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1.
Mod Pathol ; : 100543, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897453

RESUMO

Gastrointestinal (GI) tract involvement by Langerhans cell histiocytosis (LCH) is rare and its clinicopathologic characteristics have only been described in case reports and small series. We reviewed hematoxylin and eosin- and CD1a, S100, and Langerin immunohistochemical-stained slides from 47 patients with well-documented demographic and clinical findings. Our cases included 8 children and 39 adults, with a mean follow-up of 63 months. All pediatric patients had concurrent multisystem LCH, presented with GI symptoms, and showed non-polypoid lesions. Seven (88%) showed multifocal GI disease, including five with multiple GI organ involvement. All sampled lesions from children exhibited infiltrative growth. More than half had died of the disease or manifested persistent LCH at last follow-up. Twenty-five of 39 (64%) adults had LCH involving only the GI tract (single-system), with the remaining 14 (36%) exhibiting multi-system disease. Adult single-system GI LCH was typically encountered incidentally on screening/surveillance endoscopy (72%). Most exhibited isolated colorectal involvement (88%) as a solitary polyp (92%), with a well-demarcated/noninfiltrative growth pattern (70%), and excellent prognosis (100%). In comparison, adult patients with multi-system LCH more frequently presented with GI symptoms (92%, P<0.001), non-colorectal GI site involvement (50%, P=0.02), multifocal GI lesions (43%, P=0.005), non-polypoid lesions (71%, P<0.001), infiltrative histologic growth pattern (78%, P=0.04), and persistent disease (57%, P<0.001). Adult multi-system LCH patients appear to exhibit similar clinicopathologic features to those of pediatric patients. These results demonstrate that adults with single-system LCH involving the GI tract have an excellent prognosis, while multi-system LCH occurring at any age carries an unfavorable prognosis. High-risk features of GI LCH include pediatric age, GI symptomatology, non-colorectal GI involvement, multifocal GI disease, non-polypoid lesions, and infiltrative growth pattern.

2.
Ann Surg ; 273(6): e206-e213, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31290765

RESUMO

OBJECTIVE: The aim of the study was to investigate whether inhibition of Sonic Hedgehog (SHH) pathway would prevent progression of Barrett's Esophagus (BE) to esophageal adenocarcinoma. BACKGROUND: The hedgehog signaling pathway is a leading candidate as a molecular mediator of BE and esophageal adenocarcinoma (EAC). Repurposed use of existing off-patent, safe and tolerable drugs that can inhibit hedgehog, such as itraconazole, could prevent progression of BE to EAC. METHODS: The efficacy of itraconazole was investigated using a surgical rat reflux model of Barrett's Metaplasia (BM). Weekly intraperitoneal injections of saline (control group) or itraconazole (treatment group; 200 mg/kg) were started at 24 weeks postsurgery. Esophageal tissue was harvested at 40 weeks. The role of the Hh pathway was also evaluated clinically. Esophageal tissue was harvested after 40 weeks for pathological examination and evaluation of the SHH pathway by immunohistochemistry. RESULTS: BM was present in control animals 29 of 31 (93%) versus itraconazole 22 of 24 (91%). EAC was significantly lower in itraconazole 2 of 24 (8%) versus control 10 of 31 (32%), respectively (P = 0.033). Esophageal SHH levels were lower in itraconazole vs control (P = 0.12). In esophageal tissue from humans with recurrent or persistent dysplastic BE within 24 months of ablative treatment, strong SHH and Indian Hedgehog expression occurred in distal BE versus proximal squamous epithelium, odds ratio = 6.1 (95% confidence interval: 1.6, 23.4) and odds ratio = 6.4 (95% confidence interval: 1.2, 32.8), respectively. CONCLUSION: Itraconazole significantly decreases EAC development and SHH expression in a preclinical animal model of BM. In humans, BE tissue expresses higher SHH, Indian Hedgehog, and bone morphogenic protein levels than normal squamous esophageal epithelium.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etiologia , Esôfago de Barrett/complicações , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/etiologia , Proteínas Hedgehog/antagonistas & inibidores , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Adenocarcinoma/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Neoplasias Esofágicas/patologia , Masculino , Invasividade Neoplásica , Ratos , Ratos Sprague-Dawley
3.
Biochem Biophys Res Commun ; 508(2): 380-386, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30502090

