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1.
Cell Rep Med ; 5(3): 101447, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38442713

RESUMO

There is an unmet clinical need for a non-invasive and cost-effective test for oral squamous cell carcinoma (OSCC) that informs clinicians when a biopsy is warranted. Human beta-defensin 3 (hBD-3), an epithelial cell-derived anti-microbial peptide, is pro-tumorigenic and overexpressed in early-stage OSCC compared to hBD-2. We validate this expression dichotomy in carcinoma in situ and OSCC lesions using immunofluorescence microscopy and flow cytometry. The proportion of hBD-3/hBD-2 levels in non-invasively collected lesional cells compared to contralateral normal cells, obtained by ELISA, generates the beta-defensin index (BDI). Proof-of-principle and blinded discovery studies demonstrate that BDI discriminates OSCC from benign lesions. A multi-center validation study shows sensitivity and specificity values of 98.2% (95% confidence interval [CI] 90.3-99.9) and 82.6% (95% CI 68.6-92.2), respectively. A proof-of-principle study shows that BDI is adaptable to a point-of-care assay using microfluidics. We propose that BDI may fulfill a major unmet need in low-socioeconomic countries where pathology services are lacking.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , beta-Defensinas , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/patologia , beta-Defensinas/análise , beta-Defensinas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Biomarcadores , Carcinoma de Células Escamosas de Cabeça e Pescoço
2.
Radiol Case Rep ; 19(5): 1781-1790, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38390428

RESUMO

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma of colonic origin. A repeat colonoscopy was done with no recurrence or new lesion in the colon. This case underscores the challenges associated with diagnosing biliary issues and assessing liver lesions in patients with a remote history of cancer. It raises the question of when and whether, after primary cancer treatment, it becomes safe to explore alternative diagnoses without immediately suspecting metastasis. Another significant challenge arises in ascertaining the most suitable therapeutic approaches for these patients. This is because these extremely late recurrences might be linked to an indolent, slow-growing type of tumor, but also have been linked to cancer stem cells, and as any recurrence, demands attention.

3.
Clin Imaging ; 68: 210-217, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32892106

RESUMO

OBJECTIVES: To investigate the imaging features of erlotinib-associated gastrointestinal toxicity (GT) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The electronic medical records of 157 patients with NSCLC who received erlotinib between 2005 and 2018 were retrospectively reviewed to identify patients with GT. Clinical and radiologic evidence of erlotinib-associated GT was evaluated. Imaging findings were cross-referenced with clinical presentation, management, and outcomes. RESULTS: 24 (15%) patients (16 women; median age, 68 years) with radiologic evidence of GT were identified. The median time to detection of GT on imaging was 4.5 months (range: 0-58 months). 3/24 (12.5%) patients had no clinical symptoms, but GT was radiologically identified. Erlotinib-associated GT manifested in the large bowel in either a diffuse (42%) or segmental (58%) pattern. The most common imaging finding was fluid-filled bowel (23/24, 96%). CONCLUSION: Erlotinib-associated GT was identified in 15% patients with NSCLC. Fluid-filled colon and segmental involvement were the most common imaging manifestations.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Idoso , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cloridrato de Erlotinib/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Estudos Retrospectivos , Resultado do Tratamento
4.
AJR Am J Roentgenol ; 214(5): 949-961, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32182095

RESUMO

OBJECTIVE. The purpose of this review is to provide a guide for radiologists that explains the language and format of modern genomic reports and summarizes the relevance of this information for modern oncologic imaging. CONCLUSION. Genomic testing plays a critical role in guiding oncologic therapies in the age of targeted treatments. Understanding and interpreting genomic reports is a valuable skill for radiologists involved with oncologic imaging interpretation.


Assuntos
Genômica , Oncologia , Neoplasias/diagnóstico por imagem , Neoplasias/genética , Radiologistas , Humanos
5.
Abdom Radiol (NY) ; 45(10): 3028-3035, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31754740

