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OBJECTIVE: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). RESULTS: Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. CONCLUSIONS: Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement. TRIAL REGISTRATION NUMBER: NCT03656380.
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Transtornos de Deglutição , Esofagite Eosinofílica , Adulto , Humanos , Adolescente , Esofagite Eosinofílica/tratamento farmacológico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Resultado do Tratamento , Anticorpos Monoclonais Humanizados , Eosinófilos/patologia , Método Duplo-CegoRESUMO
This manuscript discusses a rare case of pediatric gastrointestinal mucormycosis in a hospitalized patient who presented in diabetic ketoacidosis. A review of the literature is summarized to provide an overview of mucormycosis with a discussion of the mechanisms underlying the susceptibility of diabetic patients for this condition.
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CONTEXT.: With the adoption of Epic/Beaker at our institution, surgical pathology specimens are assigned a Current Procedural Terminology (CPT) charge code at the time of accessioning, and pathologists have been made responsible for verifying the accuracy of the code before signing out the case. OBJECTIVE.: To determine with what frequency attending pathologists reassigned the correct charge code to a specimen when the code assigned at accessioning was incorrect, as well as to estimate the potential financial impact of missed changes. DESIGN.: We reviewed all specimens received for frozen section during a 7-month period, identified specimens where the default charge code that our departmental protocol assigns at frozen section (88305) was incorrect, and assessed the rate of successful code change by pathologists and the potential financial cost of each missed change. RESULTS.: Three hundred fifty-two of 2191 frozen section specimens (16%) required a change in the 88305 charge code. The codes for 195 specimens (55%) were correctly changed by the attending pathologist, while 157 (45%) were not changed (149) or were changed to an incorrect charge code (8). Individual pathologist change rates ranged from 0% to 100%, with a mean and median change rate of 43% and 24%, respectively. Using average code reimbursements at our institution, the loss in revenue from the 157 missed and incorrect frozen section changes was estimated at $13 788 ($1970 per month). CONCLUSIONS.: Pathologists showed highly variable rates of correcting CPT charge codes when the incorrect code had been previously assigned to a case, with associated loss of revenue from missed and incorrect code changes.
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Secções Congeladas , Patologia Cirúrgica , Humanos , Secções Congeladas/métodos , PatologistasRESUMO
Schistosomiasis is a parasitic trematode infection spread by snails with multiple species causing human disease. Infection can cause liver disease, including fibrosis and portal hypertension, and has been linked to malignancies such as bladder and colorectal cancer. We describe a case of Schistosoma mekongi, a geographically limited form of schistosomiasis, in a Laotian immigrant who presented with both hepatic fibrosis and rectal cancer, with numerous schistosome eggs present in the patient's rectal resection. We believe this case is the first report of a rectal carcinoma arising in the setting of S. mekongi infection.
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Immune responses vary in colorectal cancers, which strongly influence prognosis. However, little is known about the variance in immune response within preinvasive lesions. The study aims to investigate how the immune contexture differs by clinicopathologic features (location, histology, dysplasia) associated with progression and recurrence in early carcinogenesis. We performed a cross-sectional study using preinvasive lesions from the surgical pathology laboratory at the Medical University of South Carolina. We stained the tissues with immunofluorescence antibodies, then scanned and analyzed expression using automated image analysis software. We stained CD117 as a marker of mast cells, CD4/RORC to indicate Th17 cells, MICA/B as a marker of NK-cell ligands, and also used antibodies directed against cytokines IL6, IL17A, and IFNγ. We used negative binomial regression analysis to compare analyte density counts by location, histology, degree of dysplasia adjusted for age, sex, race, and batch. All immune markers studied (except IL17a) had significantly higher density counts in the proximal colon than distal colon and rectum. Increases in villous histology were associated with significant decreases in immune responses for IL6, IL17a, NK ligand, and mast cells. No differences were observed in lesions with low- and high-grade dysplasia, except in mast cells. The lesions of the proximal colon were rich in immune infiltrate, paralleling the responses observed in normal mucosa and invasive disease. The diminishing immune response with increasing villous histology suggests an immunologically suppressive tumor environment. Our findings highlight the heterogeneity of the immune responses in preinvasive lesions, which may have implications for prevention strategies. PREVENTION RELEVANCE: Our study is focused on immune infiltrate expression in preinvasive colorectal lesions; our results suggest important differences by clinicopathologic features that have implications for immune prevention research.
