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Reproductive Sciences (Thousand Oaks,... May 2024Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the... (Review)
Review
Adenomyosis is associated with dysmenorrhea and chronic pelvic pain; however, the triggering mechanisms of painful stimuli and the role of uterine nerve fibers in the manifestation of pain remain poorly understood. The objective of this study was to systematically review the role of uterine nerve fibers' presence and density in the occurrence of pain in patients with adenomyosis. An electronic search was performed using the Embase, PubMed/Medline, and Cochrane databases. We included all studies from inception to November 2023. A total of ten studies that compared uterine biopsies samples of women with and without adenomyosis were included. The biomarker antiprotein gene product 9.5 was decreased or absent in the endometrium of most included women with adenomyosis. None of the included studies observed a difference in neurofilament (NF) staining between the adenomyosis and non-adenomyosis groups. Studies that assessed nerve growth factor (NGF) staining were heterogeneous in design. One study reported no difference in immunohistochemistry staining in any endometrial layer between the adenomyosis and non-adenomyosis groups, while another reported increased staining in the adenomyosis functional endometrial layer, and a third study reported overexpression of NGF, synaptophysin (SYN), and microtubule-associated protein 2 mRNA in focal adenomyosis alone. Preliminary data from poor-quality studies suggest an increase in the uterine density of nerve fibers in patients with adenomyosis. Well-designed studies are essential to assess the cause-and-effect relationship between uterine nerve fibers and pain in patients with adenomyosis.
PubMed: 38720155
DOI: 10.1007/s43032-024-01587-8 -
Frontiers in Psychiatry 2023Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This... (Review)
Review
BACKGROUND
Ketamine and psychedelics have abuse liability. They can also induce "transformative experiences" where individuals experience enhanced states of awareness. This enhanced awareness can lead to changes in preexisting behavioral patterns which could be beneficial in the treatment of substance use disorders (SUDs). Preclinical and clinical studies suggest that ketamine and psychedelics may alter markers associated with synaptic density, and that these changes may underlie effects such as sensitization, conditioned place preference, drug self-administration, and verbal memory performance. In this scoping review, we examined studies that measured synaptic markers in animals and humans after exposure to ketamine and/or psychedelics.
METHODS
A systematic search was conducted following PRISMA guidelines, through PubMed, EBSCO, Scopus, and Web of Science, based on a published protocol (Open Science Framework, DOI: 10.17605/OSF.IO/43FQ9). Both and studies were included. Studies on the following synaptic markers were included: dendritic structural changes, PSD-95, synapsin-1, synaptophysin-1, synaptotagmin-1, and SV2A.
RESULTS
Eighty-four studies were included in the final analyses. Seventy-one studies examined synaptic markers following ketamine treatment, nine examined psychedelics, and four examined both. Psychedelics included psilocybin/psilocin, lysergic acid diethylamide, N,N-dimethyltryptamine, 2,5-dimethoxy-4-iodoamphetamine, and ibogaine/noribogaine. Mixed findings regarding synaptic changes in the hippocampus and prefrontal cortex (PFC) have been reported when ketamine was administered in a single dose under basal conditions. Similar mixed findings were seen under basal conditions in studies that used repeated administration of ketamine. However, studies that examined animals during stressful conditions found that a single dose of ketamine counteracted stress-related reductions in synaptic markers in the hippocampus and PFC. Repeated administration of ketamine also counteracted stress effects in the hippocampus. Psychedelics generally increased synaptic markers, but results were more consistently positive for certain agents.
CONCLUSION
Ketamine and psychedelics can increase synaptic markers under certain conditions. Heterogeneous findings may relate to methodological differences, agents administered (or different formulations of the same agent), sex, and type of markers. Future studies could address seemingly mixed results by using meta-analytical approaches or study designs that more fully consider individual differences.
PubMed: 37435405
DOI: 10.3389/fpsyt.2023.1197890 -
Folia Medica Cracoviensia Apr 2023Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of...
