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Modern Pathology : An Official Journal... Jun 2024Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or...
Nephrogenic adenoma is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with an antecedent inflammation, instrumentation, or operative history. Its histopathological diversity can create diagnostic dilemmas and pathologists utilize morphological evaluation along with available immunohistochemical markers to navigate these challenges. Immunohistochemical assays currently do not designate or specify nephrogenic adenoma's potential putative cell of origin. Leveraging single-cell RNA sequencing technology, we nominated a principal cell collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for nephrogenic adenoma. Immunohistochemical characterization revealed L1CAM to be positive in all 35 (100%) patient samples of nephrogenic adenoma; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma in situ, prostatic adenocarcinoma, majority of high-grade urothelial carcinoma, and metastatic urothelial carcinoma. In the study, we also utilized single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for proximal tubule, loop of Henle, and distal tubule (including principal and intercalated cells) which can be used to perform nephronal mapping utilizing RNA in situ hybridization and immunohistochemistry technology. Employing this technique on nephrogenic adenoma we found enrichment of both principal cell marker L1CAM and, the proximal tubule types-A and -B cells markers, PDZKI1P1 and PIGR respectively. The cell type markers for the intercalated cell of distal tubules (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in nephrogenic adenoma. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between distal tubule principal cell (P) cells and nephrogenic adenoma. L1CAM expression will be of potential value in assisting surgical pathologists towards a diagnosis of nephrogenic adenoma in challenging patient samples.
PubMed: 38901674
DOI: 10.1016/j.modpat.2024.100540 -
Oncotarget Jun 2024Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST... (Comparative Study)
Comparative Study
Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.
OBJECTIVES
Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction.
RESULTS
imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST < 0.0001 and = 0.015, respectively; mRECIST < 0.0001 and = 0.015, respectively).
METHODS
Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2-4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods.
CONCLUSION
For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).
Topics: Humans; Ipilimumab; Male; Nivolumab; Female; Aged; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Prognosis; Pleural Neoplasms; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Aged, 80 and over; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 38900646
DOI: 10.18632/oncotarget.28594 -
JAMA Otolaryngology-- Head & Neck... Jun 2024Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a...
IMPORTANCE
Whether F18-choline (FCH) positron emission tomographic (PET)/computed tomographic (CT) scan can replace Tc99m-sestaMIBI (MIBI) single-photon emission (SPE)CT/CT as a first-line imaging technique for preoperative localization of parathyroid adenomas (PTA) in patients with primary hyperparathyroidism (PHPT) is unclear.
OBJECTIVE
To compare first-line FCH PET/CT vs MIBI SPECT/CT for optimal care in patients with PHPT needing parathyroidectomy and to compare the proportions of patients in whom the first-line imaging method resulted in successful minimally invasive parathyroidectomy (MIP) and normalization of calcemia 1 month after surgery.
DESIGN, SETTING, AND PARTICIPANTS
A French multicenter randomized open diagnostic intervention phase 3 trial was conducted. Patients were enrolled from November 2019 to May 2022 and participated up to 6 months after surgery. The study included adults with PHPT and an indication for surgical treatment. Patients with previous parathyroid surgery or multiple endocrine neoplasia type 1 (MEN1) were ineligible.
INTERVENTIONS
Patients were assigned in a 1:1 ratio to receive first-line FCH PET/CT (FCH1) or MIBI SPECT/CT (MIBI1). In the event of negative or inconclusive first-line imaging, they received second-line FCH PET/CT (FCH2) after MIBI1 or MIBI SPECT/CT (MIBI2) after FCH1. All patients underwent surgery under general anesthesia within 12 weeks following the last imaging. Clinical and biologic (serum calcemia and parathyroid hormone levels) assessments were performed 1 and 6 months after surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome was a true-positive first-line imaging-guided MIP combined with uncorrected serum calcium levels of 2.55 mmol/l or less 1 month after surgery, corresponding to the local upper limit of normality.
RESULTS
Overall, 57 patients received FCH1 (n = 29) or MIBI1 (n = 28). The mean (SD) age of patients was 62.8 (12.5) years with 15 male (26%) and 42 female (74%) patients. Baseline patient characteristics were similar between groups. Normocalcemia at 1 month after positive first-line imaging-guided MIP was observed in 23 of 27 patients (85%) in the FCH1 group and 14 of 25 patients (56%) in the MIBI1 group. Sensitivity was 82% (95% CI, 62%-93%) and 63% (95% CI, 42%-80%) for FCH1 and MIBI1, respectively. Follow-up at 6 months with biochemical measures was available in 43 patients, confirming that all patients with normocalcemia at 1 month after surgery still had it at 6 months. No adverse events related to imaging and 4 adverse events related to surgery were reported.
CONCLUSIONS
This randomized clinical trial found that first-line FCH PET/CT is a suitable and safe replacement for MIBI SPECT/CT. FCH PET/CT leads more patients with PHPT to correct imaging-guided MIP and normocalcemia than MIBI SPECT/CT thanks to its superior sensitivity.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04040946.
PubMed: 38900416
DOI: 10.1001/jamaoto.2024.1421 -
Cancer Medicine Jun 2024To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical...