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Adenoma/patologia , Neoplasias Colorretais/patologia , Imunidade/fisiologia , Adenoma/diagnóstico , Adenoma/imunologia , Adenoma/metabolismo , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Colo/imunologia , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Estudos Transversais , Feminino , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: African Americans (AAs) have higher colorectal cancer (CRC) incidence and mortality rate than Caucasian Americans (CAs). Recent studies suggest that immune responses within CRCs contribute to the disparities. If racially distinct immune signatures are present in the early phases of carcinogenesis, they could be used to develop interventions to prevent or slow disease. METHODS: We selected a convenience sample of 95 patients (48 CAs, 47 AAs) with preinvasive colorectal adenomas from the surgical pathology laboratory at the Medical University of South Carolina. Using immunofluorescent-conjugated antibodies on tissue slides from the lesions, we quantified specific immune cell populations: mast cells (CD117+), Th17 cells (CD4+RORC+), and NK cell ligand (MICA/B) and inflammatory cytokines, including IL-6, IL-17A, and IFN-γ. We compared the mean density counts (MDCs) and density rate ratios (RR) and 95% CI of immune markers between AAs to CAs using negative binomial regression analysis. We adjusted our models for age, sex, clinicopathologic characteristics (histology, location, dysplasia), and batch. RESULTS: We observed no racial differences in age or sex at the baseline endoscopic exam. AAs compared to CAs had a higher prevalence of proximal adenomas (66% vs. 40%) and a lower prevalence of rectal adenomas (11% vs. 23%) (p =0.04) but no other differences in pathologic characteristics. In age, sex, and batch adjusted models, AAs vs. CAs had lower RRs for cells labeled with IFNγ (RR 0.50 (95% CI 0.32-0.81); p=0.004) and NK cell ligand (RR 0.67 (0.43-1.04); p=0.07). In models adjusted for age, sex, and clinicopathologic variables, AAs had reduced RRs relative to CAs for CD4 (p=0.02), NK cell ligands (p=0.01), Th17 (p=0.005), mast cells (p=0.04) and IFN-γ (p< 0.0001). CONCLUSIONS: Overall, the lower RRs in AAs vs. CAs suggests reduced effector response capacity and an immunosuppressive ('cold') tumor environment. Our results also highlight the importance of colonic location of adenoma in influencing these differences; the reduced immune responses in AAs relative to CAs may indicate impaired immune surveillance in early carcinogenesis. Future studies are needed to understand the role of risk factors (such as obesity) in influencing differences in immune responses by race.
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BACKGROUND AND AIMS: Updated diagnostic guidelines for eosinophilic esophagitis (EoE) have eliminated the requirement for a proton pump inhibitor (PPI) trial, but there are no models to identify patients with EoE based on these new criteria. We aimed to develop a predictive model for diagnosis of EoE based on the updated EoE diagnostic guidelines. METHODS: We performed a secondary analysis of a prospective study of adult patients referred for outpatient esophagogastroduodenoscopy at University of North Carolina who had symptoms of esophageal dysfunction; patients with prevalent EoE were excluded. We analyzed data from 206 EoE cases (mean age 40.1, 62.6% male, 93.2% white) and 306 controls (mean age 52.3, 37.9% male, 79.7% white). We built predictive models for case-control status, using clinical, endoscopic, and histologic features, and defining EoE by either the new or historical definition of PPI non-response. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC). RESULTS: Before endoscopy, younger age, male sex, history of atopic condition or food allergy, and dysphagia identified patients with EoE with an AUC of 0.83. When we included endoscopy findings suggestive of EoE, the model identified patients with EoE with an AUC of 0.92; this increased to 0.99 when histology was included. CONCLUSION: We developed a model to identify patients with EoE, without a trial of PPIs, based on updated diagnostic guidelines. Clinical features and endoscopic findings identified patients with EoE with an AUC of 0.92-even without histologic data and in the absence of dysphagia. This model can be used to select patients with upper gastrointestinal symptoms but without dysphagia for early diagnostic endoscopy. The model can also be used to identify cases of EoE when eosinophil counts are greater than 15 in biopsies but other causes of esophageal eosinophilia cannot necessarily be excluded.
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Esofagite Eosinofílica , Adulto , Endoscopia , Esofagite Eosinofílica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de PrótonsRESUMO
â¢Angiosarcoma is a rare endothelial malignancy associated with radiation exposure.â¢Very rarely, angiosarcoma has been reported to arise in the uterine cervix.â¢We report the first case of post-radiation angiosarcoma of the cervix.
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Anisakidosis is an acute and, less commonly, chronic gastrointestinal tract disease caused by the ingestion of nematode larvae contained within raw or undercooked seafood. We describe a case of chronic gastric anisakidosis diagnosed by endoscopic resection of submucosal nodules in a patient with a multi-year history of epigastric abdominal pain. This case illustrates the importance of maintaining a high index of suspicion for this diagnosis, even in patients with a remote history of seafood consumption or a chronic presentation of abdominal pain.