RESUMO

PURPOSE: To determine the frequency, imaging, and clinical manifestations of immune checkpoint inhibitor (ICI)-related colitis in cancer patients on monotherapy or combination therapy. METHODS: The electronic medical records of 1044 cancer patients who received ICIs were retrospectively reviewed to identify 48 patients who had a clinical diagnosis of immune-related colitis. Imaging studies were reviewed to identify patients with imaging manifestations of colitis. Demographic data, type of ICIs, symptoms, presence of other immune-related adverse events (irAEs), and management were recorded. RESULTS: There was imaging evidence of immune-related colitis in 34 patients (24 men; median age: 63.5 years). The median time to onset of colitis was 75 days (IQR 25-75, 49.5-216 days) in patients receiving monotherapy (group 1) and 78 days (IQR 25-75, 44.3-99.5 days) in patients undergoing combination therapy (group 2) following start of ICI. Symptoms included diarrhea (91.1% [31 of 34]), nausea/vomiting (52.9% [18 of 34]), and abdominal pain (52.9% [18 of 34]). The most common imaging findings were bowel wall thickening (97% [33 of 34]) and fluid-filled colon (82.3% [28 of 34]). Colitis was diffuse in 21 of 34 (61.8%) patients. Imaging manifestations did not differ between the two groups (p > 0.05). Steroids and antibiotics were used to treat colitis in 29 of 34 (85.2%) and 13 of 34 (38.2%) patients, respectively. No patients in group 1 experienced concurrent irAEs, but 5 of 18 (27.8%) of patients in group 2 had other irAEs (p = 0.046). CONCLUSION: Immune-related colitis occurred in 3.3% of patients receiving ICIs with bowel wall thickening, fluid-filled colon and pancolitis being the most common imaging manifestations. Imaging manifestations did not differ between patients receiving monotherapy or combination therapy. However, concurrent irAEs were significantly observed in patients undergoing combination therapy.


Assuntos
Colite , Neoplasias , Colite/induzido quimicamente , Colite/diagnóstico por imagem , Terapia Combinada , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
6.
OTO Open ; 3(2): 2473974X19850752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428727

RESUMO

OBJECTIVE: To examine the diagnostic value of the sentinel lymph node biopsy in pediatric through young adult head and neck melanocytic tumors of unknown malignant potential. STUDY DESIGN: Retrospective case series. SETTING: Single academic institution. SUBJECTS AND METHODS: Demographics, histology, and outcomes were examined in 14 patients aged 4 to 24 years with head and neck melanocytic tumors of unknown malignant potential. Information on age at diagnosis, primary lesion characteristics, and sentinel lymph node biopsy were compared. RESULTS: Of 14 patients meeting criteria for head and neck melanocytic tumors of unknown malignant potential, 8 patients underwent sentinel lymph node biopsy (57%). Of those, 4 biopsies (50%) had positive sentinel nodes. All patients undergoing sentinel lymph node biopsy had primary lesions greater than 1 mm depth or mitotic rate of at least 1 mitosis per mm2. No patients had recurrence of their primary lesion at time of follow-up. CONCLUSION: Our data show a high rate of node-positive sentinel lymph node biopsy for pediatric and young adult head and neck patients with melanocytic tumors of unknown malignant potential, supporting the value of sentinel lymph node biopsy in this population.

7.
AJR Am J Roentgenol ; 213(5): W194-W210, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414888

RESUMO

OBJECTIVE. The purpose of this article is to provide a primer for radiologists focused on integrating the radiologic, pathologic, and clinical features of primary mediastinal large B-cell lymphoma (PMLBCL). CONCLUSION. PMLBCL is a unique subtype of lymphoma that poses diagnostic and therapeutic challenges to the fields of radiology and oncology. Knowledge of this distinctive clinical-pathologic entity and its associated imaging and clinical features is critical for radiologists.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Humanos , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/reabilitação
8.
Sci Rep ; 7(1): 447, 2017 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-28348370

RESUMO

Successful tissue repair requires the activities of myeloid cells such as monocytes and macrophages that guide the progression of inflammation and healing outcome. Immunoregenerative materials leverage the function of endogenous immune cells to orchestrate complex mechanisms of repair; however, a deeper understanding of innate immune cell function in inflamed tissues and their subsequent interactions with implanted materials is necessary to guide the design of these materials. Blood monocytes exist in two primary subpopulations, characterized as classical inflammatory or non-classical. While classical monocytes extravasate into inflamed tissue and give rise to macrophages or dendritic cells, the recruitment kinetics and functional role of non-classical monocytes remains unclear. Here, we demonstrate that circulating non-classical monocytes are directly recruited to polymer films within skin injuries, where they home to a perivascular niche and generate alternatively activated, wound healing macrophages. Selective labeling of blood monocyte subsets indicates that non-classical monocytes are biased progenitors of alternatively activated macrophages. On-site delivery of the immunomodulatory small molecule FTY720 recruits S1PR3-expressing non-classical monocytes that support vascular remodeling after injury. These results elucidate a previously unknown role for blood-derived non-classical monocytes as contributors to alternatively activated macrophages, highlighting them as key regulators of inflammatory response and regenerative outcome.


Assuntos
Macrófagos/patologia , Monócitos/patologia , Lesões dos Tecidos Moles/patologia , Células-Tronco/patologia , Cicatrização , Transferência Adotiva , Animais , Antígenos CD/metabolismo , Arteríolas/efeitos dos fármacos , Arteríolas/metabolismo , Materiais Biocompatíveis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Cloridrato de Fingolimode/farmacologia , Implantes Experimentais , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Modelos Biológicos , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Pele/irrigação sanguínea , Pele/patologia , Cicatrização/efeitos dos fármacos
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