose Metabolism Along with the Clinical and Electrophysiological Parameters in CBD Patients.

BACKGROUND: Corticobasal Degeneration (CBD) is a rare neurological disease caused by the pathological accumulation of tau protein. The primary pathological features of CBD include progressive neurodegenerative processes resulting in remarkable frontoparietal and basal ganglia atrophy. OBJECTIVE: Like in many other neurodegenerative disorders, there is still no effective disease-modifying drug therapy in CBD. Therefore, the development of new treatment methods is of great importance. In this study, we aimed to assess the stimulating effects of high-frequency DLPFC rTMS on the motor, cognitive and behavioral disturbances in four CBD patients. METHODS: Four (three females, one male) CBD patients who had been diagnosed as CBD were enrolled in this study. Patients were evaluated before and after the rTMS procedure regarding the motor, neuropsychometric and behavioral tests. The results of statistical analysis of behavioral and neuropsychometric evaluation were assessed via SPSS 18.0 package program. Data are expressed as mean, standard deviation. Before and after values of the groups were compared with the Wilcoxon sign rank test, and p<0.05 was considered significant. RESULTS: We have provided strong preliminary evidence that the improvement in clinical parameters was associated with the normalizations of the theta activity and glucose metabolism. CONCLUSION: Our current results are consistent with some previous trials showing a strong association between DLPFC targeted rTMS and electrophysiological normalizations in the left DLPFC.

The Role of 18F-FDG PET/CT in Predicting the Neoadjuvant Treatment Response in Patients with Locally Advanced Breast Cancer.

Purpose: Patients with locally advanced breast cancer (LABC) should be treated with neoadjuvant chemotherapy (NAC). Pathological complete response (pCR) is related to better disease-free survival (DFS). The best strategy for assessing the efficacy of NAC has not been established yet, but several studies have shown that 18F-FDG PET/CT is a potential imaging tool for assessing pCR. The aim of this study is to investigate the merits of 18F-FDG PET/CT imaging in predicting pCR in both axillary and breast tissue and to establish a threshold maximum standard uptake value (SUVmax) for predicting the response after completion of NAC. Methods: A total of 186 LABC patients, treated with an NAC regimen according to tumor subtype, were retrospectively analyzed in this study. All patients underwent 18F-FDG PET/CT imaging before and after completion of NAC. PET parameters were measured in the most FDG avid breast tissue and axillary lymph nodes. We analyzed the correlation between the tumor SUVmax of the PET/CT response and the pCR after surgery. DFS was also evaluated with respect to pCR. Results: Higher pCR rates were significantly associated with a higher tumor grade, an initial Ki-67 ≥20% (p = 0.03 and p = 0.003, respectively), a triple-negative subtype (32.9%), and a human epidermal growth factor receptor 2 (HER-2)-positive subtype (24.7%) (p < 0.001). There was a significant correlation between the pCR and a complete response in 18F-FDG PET/CT (p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT to determine the pCR after NAC were 100%, 72.2%, 85%, 75.2%, and 100%, respectively. We demonstrated a 1.1 cutoff SUVmax for breast tumors after NAC (OR: 3.94, 95% CI: 1.14-5.05, p = 0.004), the 18F-FDG PET/CT response to NAC (OR: 0.50, 95% CI: 0.25-0.99, p = 0.003), and the molecular subtype of breast tumors (OR: 0.58, 95% CI: 0.38-0.88, p = 0.011). Conclusion: Our results confirm that 18F-FDG PET/CT is a useful method for predicting the NAC response in LABC.

Isolated mucinous adrenal metastasis in a breast cancer patient.

Mucinous breast carcinoma (MBC) is a rare histological type of breast cancer and rarely associated with advanced disease. We report a case that had MBC with an isolated adrenal metastasis which was removed by laparoscopic adrenelectomy. This case is unique due to the unexpected metastasis of pure mucinous carcinoma developed after 4 years of hormone therapy.