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PURPOSE: Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature. MATERIALS AND METHODS: Following IRB approval, CNB results from Duke University (7/1/2004-6/30/2014) and the University of North Carolina Chapel Hill (1/1/04-6/30/2013) were reviewed to identify non-atypical papillomas. All cases with surgical excision or 2â¯years of imaging follow up were included. In addition, a literature review identified 60 published studies on upgrades of NAPs diagnosed at CNB. Cases in our cohort and the published literature were reviewed for confounding factors: [1] missing radiologic-pathologic concordance and/or discordance, [2] papillomas included with high-risk lesions, [3] high risk lesions counted as upgrades, [4] review by a nonspecialized breast pathologist, and [5] cancer incidentally detected. RESULTS: Of the 388 CNBs in our dual-institution cohort, 136 (35%) patients underwent surgical excision and 252 (65%) patients had imaging follow up. After controlling for confounders, no cancers (0/388) were found at surgical excision or during follow up imaging. The literature review upstaging rate was 4.0% (166/4157) but 1.8% (4/227) after excluding studies with confounders. The combined upstaging rate from the literature and this study was 0.6% (4/615). CONCLUSION: The upstaging rate for CNB diagnosed NAPs was 0% in our cohort and 0.6% overall after adjusting for confounders. This low rate does not warrant reflexive surgical excision and diagnostic imaging follow up should be discretionary.
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Neoplasias da Mama/patologia , Mama/patologia , Papiloma/diagnóstico , Adulto , Idoso , Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores/métodos , Estadiamento de Neoplasias , Papiloma/diagnóstico por imagem , Papiloma/cirurgia , Radiologia/métodosRESUMO
Patients with Turner syndrome (TS) are known to be at risk for excess androgen production and virilization associated with gonadoblastoma and Y chromosome mosaicism, and excess androgens are a risk factor for the development of hepatocellular carcinoma. However, virilization and hepatocellular carcinoma have not been described in a patient with TS. A 10-year-old with nonmosaic 45,X TS presented with clitoromegaly, accelerated linear growth velocity, advanced bone age, and elevated testosterone levels as well as a second occurrence of hepatocellular carcinoma. Gonadectomy was performed, and pathology revealed hilus cell hyperplasia. Immunohistochemical staining of both the original and recurrent hepatocellular carcinoma tissues was diffusely positive for androgen receptors. After gonadectomy, testosterone levels were measurable but normal, with no further virilization; however, the liver mass continued to grow. Ovarian hilus cell hyperplasia should be considered a potential etiology for virilization in the TS population. Excess endogenous testosterone exposure in girls and women with TS may be associated with hepatocellular carcinoma expressing the androgen receptor, though normalizing testosterone levels may not lead to tumor regression in these cases.
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PURPOSE OF REVIEW: The purpose of this review is to summarize the management of serrated colorectal polyps (SPs), with a particular focus on the most common premalignant SP, sessile serrated adenoma or polyp (SSA/P). These lesions present a challenge for endoscopists with respect to detection and resection, and are also susceptible to pathologic misdiagnosis. RECENT FINDINGS: Patients with SSA/Ps are at an increased risk of future colorectal neoplasia, including advanced polyps and cancer. Reasonable benchmarks for SP detection rates are 5-7% for SSA/Ps and 10-12% for proximal SPs. Certain endoscopic techniques such as chromoendoscopy, narrow band imaging, water immersion, and wide-angle viewing may improve SSA/P detection. Emerging endoscopic techniques such as underwater polypectomy, suction pseudopolyp technique, and piecemeal cold snare polypectomy are helpful tools for the endoscopist's armamentarium for removing SSA/Ps. Proper orientation of SSA/P specimens can improve the accuracy of pathology readings. Patients with confirmed SSA/Ps and proximal HPs should undergo surveillance at intervals similar to what is recommended for patients with conventional adenomas. Patients with SSA/Ps may also be able to lower their risk of future polyps by targeting modifiable risk factors including tobacco and alcohol use and high-fat diets. NSAIDs and aspirin appear to be protective agents. SPs and SSA/Ps in particular are important colorectal cancer precursors that merit special attention to ensure adequate detection, resection, and surveillance.