RESUMO

Little is known about an oncogenic signal transducer ß-1,4-galactosyltransferase-V (ß-1,4-GalT-V), in human colorectal cancer. Using quantitative RT-PCR, immunohistochemical staining and ELISA assays, we determined that ß-1,4-GalT-V gene/protein expression is specifically increased in human colorectal cancer (CRC) tumors, compared to visibly normal tissue. Furthermore, we observed a marked increase in its enzymatic activity, and its product lactosylceramide. Moreover, we found increased dihydrosphingolipid metabolites, in particular dihydrosphingomyelin in cancer tissue compared to normal. Further, inhibition of glycosphingolipid synthesis by the synthetic ceramide analog, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), concurrently inhibited colorectal cancer cell (HCT-116) proliferation, as well as ß-1,4-GalT-V mass and several glycosphingolipid levels. We conclude that ß-1,4-GalT-V may serve as a diagnostic and therapeutic biomarker for the progression of human colorectal cancer, and consequently, inhibition of GSL synthesis may be a novel approach for the treatment of this life-threatening disease.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/enzimologia , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Biomarcadores Tumorais/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Galactosiltransferases/antagonistas & inibidores , Células HCT116 , Humanos , Imuno-Histoquímica , Lactosilceramidas/biossíntese , Morfolinas/administração & dosagem , Morfolinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Esfingolipídeos/biossíntese , Regulação para Cima
4.
Pancreatology ; 17(3): 490-496, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28416122

RESUMO

BACKGROUND/OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date. METHODS: We compared 142 MCNs and 746 IPMNs resected at a single institution. MCNs were reviewed for confirmation of ovarian-type stroma and reclassified according to current WHO guidelines. RESULTS: MCNs presented almost exclusively in middle-aged women (median 47.5 years, 96.5% female) as solitary (100%), macrocystic (94.2%) lesions in the distal pancreas (92.1%). IPMNs were distributed equally by sex in an older population (median 69.0 years, 49.6% female) and favored the proximal pancreas (67.6%). Compared with IPMNs, MCNs were larger (4.2 cm vs 2.5 cm) and more often low-grade (71.1% vs 13.8%). Associated invasive carcinoma was less common in MCNs than in IPMNs (9.9% vs 32.4%). Surgical resection was curative for 100% of noninvasive MCNs. Patients with an MCN-associated invasive carcinoma had a much better prognosis than did patients with an IPMN-associated invasive carcinoma with 10-year disease-specific survival of 79.6% versus 27.2%, respectively. CONCLUSION: MCNs have a stereotypical clinical profile that is readily distinguishable from IPMNs based on demographic features, imaging, and pathology. Most MCNs are noninvasive and curable with surgical resection. Prognosis remains excellent even for invasive disease with 10-year survival approaching 80% following resection.


Assuntos
Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Pancreáticas/cirurgia , Papiloma Intraductal/cirurgia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/diagnóstico por imagem , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Papiloma Intraductal/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Análise de Sobrevida , Resultado do Tratamento
7.
Diagn Cytopathol ; 51(2): E75-E81, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36354028

RESUMO

B3 thymoma is a rare malignant type of thymic epithelial neoplasm found in the anterior mediastinum. Diagnosis of thymoma from fine needle aspiration (FNA) can be challenging due to the infrequency of sampling and its morphologic overlap with other entities such as squamous cell carcinoma, lymphoma or thyroid carcinoma. We report a case of B3 thymoma mimicking poorly differentiated thyroid carcinoma. We present its diagnostic pitfalls on cytology specimens, especially where it concerns identifying the correct location of the lesion, discuss the differential diagnosis, and correlation with the corresponding surgical resection specimen. A neck computed tomography angiogram (CTA) revealed a partially calcified 2.1 cm mass inferior to the left thyroid lobe in a 51 yr old woman being evaluated for stroke/TIA symptoms. She was referred for evaluation of the lesion. On the initial FNA and core needle biopsy, the lesion showed high-grade epithelioid cells with abundant lymphocytic infiltration and occasional necrosis, and was diagnosed as a high-grade carcinoma, favored to represent a poorly differentiated thyroid carcinoma considering the location on imaging. The patient subsequently underwent total thyroidectomy, central neck dissection, and thymectomy. Final surgical pathologic diagnosis indicated a type B3 thymoma. Due to the infrequency of sampling, thymoma poses a diagnostic challenge on preoperative FNA or core needle biopsy. Herein, we present a case of B3 thymoma with a preoperative cytologic specimen that consisted of hyperchromatic sheets of epithelioid tumor cells with a background of lymphocytes without definitive follicular cells or colloid. The core needle biopsy and cell block material showed abundant necrosis, intermixed lymphocytes and neoplastic epithelial cells with strong positive staining for pan-keratin and p40. The cytology and core needle biopsy material were interpreted as representing a probable thyroid neoplasm and raised a broad differential including anaplastic thyroid carcinoma, poorly differentiated thyroid carcinoma with squamous features, metastatic squamous carcinoma, and metastatic carcinoma to a lymph node. The final surgical resection specimen showed a B3 type-thymoma.


Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Timoma , Neoplasias do Timo , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Feminino , Humanos , Timoma/diagnóstico , Timoma/patologia , Biópsia por Agulha Fina , Neoplasias do Timo/diagnóstico , Neoplasias do Timo/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Necrose
8.
Am J Clin Pathol ; 160(4): 411-416, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37289424

RESUMO

OBJECTIVES: Lobular capillary hemangioma (LCH) rarely involves the gastrointestinal (GI) tract. This study describes clinicopathologic features of LCH in a cohort of GI cases. METHODS: We defined lobular capillary hemangioma as "a proliferation of capillary-sized blood vessels arranged at least focally in a lobular configuration," searched departmental archives for cases, and recorded clinicopathologic findings. RESULTS: We identified 34 GI tract LCHs from 16 men and 10 women; 4 patients had multiple lesions. Mean age was 64 years. Cases arose in the esophagus (n = 7), stomach (n = 3), small bowel (n = 7), and colorectum (n = 17). Twelve patients had anemia or rectal bleeding. No patients had a known genetic syndrome. The lesions manifested as mucosal polyps, with median size of 1.3 cm. Microscopically, 20 lesions were ulcerated, and most involved the mucosa, with 9 extending into the submucosa. Vessel dilation was present in 27 patients, endothelial hobnailing in 13, hemorrhage in 13, and focal reactive stromal atypia in 2. Follow-up information was available for 10 patients, none of whom developed same-site recurrence. Six of the 26 cases (23%) were extradepartmental consultations, including 2 of the multifocal cases. CONCLUSIONS: Gastrointestinal tract LCHs often arise as colorectal polyps. They are typically small but can reach a few centimeters in size and can be multifocal.


Assuntos
Granuloma Piogênico , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Granuloma Piogênico/patologia , Trato Gastrointestinal/patologia , Mucosa/patologia , Esôfago/patologia
10.
Hum Pathol ; 126: 19-27, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35489437

RESUMO

Programmed death ligand 1 (PD-L1) dysregulation has been implicated in chronic inflammatory diseases, but its role in regulating intestinal mucosa inflammation is still unclear. The aim of this study was to assess PD-L1 expression in the intestinal mucosa of patients with refractory inflammatory bowel disease (IBD) compared to controls. We evaluated PD-L1 expression by immunohistochemistry in colectomy specimens of patients with ulcerative colitis (UC) and Crohn disease (CD) compared to controls. PD-L1 expression was assessed in colonic epithelium and inflammatory cells, along with the location of the inflammatory cells expressing PD-L1. All cases were stained with CD3, CD4, CD8, FOXP3, CD20, CD68, and CD90 immunostains to determine the types of cells expressing PD-L1. The UC group showed significantly higher PD-L1 expression in the colonic epithelium than both CD and control groups (both P < 0.001), and CD was also significantly higher than the control group (P = 0.004). Both UC and CD groups showed similar PD-L1 expression in the inflammatory infiltrate but significantly higher than the control group (both P < 0.001). Among both IBD groups, higher IBD activity was associated with higher levels of PD-L1 expression in the colonic epithelium (P < 0.05) and inflammatory infiltrate (P < 0.001). When comparing PD-L1 expression to lineage-specific markers, CD3+, CD4+ T cells, CD68+ macrophages, and CD90+ colonic stromal cells appeared to be expressing PD-L1. These findings implicate a role for PD-L1 in the dysregulation of the immune response in refractory IBD. Further studies are warranted to better understand the role of the immune regulatory pathways in intestinal mucosa.