Comparison of diagnostic performances of three different software packages in detecting coronary artery disease.

PURPOSE: Quantification of myocardial perfusion scintigraphy is frequently performed to assist physicians in detecting coronary artery disease (CAD). Software packages provide automated quantification of perfusion data. We aimed to compare the three commonly used software packages, Emory Cardiac Toolbox (ECT v2 and ECT v3), 4D-MSPECT (4DM v2 and 4DM v4) and Quantitative Perfusion SPECT (QPS v3 and QPS v4). METHODS: We selected 283 patients who had a myocardial perfusion scintigraphy with (201)Tl followed by coronary angiography within 3 months. Summed stress score (SSS), summed difference score (SDS), total stress defect extent (TDE) and regional stress defect extent values were obtained from programs. A ≥70% stenosis in coronary arteries and their major branches was considered positive for CAD. A subgroup of patients was used to form an institutional normal database for QPS and 4DM. Receiver-operating characteristic (ROC) analysis to detect CAD was performed. RESULTS: Mean SSS ± SD (vendor) for ECT v3, QPS v4 and 4DM v4 were 9.2 ± 7.1, 10.1 ± 6.8 and 5.5 ± 6.1, respectively. Area under the curve (AUC) values of SSS ROC analysis were 0.738 ± 0.031 for QPS v3, 0.755 ± 0.030 for QPS v4, 0.758 ± 0.030 for ECT v2, 0.778 ± 0.029 for ECT v3 and 0.771 ± 0.030 for 4DM v4. The AUC values for TDE were 0.755 ± 0.030 for QPS v4, 0.769 ± 0.030 for ECT v3 and 0.775 ± 0.029 for 4DM v4. The differences were not significant for both SSS and TDE. Differences of AUC between regional stress defect extent values of programs and AUC of SSS between institutional and vendor normal databases were not significant. CONCLUSION: The diagnostic performances of programs to detect CAD are similar. However, there are differences in the magnitudes of the quantitative values produced by the programs.

Virtual Reality Training Helpful in Motor and Cognition in Corticobasal Syndrome: A Case Report PET Study.

Corticobasal syndrome (CBS) is a rare progressive neurodegenerative disease characterized by a combination of asymmetric motor symptoms and non-motor symptoms. CBS is poorly responsive to levodopa. Non-pharmacological strategies have been found to be useful as components of a multidisciplinary therapeutic approach for patients with CBS. The purpose of this study was to investigate the effects of virtual reality training in addressing symptoms of CBS. A 64-year-old man was clinically diagnosed as CBS one year after the onset of complaints. Positron emission tomography (PET) scan showed asymmetrical hypometabolism in the right thalamus and basal ganglia. The patient was evaluated for balance, gait, mobility, and cognition 1 week before, 1 week after, and 1 year after 6 weeks of training, 3 times weekly (18 sessions in total). All clinical outcomes and PET result had improved after the intervention; cognition and balance were maintained after 1 year. Additionally, the asymmetric hypometabolism, which had been detectable on the PET scan, became normal, and a relative improvement was noted in the visual evaluation of cortical involvement. Virtual reality may address different aspects of motor and cognition and possibly brain metabolic changes that can affect the course of the disease in patients with CBS.

FDG-PET Scanning Shows Distributed Changes in Cortical Activity Associated with Visual Hallucinations in Eye Disease.

BACKGROUND AND OBJECTIVE: Charles Bonnet Syndrome (CBS) has been defined as complex visual hallucinations (CVH) due to visual loss. The underlying mechanism of CBS is not clear and the underlying pathophysiology of the visual hallucinations in CBS patients and pure visually impaired patients is still not clear. METHODS: In our study, we have scanned three patients with eye disease and CBS (VH+) and three patients with eye disease without CBS (VH-) using FDG-PET. RESULTS: Our results showed underactivity in the pons and overactivity in primary right left visual cortex and inferior parietal cortex in VH- patients and underactivity in left Broca, left inf frontal primary visual cortex and anterior and posterior cingulate cortex in VH+ patients relative to the normative 18FFDG PET data that was taken from the database consisting of 50 age-matched healthy adults without neuropsychiatric disorders. CONCLUSION: From this distributed pattern of activity changes, we conclude that the generation of visual hallucination in CBS is associated with bottom-up and top-down mechanism rather than the generally accepted visual deafferentation-related hyperexcitability theory.