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Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive malignancy of the central nervous system (CNS) usually diagnosed in infancy or childhood, most often characterized by loss of expression of the SMARCB1 gene product integrase interactor 1 (INI1) protein. We report a case of AT/RT in a 3 month old boy with retained expression of INI1 by immunohistochemistry. Additional testing demonstrated loss of expression of the SMARCA4 gene product Brahma-related gene 1 (BRG1) protein by immunohistochemistry, confirmed by next generation sequencing showing a nonsense mutation in SMARCA4. This case illustrates that positivity for INI1 does not rule out a diagnosis of AT/RT, and additional testing, including BRG1/SMARCA4 analysis, is warranted in cases where clinical suspicion is high.
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DNA Helicases/genética , Proteínas Nucleares/genética , Tumor Rabdoide/genética , Proteína SMARCB1/genética , Teratoma/genética , Fatores de Transcrição/genética , Códon sem Sentido , Humanos , Lactente , Masculino , Tumor Rabdoide/patologia , Teratoma/patologiaRESUMO
Ill or immunosuppressed hospital patients are at increased risk for herpes simplex and herpes zoster virus infections, with high potential morbidity and mortality. Here, we present two cases of reactivation of herpes virus infections with delay in diagnosis, with ultimately fatal results. Since these infections are treatable, it is important to keep a high index of suspicion to facilitate early diagnosis and treatment.
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Immunoglobulin G4-related lymphadenopathy (IgG4-RLAD) occurs in the setting of extranodal IgG4-related disease (IgG4-RD), an immune-mediated process described in many organ systems characterized by lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells and fibrosis. Although the morphologic features in the lymph node sometimes resemble those seen at the extranodal sites, 5 microscopic patterns have been described, most of which resemble reactive lymphoid hyperplasia. This morphologic variability leads to unique diagnostic challenges and a broad differential diagnosis. As IgG4-RD may be exquisitely responsive to steroids or other immunotherapy, histologic recognition and inclusion of IgG4-RLAD in the differential diagnosis is vital.
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Doenças Autoimunes/diagnóstico , Imunoglobulina G/sangue , Linfadenopatia/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Biópsia , Diagnóstico Diferencial , Humanos , Linfonodos/patologia , Linfadenopatia/imunologia , Linfadenopatia/patologia , Linfoma/diagnóstico , Plasmócitos/imunologia , Plasmócitos/patologia , PrognósticoRESUMO
INTRODUCTION: Rapid on-site evaluation (ROSE) increases adequacy and diagnostic yield of cytology procedures and provides information for rapid clinical decisions. Cytology procedures with ROSE (fine-needle aspiration [FNA] and touch preparation with core biopsy [TP + CB]) are used to evaluate renal lesions, especially prior to concomitant ablation. MATERIALS AND METHODS: Consecutive image-guided procedures of FNA and TP + CB of renal lesions with ROSE were reviewed for a ten year period. ROSE diagnoses were correlated with final diagnoses and clinical course. Diagnoses were considered in five categories: positive, atypical/suspicious, nonspecific (including adequate, lesional, cellular, and oncocytic descriptors), negative, and nondiagnostic. Statistical analysis was performed using Fisher's exact test. RESULTS: A total of 209 procedures with 226 ROSE (73 FNA, 119 TP + CB, 17 FNA + TP + CB) were performed. FNAs had more nondiagnostic specimens than CBs by both ROSE and final diagnosis (19 of 90 versus 7 of 136 for ROSE [P = 0.0004], 15 of 90 versus 5 of 136 for final [P = 0.0013]). More FNAs than CBs were positive by ROSE (33 of 90 versus 23 of 136, P = 0.0009), with no difference in positive final diagnoses (66 of 90 versus 106 of 136, P = 0.43). Treatment following diagnosis included ablation (67, with 42 concomitant after ROSE), surgical resection (50), chemotherapy/radiation (42), re-biopsy (5), serial imaging (15), no treatment/other (15), and lost to follow up (15). CONCLUSIONS: All lesions with positive ROSE had positive final diagnoses. For cases with positive final diagnoses, ROSE diagnoses were relatively evenly distributed among positive, atypical/suspicious, and nonspecific. TP + CB had higher adequacy than FNA by both ROSE and final diagnosis, although FNAs more often had positive ROSE diagnoses.
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We report the neuroimaging and histopathologic findings of a 12-year-old female patient with a disseminated oligodendroglial-like leptomeningeal tumor with anaplastic progression and presumed extraneural metastatic disease. These tumors may represent distinct pathology primarily seen in pediatric patients. Neuroimaging demonstrates diffuse, progressive enhancement of the leptomeninges often with interval development of intraparenchymal lesions on follow-up. Disease is typically confined to the central nervous system, though diffuse peritoneal disease was seen in our case, possibly through metastatic seeding of the abdomen via ventriculoperitoneal shunt.