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Journal of Nuclear Medicine : Official... Jan 2024Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are grossly visible (typically > 5 mm) intraductal epithelial neoplasms of mucin-producing cells, arising...
Immunohistochemical FAP Expression Reflects Ga-FAPI PET Imaging Properties of Low- and High-Grade Intraductal Papillary Mucinous Neoplasms and Pancreatic Ductal Adenocarcinoma.
Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are grossly visible (typically > 5 mm) intraductal epithelial neoplasms of mucin-producing cells, arising in the main pancreatic duct or its branches. According to the current 2-tiered grading scheme, these lesions are categorized as having either low-grade (LG) dysplasia, which has a benign prognosis, or high-grade (HG) dysplasia, which formally represents a carcinoma in situ and thus can transform to pancreatic ductal adenocarcinoma (PDAC). Because both entities require different treatments according to their risk of becoming malignant, a precise pretherapeutic diagnostic differentiation is inevitable for adequate patient management. Recently, our group has demonstrated that Ga-fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT shows great potential for the differentiation of LG IPMNs, HG IPMNs, and PDAC according to marked differences in signal intensity and tracer dynamics. The purpose of this study was to biologically validate FAP as a target for PET imaging by analyzing immunohistochemical FAP expression in LG IPMNs, HG IPMNs, and PDAC and comparing with SUV and time to peak (TTP) measured in our prior study. To evaluate the correlation of the expression level of FAP and α-smooth muscle actin (αSMA) in neoplasm-associated stroma depending on the degree of dysplasia in IPMNs, 98 patients with a diagnosis of LG IPMN, HG IPMN, PDAC with associated HG IPMN, or PDAC who underwent pancreatic surgery at the University Hospital Heidelberg between 2017 and 2023 were identified using the database of the Institute of Pathology, University Hospital Heidelberg. In a reevaluation of hematoxylin- and eosin-stained tissue sections of formalin-fixed and paraffin-embedded resection material from the archive, which was originally generated for histopathologic routine diagnostics, a regrading of IPMNs was performed by a pathologist according to the current 2-tiered grading scheme, consequently eliminating the former diagnosis of "IPMN with intermediate-grade dysplasia." For each case, semithin tissue sections of 3 paraffin blocks containing neoplasm were immunohistologically stained with antibodies directed against FAP and αSMA. In a masked approach, a semiquantitative analysis of the immunohistochemically stained slides was finally performed by a pathologist by adapting the immunoreactive score (IRS) and human epidermal growth factor receptor 2 (Her2)/neu score to determine the intensity and percentage of FAP- and αSMA-positive cells. Afterward, the IRS of 14 patients who underwent Ga-FAPI-74 PET/CT in our previous study was compared with their SUV, SUV, and TTP for result validation. From 98 patients, 294 specimens (3 replicates per patient) were immunohistochemically stained for FAP and αSMA. Twenty-three patients had LG IPMNs, 11 had HG IPMNs, 10 had HG IPMNs plus PDAC, and 54 had PDAC. The tumor stroma was in all cases variably positive for FAP. The staining intensity, percentage of FAP-positive stroma, IRS, and Her2/neu score increased with higher malignancy. αSMA expression could be shown in normal pancreatic stroma as well as within peri- and intraneoplastic desmoplastic reaction. No homogeneous increase in intensity, percentage, IRS, and Her2/neu score with higher malignancy was observed for αSMA. The comparison of the mean IRS of FAP with the mean SUV, SUV, and TTP of Ga-GAPI-74 PET/CT showed a matching value increasing with higher malignancy in Ga-FAPI-74 PET imaging and immunohistochemical FAP expression. The immunohistochemical staining of IPMNs and PDAC validates FAP as a biology-based stromal target for in vivo imaging. Increasing expression of FAP in lesions with a higher degree of malignancy matches the expectation of a stronger FAP expression in PDAC and HG IPMNs than in LG IPMNs and corroborates our previous findings of higher SUVs and a longer TTP in PDAC and HG IPMNs than in LG IPMNs.