Discriminating atypical parotid carcinoma and pleomorphic adenoma utilizing extracellular volume fraction and arterial enhancement fraction derived from contrast-enhanced CT imaging: A multicenter study.
OBJECTIVES
To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation.
METHODS
From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application.
RESULTS
Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145).
CONCLUSIONS
ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.
Topics: Humans; Male; Female; Adenoma, Pleomorphic; Middle Aged; Parotid Neoplasms; Tomography, X-Ray Computed; Diagnosis, Differential; Aged; Adult; Contrast Media; ROC Curve; Retrospective Studies; Adenocarcinoma
PubMed: 38899534
DOI: 10.1002/cam4.7407 -
World Journal of Clinical Cases Jun 2024As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many...
BACKGROUND
As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes.
CASE SUMMARY
Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved.
CONCLUSION
Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.
PubMed: 38899290
DOI: 10.12998/wjcc.v12.i16.2813 -
Frontiers in Endocrinology 2024Post-operative CSF leak is the major source of morbidity following transsphenoidal approaches (TSA) and expanded endonasal approaches (EEA) to lesions of the sella...
AIMS
Post-operative CSF leak is the major source of morbidity following transsphenoidal approaches (TSA) and expanded endonasal approaches (EEA) to lesions of the sella turcica and the ventral skull base. There are conflicting reports in the literature as to whether obesity (BMI ≥30) is a risk factor for this complication. We aimed to evaluate data collected as part of prospective multi-centre cohort study to address this question.
METHODS
The CRANIAL (CSF Rhinorrhoea After Endonasal Intervention to the Skull Base) study database was reviewed and patients were divided into obese and non-obese cohorts. Data on patient demographics, underlying pathology, intra-operative findings and skull base repair techniques were analysed.
RESULTS
TSA were performed on 726 patients, of whom 210 were obese and 516 were non-obese. The rate of post-operative CSF leak in the obese cohort was 11/210 (5%), compared to 17/516 (3%) in the non-obese cohort, which was not statistically significant (χ 1.520, p=0.217). EEA were performed on 140 patients, of whom 28 were obese and 112 were non-obese. The rate of post-operative CSF leak in the obese cohort was 2/28 (7%), which was identical to the rate observed in the non-obese cohort 8/112 (7%) Fisher's Exact Test, p=1.000). These results persisted following adjustment for inter-institutional variation and baseline risk of post-operative CSF leak.
CONCLUSION
CSF leak rates following TSA and EEA, in association with modern skull base repair techniques, were found to be low in both obese and non-obese patients. However, due to the low rate of post-operative CSF leak, we were unable to fully exclude a small contributory effect of obesity to the risk of this complication.
Topics: Humans; Obesity; Female; Male; Skull Base; Cerebrospinal Fluid Leak; Middle Aged; Prospective Studies; Postoperative Complications; Adult; Aged; Endoscopy; Cerebrospinal Fluid Rhinorrhea; Risk Factors; Cohort Studies; Young Adult
PubMed: 38899009
DOI: 10.3389/fendo.2024.1353494 -
World Journal of Clinical Cases Jun 2024Salivary gland tumors are relatively rare. Most minor salivary gland tumors are malignant with benign tumors accounting for 18% of the tumors. Pleomorphic adenoma (PA)...
BACKGROUND
Salivary gland tumors are relatively rare. Most minor salivary gland tumors are malignant with benign tumors accounting for 18% of the tumors. Pleomorphic adenoma (PA) is the most common salivary gland tumor. Lip PA is uncommon with 9.8% occurring in the upper lip. We are adding on the knowledge of the rare upper lip PA (benign mixed tumor).
CASE SUMMARY
We report an upper lip PA (benign mixed tumor) in a 28-year-old man. His complaint was a painless swelling on the upper lip. A painless, non-tender, well-circumscribed, slightly mobile, sessile, nodular, and rubbery (in consistency) tumor measuring 5.0 cm x 2.0 cm was noted on the left side of his upper lip. The overlying skin was not fixed and of normal color. There was no ulceration, and palpation did not elicit pain or bleeding. There was no history of trauma. Blunt dissection was used to completely excise the nodular, whitish, and encapsulated tumor. Microscopy showed a well-circumscribed and partly encapsulated biphasic lesion, with large lobules of myxo-chondroid stroma and intervening cellular nodules of basaloid cells, well-formed tubules containing eosinic secretion, and nests of myoepithelial cells. A diagnosis of PA (benign mixed tumor) was confirmed.
CONCLUSION
Blunt dissection is indicated to preserve the cosmesis and function of the upper lip.