Intense fluoro-2-deoxyglucose uptake in high-grade prostatic adenocarcinoma with negligible prostate-specific membrane antigen expression.

While 68Gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA) has demonstrated increasing utility in the evaluation of prostatic carcinoma, it is essential to be aware of false-negative findings. Further subtype analyses of prostate cancer will be helpful in the understanding of the underlying reasons. We herein present a high-grade prostate adenocarcinoma, with metastatic lesions showing high 18F-labeled fluoro-2-deoxyglucose uptake instead of 68Ga-PSMA.

Primary Ovarian Malignant Mixed Mullerian Tumour: A Case Report and Brief Review of Literature.

Malignant Mixed Mullerian Tumour of the Ovary (OMMMT), also referred to as carcinosarcoma is a very rare tumour accounting for less than 1% of all ovarian cancers. Due to the rarity of OMMMT, little is known about the disease course and outcome of women with these tumours. It is important to evaluate because of its aggressive behaviour with extremely unfavourable prognosis. These tumours are composed of both malignant epithelial and mesenchymal elements. Current data in the literature is still limited to small case series and case reports, therefore, its optimal treatment is somewhat controversial. In the current report, we introduce a case of OMMMT which was successfully treated with Platinum-based combination chemotherapy after optimal cytoreductive surgery. The clinical manifestations, pathologic characteristics, diagnosis and management of these tumours are reviewed here. Although the most effective treatment is currently unknown, optimal cytoreductive surgery and platinum-based chemotherapy appears to improve the outcomes. Despite the aggressive nature of this tumour and its poor response to the treatment, management works best when cancer is found early. The stage of the disease is the most important prognostic factor. Therefore, the crucial question is how to diagnose the cancer at earlier stages rather than seeking the optimal treatment.

Topiramate: A Novel Therapeutic Candidate for Diabetes and Aggression? Positron Emission Tomography (PET) Findings.

BACKGROUND: There is still limited knowledge regarding the role of impaired brain glucose metabolism in the generation of aggression during diabetes. Additionally, there are rapidly replicating piece of evidence suggesting that topiramate may exert significant mood stabilizing effect. In this respect, we aimed to evaluate the neurometabolic correlates of the therapeutic effect of topiramate in a patient with diabetes and Intermittent explosive disorder (IED). METHODS: We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts before and after treatment with topiramate. In order to reveal a defined information underlying the improvement of the aggressive symptoms we also combined the PET with Modified Overt Aggression Scale. RESULTS: We have found that topiramate leads to the improvement in Modified Overt Aggression Scale that was well correlated with the increase in cortical brain metabolism. DISCUSSION: The therapeutic role of topiramate may not only suggest secondary deficits due to diminished functions of the cortical part of emotional circuits but also indicate that diabetic individuals may be vulnerable to lower cerebral glucose metabolism in cortical regions. Further clinical trials that include well-conducted randomized controlled trials and cohort studies by using other methods (i.e., magnetic resonance spectroscopy and quantitative EEG analysis) are necessary to confirm our preliminary findings.

18F-FDG-PET Correlates of Impulse Control Disorder in a Diabetic Patient.