Assuntos
Antígeno B7-H1/genética , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Antígeno B7-H1/metabolismo , Colite Ulcerativa/genética , Doença de Crohn/genética , Humanos , Mucosa Intestinal
11.
Am J Surg Pathol ; 46(4): 567-575, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864775

RESUMO

The rate of syphilis in the United States has been increasing steadily in the past decade, but it remains an uncommon diagnosis in tissue biopsies. Most of the pathology literature on hepatic syphilis consists of older series or case reports. This study aimed to systematically characterize the histologic spectrum of hepatic syphilis in a contemporary cohort. Clinicopathologic features of 14 hepatic syphilis cases between 2012 and 2018 were analyzed to characterize the broad spectrum of histologic changes. Thirteen patients were men (age range: 19 to 59 y); 6 had known human immunodeficiency virus, 7 were men known to have sex with men, and no patient had known prior syphilis. Hepatic syphilis was the primary clinical suspicion in only 1 patient. Common symptoms included jaundice, rash, and abdominal pain. Thirteen had elevated transaminases, and 12 had elevated alkaline phosphatase. Pathologic changes were grouped into 5 histologic patterns: biliary-pattern injury (n=5), acute hepatitis (n=4), autoimmune hepatitis-like (n=1), fibroinflammatory mass-forming lesion (n=2), and no particular pattern (n=2). Nearly all showed portal and lobular lymphocytes and plasma cells; 12 had prominent histiocytes/Kupffer cells, 9 had ductular reaction, and 7 had duct inflammation. Occasional focal findings included dropout (n=7), phlebitis (n=7), and loose granulomata (n=5). Treponeme immunohistochemistry was positive in 10 and negative in 4, though treatment was given before biopsy in 3 of those 4. Thirteen patients had rapid plasma reagin testing either before or after biopsy, with 1:64 or higher titer. All patients who received treatment recovered. Hepatic syphilis is rare but likely underrecognized. It exhibits a variety of histologic appearances and therefore should be considered in several hepatic differential diagnoses, especially in men who have sex with men. Kupffer cells, granulomata, and phlebitis may suggest the diagnosis regardless of predominant histologic pattern. Negative treponeme immunohistochemical staining does not exclude the diagnosis, including in untreated patients.


Assuntos
Hepatite , Flebite , Minorias Sexuais e de Gênero , Sífilis , Adulto , Feminino , Homossexualidade Masculina , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Flebite/complicações , Sífilis/diagnóstico , Sífilis/patologia , Adulto Jovem
12.
Int J Surg Pathol ; 29(5): 529-533, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33289418

RESUMO

Hereditary pancreatitis is a rare form of recurrent acute pancreatitis that typically has an onset in early adulthood. We report a rare case of hereditary pancreatitis in an individual with a serine protease inhibitor Kazal type 1 (SPINK1) mutation. Histologically the pancreas showed features of chronic pancreatitis with variable fibrosis, acinar destruction, and prominent inspissated secretions within the pancreatic ducts. Additionally, focal areas of low-grade pancreatic intraepithelial neoplasia (PanIN) were present. Although the histopathology of common gene mutations resulting in hereditary pancreatitis have been well described, the histopathology of pancreatitis secondary to SPINK1 mutation has been described in only one previous study.


Assuntos
Pâncreas/patologia , Pancreatite Crônica/diagnóstico , Inibidor da Tripsina Pancreática de Kazal/genética , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Transplante das Ilhotas Pancreáticas , Mutação , Pâncreas/cirurgia , Pancreatectomia , Pancreatite Crônica/genética , Pancreatite Crônica/patologia , Pancreatite Crônica/terapia , Recidiva , Exacerbação dos Sintomas , Adulto Jovem
13.
Am J Clin Pathol ; 155(6): 802-814, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33914058

RESUMO

OBJECTIVES: The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae. METHODS: We aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group. RESULTS: We were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P < .05) and mild focal lobular activity (6/8, 75%, P = .06). CONCLUSIONS: We found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases.


Assuntos
COVID-19/virologia , Formaldeído , Fígado/patologia , SARS-CoV-2/patogenicidade , Fixação de Tecidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inflamação/patologia , Fígado/virologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Fixação de Tecidos/métodos
14.
Am J Surg Pathol ; 44(9): 1251-1258, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32301754