PubMed: 38898865
DOI: 10.12998/wjcc.v12.i17.3138 -
Ear, Nose, & Throat Journal Jun 2024To analyze the etiology, diagnosis, and treatment of unexplained conductive hearing loss (UCHL) with intact tympanic membrane. A systematic review was conducted based... (Review)
Review
To analyze the etiology, diagnosis, and treatment of unexplained conductive hearing loss (UCHL) with intact tympanic membrane. A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 642 articles were retrieved from databases such as PubMed, Embase, Web of Science, and Cochrane. Fifty-four research articles and 21 case reports were screened out according to the inclusion and exclusion criteria for analysis of the etiology of UCHL. Seven research articles with UCHL who underwent exploratory tympanotomy were selected for data extraction and analysis of clinical characteristics. UCHL is a common manifestation of various diseases, including congenital ossicular anomalies (COA), otosclerosis (OTS), congenital middle ear cholesteatoma (CMEC), oval window atresia, superior semicircular-canal dehiscence, congenital stapedial footplate fixation, middle ear osteoma or adenoma, congenital ossification of stapedial tendon, and so on. A total of 522 patients were included in the 7 articles; among whom OTS showed a tendency to increase with age. The main symptoms were hearing loss, followed by tinnitus, dizziness, ear fullness, ear pain, facial paralysis. A total of 87.5% to 93.0% patients with COA manifested as nonprogressive deafness that occurred since childhood, with tinnitus incidence of 15.6% to 30.2%, and 86.4% to 96.4% patients with OTS presented with progressive hearing loss, with tinnitus incidence of 60.1% to 90.9%. The diagnosis positive rate of high-resolution computed tomography (HRCT) was 33.8% to 87.1%, and CMEC was higher than that of COA (83.3%-100% vs 28.6%-64%). All the articles reported good hearing recovery. The most common surgical complications included taste abnormalities, tinnitus, and dizziness. UCHL presents with similar clinical manifestations and poses challenges in preoperative diagnosis. Exploratory tympanotomy is the primary method for diagnosis and treatment, with good prognosis after removing the lesion and reconstructing hearing during the operation. Children can also safely undergo the surgery.
PubMed: 38895947
DOI: 10.1177/01455613241262129 -
Journal of Clinical Medicine May 2024: Endoscopic papillectomy (EP) is the preferred treatment for ampullary tumors because it has fewer side effects than surgical removal. This study retrospectively...
: Endoscopic papillectomy (EP) is the preferred treatment for ampullary tumors because it has fewer side effects than surgical removal. This study retrospectively compared a new anchoring EP method (A-EP) with the conventional (C-EP) approach. : Ninety-nine patients who underwent EP at a single medical institution between 2009 and 2021 were retrospectively reviewed. In all patients, the indications for EP were pathological adenoma with <10 mm of biliary invasion and a tumor diameter <30 mm on endoscopic ultrasonography. The exclusion criteria were antiplatelet/anticoagulant use, previous upper GI surgery, or prior biliary/pancreatic endoscopic therapy. One expert endoscopist performed the two types of EPs, A-EP and C-EP. : Sixty-two patients underwent A-EP, and 37 underwent C-EP. There were no significant differences in baseline characteristics, such as sex, age, tumor size, and ductal invasion on endoscopic ultrasound. The A-EP group had higher en bloc resection rates (95.2% vs. 78.4%, = 0.010). Although the difference was not statistically significant, it tended towards fewer incidences of pancreatitis ( = 0.081) and duct stricture ( = 0.081). The recurrence rate was lower in the A-EP group (8.1% vs. 37.8%, = 0.000). There were no significant differences between the two groups regarding the follow-up period (A-EP vs. C-EP, 725 vs. 1045 days, = 0.109) or the days of recurrence (A-EP vs. C-EP, 341 vs. 562 days, = 0.551). : A-EP showed better outcomes than C-EP in terms of en bloc resection and recurrence rates, providing evidence for the efficacy of this novel EP method.
PubMed: 38892937
DOI: 10.3390/jcm13113226 -
Journal of Clinical Medicine May 2024The one-person technique (OPT) for colonoscope insertion is recommended by professional societies and regarded as standard practice. However, the two-person technique...
The one-person technique (OPT) for colonoscope insertion is recommended by professional societies and regarded as standard practice. However, the two-person technique (TPT) has shown several advantages over the OPT. The aim of this study was to evaluate the performance of the TPT compared to the OPT. In this prospective study, consecutive individuals presenting for outpatient colonoscopy were randomized to undergo colonoscopy by OPT or by TPT. The colonoscopies were performed by six endoscopists, two of whom were beginners, two with intermediate skills, and two who were experts. The primary endpoints were quality indicators for colonoscopy, including adenoma detection rate, cecal intubation rate, cecal insertion time, and total colonoscopy time. A secondary outcome was procedure tolerability, as assessed by both the patients and the endoscopists. Two hundred and four subjects (117 males, mean age 54.3) were randomized to either one- ( = 102) or two-person ( = 102) colonoscopy. The adenoma detection rate was 30.4% in OPT group and 34.3% in TPT group. ( = 0.55). No significant differences between the two groups were found in terms of cecal intubation rate (98/102 vs. 98/102), insertion time (411 vs. 381 s), and total examination time (1426 vs. 1296 s). However, patients receiving the TPT had lower pain scores than patients receiving the OPT. Endoscopist fatigue measured with the FACIT-F was also significantly lower in the TPT group. The two-person colonoscopy method was not shown to be technically or clinically inferior. Rather, the TPT can improve patient tolerance and reduce endoscopist fatigue.
PubMed: 38892851
DOI: 10.3390/jcm13113140