Topics: Humans; Gallium Radioisotopes; Pancreatic Intraductal Neoplasms; Positron Emission Tomography Computed Tomography; Adenocarcinoma, Mucinous; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreatic Ducts; Positron-Emission Tomography
PubMed: 38167622
DOI: 10.2967/jnumed.123.266393 -
Catheterization and Cardiovascular... Jul 2023Papillary muscle rupture (PMR) is a rare complication of acute myocardial infarction (AMI) associated with high mortality and morbidity. Surgery is the gold-standard... (Review)
Review
Papillary muscle rupture (PMR) is a rare complication of acute myocardial infarction (AMI) associated with high mortality and morbidity. Surgery is the gold-standard treatment for these patients, but it is burdened by a high perioperative risk due to hemodynamic instability. Mitral transcatheter edge-to-edge repair (M-TEER) was reported to be safe and effective in unstable patients with significant mitral regurgitation. However, data in patients with post-AMI PMR are limited to a few case reports. In this review, we summarized all data available regarding percutaneous treatment of post-AMI PMR. These results show that M-TEER is safe and effective in this setting with low in-hospital mortality and complications and high rate of significant mitral regurgitation reduction.
Topics: Humans; Mitral Valve Insufficiency; Mitral Valve; Papillary Muscles; Heart Rupture, Post-Infarction; Treatment Outcome; Myocardial Infarction; Heart Valve Prosthesis Implantation; Heart Failure
PubMed: 37161909
DOI: 10.1002/ccd.30682 -
Methods in Molecular Biology (Clifton,... 2024Urinary bladder cancer is the tenth most common cancer worldwide with high morbidity and mortality. The majority of bladder cancers are urothelial carcinomas. More than...
Urinary bladder cancer is the tenth most common cancer worldwide with high morbidity and mortality. The majority of bladder cancers are urothelial carcinomas. More than half are papillomas or the papillary urothelial carcinomas (stages Ta and T1), which have a relatively good prognosis. Squamous cell carcinomas have a variable survival rate, while carcinomas in situ (Tis) can progress to muscle-invasive urothelial carcinomas (T2) with a poor prognosis. The most challenging feature of bladder cancer is its high recurrence rate, ranging from 50% to 90% of cases. The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model is an invaluable experimental tool for bladder cancer research, as BBN-induced bladder cancer in rodents resembles human bladder cancer in its morphological, biological, and molecular features. We present here a detailed protocol for the treatment of mice and the main expected results.
Topics: Humans; Nitrosamines; Urinary Bladder Neoplasms; Urinary Bladder; Carcinoma, Squamous Cell; Muscles
PubMed: 38236533
DOI: 10.1007/978-1-0716-3714-2_3 -
Head and Neck Pathology Jun 2024The aim of the study is to investigate the immunohistochemical expression of both Alpha smooth muscle actin and Transforming Growth Factor beta and compare their... (Comparative Study)
Comparative Study
PURPOSE
The aim of the study is to investigate the immunohistochemical expression of both Alpha smooth muscle actin and Transforming Growth Factor beta and compare their expression in oral papillary squamous cell carcinoma with their expression in different histological grades of oral squamous cell carcinoma. A correlation between these immuno-histochemical expressions and histological findings will then be performed. The research question is "Do the percentages of α-SMA and TGF-β immune-expression in OPSCC differ from that in the conventional OSCC?".
METHODS
This will be achieved by collecting archival blocks of oral papillary squamous cell carcinoma and different grades of oral squamous cell carcinoma, staining the specimens with Transforming Growth Factor beta and alpha smooth muscle actin, then measuring the mean staining index of expression in each group and the area percent of both markers.
RESULTS
Results revealed that transforming growth factor beta expression in the epithelium was high in all cases of well-differentiated squamous cell carcinoma, most oral papillary squamous cell carcinoma, and poorly differentiated oral squamous cell carcinoma. On the other hand, different grades of oral squamous cell carcinoma showed a high staining index of alpha smooth muscle actin expression in the stroma. While cases of oral papillary squamous cell carcinoma were either moderate or low-staining.
CONCLUSIONS
Oral papillary squamous cell carcinoma has a favourable prognosis compared to different histological grades, and the prognosis does not depend only on histological grade but also on other prognostic factors.
Topics: Humans; Mouth Neoplasms; Immunohistochemistry; Actins; Biomarkers, Tumor; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Transforming Growth Factor beta; Male; Female
PubMed: 38884825
DOI: 10.1007/s12105-024-01635-4 -
Heart Rhythm Oct 2023Ventricular arrhythmias (VAs) originating from papillary muscles (PAPs) can be challenging when targeted with catheter ablation. Reasons may include premature...