Carcinoma of unknown primary (CUP) is a heterogeneous group of oncological diseases in which it is impossible to determine the primary tumor. The incidence is 3-5% of oncologic patients, but the survival time varies from 6 weeks to 5 months. The diagnostics should begin with a clinical evaluation and basic laboratory tests. For CUP placed in head and neck the positron emission tomography - computed tomography is recommended; pancreatic or lung neoplasms are diagnosed with the computed tomography as well. Recently, the magnetic resonance, especially whole-body diffusion-weighted imaging has been introduced to the imaging panel. The lesion obtained during surgically removed metastases or biopsy material should be histopathological and molecularly examined to define the type of tumor. The basic immunoexpression panel should include cytokeratin-5/6, -7 and -20, EMA, synaptophysin, chromogranin, vimentin and GATA3 and molecular expression of ERBB2, PIK3CA, NF1, NF2, BRAF, IDH1, PTEN, FGFR2, EGFR, MET and CDK6. During the accurate diagnostics enable to classify malignancy of undefined primary origin as provisional CUP or finally confirmed CUP in which the primary place of tumor remains undetectable. The detailed diagnostics should be performed in highly specified centers to establish an accurate diagnosis and to initiate personalized treatment. Majority of patients are diagnosed with adenocarcinoma (70%), undifferentiated carcinoma (20%), squamous cell or transitional cell/uroepithelial carcinoma (5-10%), neuroendocrine tumor (5%) and with minor incidence other histological types, including melanoma.
Topics: Humans; Neoplasms, Unknown Primary; Carcinoma; Adenocarcinoma; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Head and Neck Neoplasms
PubMed: 37406274
DOI: 10.24425/fmc.2023.145427 -
Pediatric Ectopic Cushing Syndrome Caused by Hepatic Neoplasms: A Case Report and Systematic Review.Cureus Mar 2023Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an...
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is rare in children, and localizing the source of EAS is often challenging. Here, we report EAS in an adolescent boy who presented with Cushingoid features and had endogenous ACTH-dependent hypercortisolism on hormonal evaluation. Abdominal ultrasound and CT revealed a hepatic lesion with characteristics suggestive of hemangioma, whereas the lesion was tracer non-avid on Ga-DOTANOC positron emission tomography/CT. A regional sampling of ACTH was done to confirm the hepatic lesion as the source of EAS, and a definitive ACTH gradient was observed between the hepatic vein and the right internal jugular vein. Further, a preoperative biopsy of the lesion revealed a small round cell tumor with positive immunostaining for ACTH and synaptophysin, suggestive of a neuroendocrine tumor. The patient was managed with partial hepatectomy, resulting in hormonal and clinical remission of Cushing syndrome. In a systematic review of pediatric EAS due to primary hepatic tumors (n = 11), calcifying nested stromal epithelial cell tumors were the most common. EAS-associated hepatic tumors were larger (≥10 cm) except benign primary hepatic neuroendocrine tumors (PHNET). The latter were misdiagnosed as hemangioma in two cases by anatomical imaging but correctly diagnosed by somatostatin receptor scintigraphy. Hepatic tumors causing EAS in children required extensive resection, except benign PHNET. Nevertheless, all benign tumors with an uncomplicated perioperative course demonstrated disease-free survival over a median follow-up period of two years.
PubMed: 37123777
DOI: 10.7759/cureus.36852 -
Seminars in Oncology Dec 2022The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a... (Review)
Review
Synchronous or metachronous presentation of pancreatic neuroendocrine tumor versus secondary lesion to pancreas in patients affected by renal cell carcinoma. Systematic review.
The simultaneous or metachronous occurrence of pancreatic neuroendocrine tumor (panNET) and renal cell carcinoma (RCC) may represent a rare coincidence or a manifestation of von Hippel-Lindau disease (VHL). These two malignancies share both radiological and cytopathological features, making the differential diagnosis very challenging. In this review, we collected all cases of concurrent diagnosis of localized panNET and RCC, with or without VHL, as reported in the literature to date. We aimed to provide an insight into the differential diagnosis between panNET and RCC pancreatic metastasis with a focus on the optimal therapeutic algorithm depending on the diagnosis. We performed literature research in PubMed library databases for articles about coexisting panNET and RCC published from 2001 to 2018. We selected nine articles with a total of 13 patients, including one treated at our institution. Patients' median age was 49 years and eight out of 13 patients were women. VHL was diagnosed in nine cases. Most patients underwent radical nephrectomy for RCC (9/13) and a clear cell renal carcinoma variant was identified in six cases. The diagnosis of panNET was synchronous with RCC detection in nine cases and metachronous in four cases. The diameter of the pancreatic lesion was >2 cm in six cases. In two cases the panNET was misdiagnosed as metastatic RCC by radiological tests. Somatostatin receptor scanning was performed only in our patient (Octreoscan) showing intense uptake in the pancreatic mass. Endoscopic ultrasound fine needle aspiration of the pancreatic lesion was performed in four patients: in two cases the panNET was confused with metastatic RCC by cytological analysis. Most patients underwent pancreatic surgery (10/13) without histological confirmation. Clear cell panNET was recognized in six cases, while mixed neuroendocrine non-neuroendocrine neoplasm was diagnosed in one patient. Immunohistochemistry (IHC) staining showed positivity to typical neuroendocrine markers (chromogranin A and synaptophysin) in all reported tested cases (8/8). Three patients underwent systemic treatment: two patients received sunitinib and one patient interleukin-2 (IL-2). Other neoplasms were observed in seven patients, of whom six were affected by VHL syndrome. When neoplastic lesions are recognized in both the kidney and pancreas, panNET and RCC pancreatic metastasis are often misdiagnosed due to similar radiological and cytopathological features. An accurate differential diagnosis is crucial and IHC plays a central role in distinguishing the two entities. The therapeutic algorithm may change depending on the diagnosis: while pancreatic RCC metastases benefit from resection, in panNETs and VHL the indication for surgery must be carefully evaluated.