RESUMO

Malakoplakia is an inflammatory process related to defective macrophage response to bacterial infection. To further characterize the clinicopathologic manifestations of gastrointestinal malakoplakia, 26 cases were identified from 6 institutions. Hematoxylin and eosin-stained slides and available stains were reviewed, and pertinent clinicopathologic features analyzed. Sixteen patients were women (62%). Mean patient age was 64 (range: 24 to 83). Sites included the colorectum (n=23), appendix (n=1), and stomach (n=2). Clinical indications for tissue procurement included screening (n=14), tumor resection (n=5), diarrhea (n=1), adenoma surveillance (n=1), ulcerative colitis flare (n=1), abdominal pain (n=1), and appendicitis (1). All cases featured histiocytes with abundant, pale, eosinophilic cytoplasm focally containing Michaelis-Gutmann bodies. The process frequently involved the mucosa (n=19), with architectural distortion in 13 cases. Lymphoid aggregates were present in 18 cases, which were prominent or obscuring in 11 (all colon biopsies) and provoked concern for lymphoma in 2. Associated findings included adenocarcinoma (n=5), adenoma (n=2), gastric hyperplastic polyps (n=1), chemical gastritis (n=1), collagenous colitis (n=1), and active chronic colitis (n=2). In cases with available stains, Michaelis-Gutman bodies were highlighted by Periodic Acid-Schiff with diastase, Von Kossa, and iron stains. Although 2 cases were positive for Tropheryma whipplei antibody, no T. whipplei transcripts were detected on real-time polymerase chain reaction. All patients with available follow-up are alive and well with no additional instances of malakoplakia. Malakoplakia of the gastrointestinal tract is a benign, incidental finding. Although histologic features in the stomach and colon resections are similar to those at other sites, exuberant lymphocytic response in colon biopsies and immunoreactivity with T. whippleii antibody may provoke initial confusion and lead to unnecessary time and resource investment.


Assuntos
Gastroenteropatias/patologia , Trato Gastrointestinal/patologia , Achados Incidentais , Malacoplasia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Mucosa Gástrica/patologia , Gastroenteropatias/microbiologia , Trato Gastrointestinal/microbiologia , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Tropheryma/genética , Estados Unidos , Adulto Jovem
15.
Am J Surg Pathol ; 44(6): 793-798, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31934919

RESUMO

Colon polypectomy can require an injection of a submucosal lifting agent to fully visualize and completely remove the polyp. To the best of our knowledge, this is the largest morphologic series on the novel lifting agents Eleview and Orise. The study consisted of 1 polypectomy and 8 colon resections from 9 patients: 6 women, 3 men (mean age=64 y); Orise=6, Eleview=3; the median time interval between injection and resection=16 weeks. Pathologic diagnoses of the polyps included tubular adenoma (n=4), tubulovillous adenoma (n=4), and sessile serrated adenoma/polyp (n=1). We report that a histologically processed Orise aliquot from the manufacturer showed similar histology to that seen in the specimens from patients with confirmed Orise injection. The morphology of the agents in the patient specimens changed with time status postinjection: immediate resection of the lifting agent showed basophilic, amorphous, and bubbly-extracellular material with prominent hemorrhage, and resection ∼3 months after lifting agent injection showed prominent hyalinized, pink-amorphous ribbons and globules with a foreign body giant cell reaction and fibrosis. The epicenter of the lifting agents was in the submucosa, and the agents were neither refractile nor polarizable. Because of the morphologic overlap with amyloid, 5 cases were stained with Congo Red, and all cases were negative. In conclusion, awareness of the morphology of these new lifting agents is important for accurate diagnosis and to avoid the diagnostic pitfall of amyloid. These lesions can be definitively distinguished from amyloid by their nonreactivity on a Congo Red and familiarity with their characteristic clinicopathologic presentation.


Assuntos
Amiloidose/patologia , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Poloxâmero , Amiloidose/diagnóstico , Pólipos do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poloxâmero/efeitos adversos
16.
Sci Adv ; 6(35): eabb1093, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32923633

RESUMO

Implantable drug release platforms that offer wirelessly programmable control over pharmacokinetics have potential in advanced treatment protocols for hormone imbalances, malignant cancers, diabetic conditions, and others. We present a system with this type of functionality in which the constituent materials undergo complete bioresorption to eliminate device load from the patient after completing the final stage of the release process. Here, bioresorbable polyanhydride reservoirs store drugs in defined reservoirs without leakage until wirelessly triggered valve structures open to allow release. These valves operate through an electrochemical mechanism of geometrically accelerated corrosion induced by passage of electrical current from a wireless, bioresorbable power-harvesting unit. Evaluations in cell cultures demonstrate the efficacy of this technology for the treatment of cancerous tissues by release of the drug doxorubicin. Complete in vivo studies of platforms with multiple, independently controlled release events in live-animal models illustrate capabilities for control of blood glucose levels by timed delivery of insulin.