BACKGROUND: Studies have already shown that hyperglycemia and insulin resistance are significantly associated with the impairment of cerebral glucose metabolism that may secondary lead to cognitive disturbances. In this study, we aimed to evaluate the neurometabolic correlates of diabetes in a patient with Intermittent explosive disorder (IED). METHODS: We have investigated the cerebral glucose metabolism via 2-[18F]-fluoro-2- deoxy-D-glucose positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts. RESULTS: We have found significantly reduced glucose uptake in left temporoparietal region, pontin area, and left nucleus lentiformis. DISCUSSION: Our present results indicate decreased cerebral glucose metabolism in specific cerebral cortical and subcortical areas. The main limitation of this report is that, this is a single case study and that these findings need to be replicated in well- conducted randomized controlled studies by using additional neuroquantitative methods.

The Therapeutic Role of Lamotrigine And Topiramate In A Depressive Patient With Anxiety Symptoms And Cognitive Decline: Neurometabolic Correlates.

We describe here 67 years old women presented with symptoms of anxiety and cognitive impairment that responded well to the combined treatment of lamotrigine and topiramate. In contrast to recent data, we have shown that lamotrigine and topiramate treatment additively increased the cerebral glucose metabolism that was associated with complete resolution of the neuropsychiatric symptoms. Our findings indicate that the therapeutic effect of both agents involve a cortico-subcortical network and suggest the functional role of a bi-directional hippocampal-cingulate connectivity. The main limitation of this report is that this a single case study and that these findings need to be replicated in a larger sample e.g., as part of a controlled trial.

Significant contribution of Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in a case of acute lymphoblastic leukemia presenting with fever of unknown origin.

The diagnostic value of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has not been thoroughly evaluated in patients with leukemia. We herein report the case of a patient with B cell acute lymphoblastic leukemia (ALL) presenting with fever of unknown origin (FUO) who was diagnosed after FDG PET/CT indicated diffuse bone marrow involvement.

Endotracheal ectopic parathyroid adenoma mimicking asthma.

Primary benign tumors of the trachea are uncommon. These tumors may cause tracheal occlusion and lead to a misdiagnosis of asthma. Ectopic parathyroid adenoma (EPA) can be seen anywhere between the mandibular angle and the mediastinum. The distal part of the trachea is a rare location for EPA, and EPA obstructing the endotracheal lumen has not been reported in the literature. We herein describe a 52-year-old female with a several-year history of asthma treatment who presented with progressive dyspnea. Computed tomography revealed a mass that was obstructing the tracheal lumen. Total mass excision was performed via endobronchial treatment, and pathologic examination revealed EPA.

The nodal standard uptake value (SUV) as a prognostic factor in head and neck squamous cell cancer.

BACKGROUND/AIMS: The aim of present study is to evaluate the predictive and prognostic role of high [18F] fluoro-D-glucose (FDG) uptake of primary tumor and nodal metastasis in squamous cell carcinoma of head and neck (HNSCC). METHODOLOGY AND PATIENTS: Between February 2006 and July 2010, we retrospectively evaluated 64 patients with primary HNSCC in an institutional imaging trial. All patients who underwent evaluation pretreatment FDG-positron emission tomography/computarized tomography (FDG-PET/CT) imaging and 33 (51%) had pre- and after treatment FDG-PET/CT imaging. All treatments were performed with curative intent. Abnormal FDG uptakes were analyzed using maximum standardized uptake values (SUVm). The disease-free survival (DFS) and overall survival (OS) were evaluated with several prognostic factors such as pre-treatment SUVm and %change in SUVm. RESULTS: Tumor sites are nasopharynx (n=29, 45.3%), larynx (n=16, 25%), oropharynx (n=13, 20.4%) and hypopharynx (n=6, 9.4%). Median age was 58 (range: 16-87) and most patients (84.4%) had stage III/IV lesions. Objective response rate was 78.2%. The median primary tumor SUVm was 13.4 (range, 4.8-33.1), median nodal SUVm was 4.45 (range, 0-25.6) and median % change in SUVm was 74.1 (range, -61-100). On multivariate analysis, nodal SUVm and surgery remained significant predictors of DFS. There was no statistical significance found between survival and other factors. CONCLUSIONS: We have found that while nodal SUVm is prognostic for DFS, primary tumor SUVm and % change in SUVm are not.