BACKGROUND
Ventricular arrhythmias (VAs) originating from papillary muscles (PAPs) can be challenging when targeted with catheter ablation. Reasons may include premature ventricular complex pleomorphism, structurally abnormal PAPs, or unusual origins of VAs from PAP-myocardial connections (PAP-MYCs).
OBJECTIVE
The purpose of this study was to correlate PAP anatomy with mapping and ablation of PAP VAs.
METHODS
In a series of 43 consecutive patients with frequent PAP arrhythmias referred for ablation, the anatomy and structure of PAPs and VA origins were analyzed using multimodality imaging. Successful ablation sites were analyzed for location on the PAP body or a PAP-MYC.
RESULTS
In a total of 17 of 43 patients (40%), VAs originated from a PAP-MYC (in 5 of 17 patients, the PAP inserted into the mitral valve anulus); and in 41 patients, VAs originated from a PAP body. VAs from a PAP-MYC more often had delayed R-wave transition than did other PAP VAs (69% vs 28%; P < .001). Patients with failed procedures had more PAP-MYCs (24.8 ± 8 PAP-MYCs per patient vs 16 ± 7 PAP-MYCs per patient; P < .001).
CONCLUSION
Multimodality imaging identifies anatomic details of PAPs that facilitate mapping and ablation of VAs. In more than a third of patients with PAP VAs, VAs originate from connections between PAPs and the surrounding myocardium or between other PAPs. VA electrocardiographic morphologies are different when VAs originate from PAP-connection sites as compared with VAs originating from the PAP body.
Topics: Humans; Papillary Muscles; Tachycardia, Ventricular; Ventricular Premature Complexes; Electrocardiography; Mitral Valve; Catheter Ablation; Heart Ventricles
PubMed: 37329938
DOI: 10.1016/j.hrthm.2023.06.009 -
Heart Rhythm Oct 2023
Topics: Humans; Ventricular Premature Complexes; Papillary Muscles; Heart Ventricles; Echocardiography
PubMed: 37451497
DOI: 10.1016/j.hrthm.2023.07.006 -
European Heart Journal. Cardiovascular... Feb 2024Mitral valve prolapse (MVP) is usually regarded as a benign condition though the proportion of patients with a life-threatening arrhythmic MVP form remains undefined.... (Review)
Review
Mitral valve prolapse (MVP) is usually regarded as a benign condition though the proportion of patients with a life-threatening arrhythmic MVP form remains undefined. Recently, an experts' consensus statement on arrhythmic MVP has proposed approaches for risk stratification across the spectrum of clinical manifestation. However, sudden cardiac death may be the first presentation, making clinicians focused to early unmasking this subset of asymptomatic patients. Growing evidence on the role of cardiac imaging in the in-deep stratification pathway has emerged in the last decade. Pathology findings have suggested the fibrosis of papillary muscles and inferobasal left ventricular wall as the malignant hallmark. Cardiac magnetic resonance, while of limited availability, allows the identification of this arrhythmogenic substrate. Therefore, speckle-tracking echocardiography may be a gateway to prompt referring patients to further advanced imaging investigation. Our review aims to summarize the phenotypic features linked to the arrhythmic risk and to propose an image-based algorithm intended to help stratifying asymptomatic MVP patients.
Topics: Humans; Mitral Valve Prolapse; Algorithms; Consensus; Death, Sudden, Cardiac; Papillary Muscles
PubMed: 38061000
DOI: 10.1093/ehjci/jead332 -
Journal of Medical Case Reports Aug 2023Endomyocardial fibrosis is a grim disease. It is the most common restrictive cardiomyopathy worldwide, but the exact etiology and pathogenesis both remain unknown....
BACKGROUND
Endomyocardial fibrosis is a grim disease. It is the most common restrictive cardiomyopathy worldwide, but the exact etiology and pathogenesis both remain unknown. Endomyocardial fibrosis is recurrently associated with chronic eosinophilia and probable dietary, environmental, and infectious factors, which contribute not only to the onset of the disease (an inflammatory process) but also to its progression and maintenance (endomyocardial damage and scar formation). The trademark of the disease is the fibrotic obliteration of the affected ventricle. The combination of such processes produces focal or diffuse endocardial thickening and fibrosis, which leads to restrictive physiology. Endomyocardial fibrosis affects the apices of the right and the left ventricle in around 50% of cases and most often extends to the posterior leaflet of the mitral valve. Sometimes it involves the papillary muscle and chordae tendineae, causing atrioventricular valve dysfunction. The fibrosis does not affect extracardiac organs. This cardiomyopathy is most recurrent in tropical areas of the world.