17.
Am J Surg Pathol ; 43(5): 688-694, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30720534

RESUMO

Selective internal radiation therapy with Y-TheraSphere or Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 µm in diameter, and an occasional internal bulls'-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and Y-TheraSpheres. In conclusion, recognition of Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with Y-SIRSphere, but can be differentiated based on Y-TheraSpheres' colorless appearance with occasional internal bulls'-eyes with the condenser out and an internal cross with polarized light.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Microscopia de Polarização , Microesferas , Pessoa de Meia-Idade , Tamanho da Partícula , Compostos Radiofarmacêuticos/efeitos adversos , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
18.
Sci Adv ; 5(7): eaaw1899, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31281889

RESUMO

Continuous measurements of pressure and temperature within the intracranial, intraocular, and intravascular spaces provide essential diagnostic information for the treatment of traumatic brain injury, glaucoma, and cardiovascular diseases, respectively. Optical sensors are attractive because of their inherent compatibility with magnetic resonance imaging (MRI). Existing implantable optical components use permanent, nonresorbable materials that must be surgically extracted after use. Bioresorbable alternatives, introduced here, bypass this requirement, thereby eliminating the costs and risks of surgeries. Here, millimeter-scale bioresorbable Fabry-Perot interferometers and two dimensional photonic crystal structures enable precise, continuous measurements of pressure and temperature. Combined mechanical and optical simulations reveal the fundamental sensing mechanisms. In vitro studies and histopathological evaluations quantify the measurement accuracies, operational lifetimes, and biocompatibility of these systems. In vivo demonstrations establish clinically relevant performance attributes. The materials, device designs, and fabrication approaches outlined here establish broad foundational capabilities for diverse classes of bioresorbable optical sensors.


Assuntos
Implantes Absorvíveis , Técnicas Biossensoriais , Pressão Intracraniana/fisiologia , Monitorização Fisiológica , Humanos , Interferometria/métodos , Imageamento por Ressonância Magnética/métodos , Dispositivos Ópticos , Fótons , Silício/química , Temperatura
19.
Nat Biomed Eng ; 3(8): 644-654, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31391594

RESUMO

Capabilities in real-time monitoring of internal physiological processes could inform pharmacological drug-delivery schedules, surgical intervention procedures and the management of recovery and rehabilitation. Current methods rely on external imaging techniques or implantable sensors, without the ability to provide continuous information over clinically relevant timescales, and/or with requirements in surgical procedures with associated costs and risks. Here, we describe injectable classes of photonic devices, made entirely of materials that naturally resorb and undergo clearance from the body after a controlled operational lifetime, for the spectroscopic characterization of targeted tissues and biofluids. As an example application, we show that the devices can be used for the continuous monitoring of cerebral temperature, oxygenation and neural activity in freely moving mice. These types of devices should prove useful in fundamental studies of disease pathology, in neuroscience research, in surgical procedures and in monitoring of recovery from injury or illness.


Assuntos
Implantes Absorvíveis , Técnicas Biossensoriais/instrumentação , Óptica e Fotônica/instrumentação , Análise Espectral/métodos , Animais , Materiais Biocompatíveis , Engenharia Biomédica/instrumentação , Análise Química do Sangue/instrumentação , Análise Química do Sangue/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Desenho de Equipamento , Feminino , Camundongos , Modelos Animais , Neurociências , Fibras Ópticas , Silício/química , Temperatura
20.
Nat Biomed Eng ; 3(1): 37-46, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932064

RESUMO

Pressures in the intracranial, intraocular and intravascular spaces are clinically useful for the diagnosis and management of traumatic brain injury, glaucoma and hypertension, respectively. Conventional devices for measuring these pressures require surgical extraction after a relevant operational time frame. Bioresorbable sensors, by contrast, eliminate this requirement, thereby minimizing the risk of infection, decreasing the costs of care and reducing distress and pain for the patient. However, the operational lifetimes of bioresorbable pressure sensors available at present fall short of many clinical needs. Here, we present materials, device structures and fabrication procedures for bioresorbable pressure sensors with lifetimes exceeding those of previous reports by at least tenfold. We demonstrate measurement accuracies that compare favourably to those of the most sophisticated clinical standards for non-resorbable devices by monitoring intracranial pressures in rats for 25 days. Assessments of the biodistribution of the constituent materials, complete blood counts, blood chemistry and magnetic resonance imaging compatibility confirm the biodegradability and clinical utility of the device. Our findings establish routes for the design and fabrication of bioresorbable pressure monitors that meet requirements for clinical use.


Assuntos
Implantes Absorvíveis , Doença Crônica , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Dióxido de Silício/química , Temperatura , Cicatrização , Animais , Feminino , Cinética , Imageamento por Ressonância Magnética , Masculino , Camundongos , Ratos Endogâmicos Lew , Distribuição Tecidual
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