Topics: Humans; Female; Middle Aged; Male; Carcinoma, Renal Cell; Kidney Neoplasms; Neuroendocrine Tumors; Pancreatic Neoplasms; Pancreas; von Hippel-Lindau Disease
PubMed: 36759234
DOI: 10.1053/j.seminoncol.2023.01.007 -
Diagnostic Cytopathology Jun 2023Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies.
BACKGROUND
Solid-papillary carcinoma (SPC) of the breast is a rare variant of low-grade in situ and invasive carcinoma but there are only a few of the cytologic studies.
METHODS
We examined 44 cases of SPC of the breast to define the cytologic features. We also made a systemic review of reported cases of SPC and neuroendocrine tumor (NET) of the breast.
RESULTS
Both of our and the reviewed cases with SPC were very similar in the cytologic finding. It included hypercellularity, highly discohesive clusters, numerous isolated cells, small nuclei, finely granular chromatin of salt-and-pepper appearance, inconspicuous nucleoli, low nuclear-cytoplasmic ratio, and a plasmacytoid appearance. Moreover, SPC and NET had frequently all of these features in common. Capillary vessels structures and mucinous substance were not frequently seen in our and the reviewed cases with SPC. Rosette and pseudorosette were very rare in the cytologic specimen. The immunocytochemistry with our 9 cases with SPC indicated diffuse positivity for chromogranin A and/or synaptophysin.
CONCLUSION
Many cytologic features are frequently shared by SPC and NET of the breast. However, the vascular structure may not be a precise criterion for SPC. Rosette and pseudorosette are rarely helpful for the cytologic diagnosis.
Topics: Female; Humans; Breast; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Neuroendocrine; Carcinoma, Papillary; Neuroendocrine Tumors
PubMed: 36748676
DOI: 10.1002/dc.25112 -
Journal of Gastrointestinal and Liver... Dec 2022Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von...
BACKGROUND AND AIMS
Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von Recklinghausen's disease. The aims of this study were to systematically review the literature regarding SAV and to highlight the clinicopathological characteristics and optimal therapeutic management of this rare entity.
METHODS
A systematic search of the literature in PubMed/Medline and Scopus databases was performed by two independent investigators, including all case reports and case series concerning SAVs from 1980 until September 2021.
RESULTS
In total, 37 articles were retrieved, including 43 patients, with a male to female ratio of 1.8:1 and a mean age of 46.8 ± 11.3 years (mean, SD). For 23 out of 43 patients (53.5%), Von Recklinghausen's disease was proved. The main clinical manifestations were abdominal pain (41.9%), jaundice (27.9%), weight loss (20.9%) and bowel disorders (20.9%). Typical histological findings included psammoma bodies, nests or clusters of epithelial cells with eosinophilic cytoplasm, while somatostatin staining was positive in 35 patients (81.4%), chromogranin-A in 21 patients (48.8%) and synaptophysin in 18 patients (41.9%). Surgery was the initial therapeutic approach in 34 patients (79.1%), whereas Whipple's procedure was the preferred surgical approach in 23 patients (53.4%). The longest survival among included patients was 13 years and only two postoperative deaths (4.7%) were reported.
CONCLUSIONS
Somatostatinomas of the ampulla of Vater are rare malignancies that require increased physicians' suspicion and accurate surgical approach in order to achieve optimal therapeutic results.
Topics: Humans; Male; Female; Adult; Middle Aged; Somatostatinoma; Neurofibromatosis 1; Ampulla of Vater; Duodenal Neoplasms; Pancreatic Neoplasms
PubMed: 36535044
DOI: 10.15403/jgld-4383 -
Frontiers in Endocrinology 2022Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a...