CASE PRESENTATION
A 67-year-old Black male with past medical history of schistosomiasis infection in childhood presented with progressive dyspnea, lower extremity edema, and weakness for 2 years. He was diagnosed with endomyocardial fibrosis. The echocardiogram showed an increased thickness in the septum (17 mm) and free left ventricular wall (15 mm), obliteration of the left ventricular apex and inflow tract, and mitral valve regurgitation. Cardiac magnetic resonance imaging revealed apical left ventricle wall thickening with left ventricular apical obliteration associated with enlargement of the respective atrium. Delayed enhancement imaging showed endomyocardium enhancement involving left ventricular apex, mitral valve regurgitation due to annulus dilation, and a thrombus at left ventricular apex. He underwent open heart surgery with mitral valve replacement, endocardial decortication, endomyocardiectomy, and two-vessel coronary artery bypass grafting as preoperative coronary angiogram showed mild right coronary artery and proximal left anterior descending artery severe lesions. Postoperative course was uncomplicated, and he was discharged successfully from the hospital. Six months after surgery, he was New York Heart Association functional class I.
CONCLUSION
The purpose of this case report is to illustrate the aspects of endomyocardial fibrosis by reporting a case of this entity. In conclusion, progress in imaging techniques and treatment in a reference institution for cardiac diseases contribute to earlier diagnosis and survival in patients with endomyocardial fibrosis.
Topics: Humans; Male; Aged; Endomyocardial Fibrosis; Heart Ventricles; Mitral Valve Insufficiency; Myocardium; Fibrosis
PubMed: 37568222
DOI: 10.1186/s13256-023-04056-z -
Interdisciplinary Cardiovascular and... Dec 2023Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal...
OBJECTIVES
Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs.
METHODS
The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years.
RESULTS
A non-significant increase in MCs was observed [odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.57; P = 0.364], with stronger growth in ventricular septal rupture diagnoses (OR = 1.43, 95% CI 0.95-2.18; P = 0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR = 2.47, 95% CI 1.24-4.92; P = 0.010), more stable conditions (OR = 2.61, 95% CI 1.27-5.35; P = 0.009) and higher EuroSCORE II (OR = 1.04, 95% CI 1.01-1.06; P = 0.006).
CONCLUSIONS
A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality.
PubMed: 38109676
DOI: 10.1093/icvts/ivad198 -
Research Square Nov 2023The use of frozen and cryo-sectioned cardiac muscle preparations, introduced recently by (Feng & Jin, 2020), offers promising advantages of easy transport and exchange...
The use of frozen and cryo-sectioned cardiac muscle preparations, introduced recently by (Feng & Jin, 2020), offers promising advantages of easy transport and exchange of muscle samples among collaborating laboratories. In this report, we examined integrity of such preparation by studying tension transients in response to sinusoidal length changes and following concomitant amplitude and phase shift in tension time courses at varying frequencies. We used sections with 70 μm thickness, isolated fiber preparations, and studied cross-bridge (CB) kinetics: we activated the preparations with saturating Ca, and varying concentrations of ATP and phosphate (Pi). Our experiments have demonstrated that this preparation has the normal active tension and elementary steps of the CB cycle. Furthermore, we investigated the effect of Ca on the rate constants and found that the rate constant of the force generation step is proportionate to [Ca] when it is <5 μM. This observation suggests that the activation mechanism can be described by a simple second order reaction. As expected, we found that magnitude parameters including tension and stiffness are related to [Ca] by the Hill equation with cooperativity of 4-5, consistent to the fact that Ca activation mechanisms involve cooperative multimolecular interactions. Our results are consistent with a long-held hypothesis that process C (phase 2 of step analysis) represents the CB detachment step, and process B (phase 3) represents the force generation step. In this report, we further found that constant may also represent work performance step. Our experiments have demonstrated excellent CB kinetics with reduced noise and well-defined two exponentials, which are better than skinned fibers, and easier to handle and study than single myofibrils.
PubMed: 37961283
DOI: 10.21203/rs.3.rs-3516486/v1