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Carcinoma, Neuroendocrine; Adenocarcinoma; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 36440195
DOI: 10.3389/fendo.2022.1012005 -
Journal of Geriatric Psychiatry and... Jul 2023Accurately diagnosing neurodegenerative dementia is often challenging due to overlapping clinical features. Disease specific biomarkers could enhance diagnostic... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Accurately diagnosing neurodegenerative dementia is often challenging due to overlapping clinical features. Disease specific biomarkers could enhance diagnostic accuracy. However, CSF analysis procedures and advanced imaging modalities are either invasive or high-priced, and routinely unavailable. Easily accessible disease biomarkers would be of utmost value for accurate differential diagnosis of dementia subtypes.
OBJECTIVE
To assess the diagnostic accuracy of blood-based biomarkers for the differential diagnosis of AD from Frontotemporal Lobar Degeneration (FTLD), or AD from Dementia with Lewy Bodies (DLB).
METHODS
Systematic review. Three databases (PubMed, Scopus, and Web of Science) were searched. Studies assessing blood-based biomarkers levels in AD versus FTLD, or AD versus DLB, and its diagnostic accuracy, were selected. When the same biomarker was assessed in three or more studies, a meta-analysis was performed. QUADAS-2 criteria were used for quality assessment.
RESULTS
Twenty studies were included in this analysis. Collectively, 905 AD patients were compared to 1262 FTLD patients, and 209 AD patients were compared to 246 DLB patients. Regarding biomarkers for AD versus FTLD, excellent discriminative accuracy (AUC >0.9) was found for p-tau181, p-tau217, synaptophysin, synaptopodin, GAP43 and calmodulin. Other biomarkers also demonstrated good accuracy (AUC = 0.8-0.9). For AD versus DLB distinction, only miR-21-5p and miR-451a achieved excellent accuracy (AUC >0.9).
CONCLUSION
Encouraging results were found for several biomarkers, alone or in combination. Prospective longitudinal designs and consensual protocols, comprising larger cohorts and homogeneous testing modalities across centres, are essential to validate the clinical value of blood biomarkers for the precise etiological diagnosis of dementia.
Topics: Humans; Alzheimer Disease; tau Proteins; Amyloid beta-Peptides; Prospective Studies; Frontotemporal Lobar Degeneration; Frontotemporal Dementia; Diagnosis, Differential; Biomarkers; MicroRNAs; Lewy Body Disease
PubMed: 36423207
DOI: 10.1177/08919887221141651 -
Molecular Psychiatry Mar 2022The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and... (Meta-Analysis)
Meta-Analysis
The pathophysiological mechanisms underlying bipolar (BD) and major depressive disorders (MDD) are multifactorial but likely involve synaptic dysfunction and dysregulation. There are multiple synaptic proteins but three synaptic proteins, namely SNAP-25, PSD-95, and synaptophysin, have been widely studied for their role in synaptic function in human brain postmortem studies in BD and MDD. These studies have yielded contradictory results, possibly due to the small sample size and sourcing material from different cortical regions of the brain. We performed a systematic review and meta-analysis to understand the role of these three synaptic proteins and other synaptic proteins, messenger RNA (mRNA) and their regional localizations in BD and MDD. A systematic literature search was conducted and the review is reported in accordance with the MOOSE Guidelines. Meta-analysis was performed to compare synaptic marker levels between BD/MDD groups and controls separately. 1811 papers were identified in the literature search and screened against the preset inclusion and exclusion criteria. A total of 72 studies were screened in the full text, of which 47 were identified as eligible to be included in the systematic review. 24 of these 47 papers were included in the meta-analysis. The meta-analysis indicated that SNAP-25 protein levels were significantly lower in BD. On average, PSD-95 mRNA levels were lower in BD, and protein levels of SNAP-25, PSD-95, and syntaxin were lower in MDD. Localization analysis showed decreased levels of PSD-95 protein in the frontal cortex. We found specific alterations in synaptic proteins and RNAs in both BD and MDD. The review was prospectively registered online in PROSPERO international prospective register of systematic reviews, registration no. CRD42020196932.
Topics: Bipolar Disorder; Brain; Depressive Disorder, Major; Disks Large Homolog 4 Protein; Humans; Mood Disorders; RNA, Messenger
PubMed: 35022529
DOI: 10.1038/s41380-021-01410-9