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1.
Anticancer Res ; 41(9): 4417-4422, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34475063

RESUMEN

BACKGROUND/AIM: Ovarian carcinoma is the fifth leading cause of cancer-related deaths in women in the United States. Serous papillary carcinoma is the most common histological type of ovarian carcinoma that often goes undetected until it has spread within the pelvis and abdomen leading to poor prognosis. Translation of next-generation sequencing (NGS) technology into personalized medicine and identification of new potential targets for therapeutic applications may be helpful. CASE REPORT: We report a case of a 59-year-old female who initially presented in the emergency department with increasing abdominal girth, and bloating. Computed tomography showed ascites and omental and pelvic masses. Fine needle biopsy of the omental mass showed high-grade papillary adenocarcinoma consistent with high-grade ovarian serous carcinoma. She was treated with chemotherapy followed by debulking surgery. Primary ovarian serous carcinoma and synchronous primary fallopian tube serous carcinoma with multiple leiomyomas were identified in the surgical specimen. Pleural biopsy was also positive for carcinoma. NGS and programmed death-ligand 1 (PD-L1) expression testing were performed in the ovarian serous carcinoma. The results showed mutations of breast cancer type 1 (BRCA1) and type 2 (BRCA2), tumor protein p53 (TP53) (c.524G>A at pR175H), and heat shock protein 90 alpha family class B member 1 (HSP90AB1) (p.R456C), as well as low RNA expression score of PD-L1. CONCLUSION: Identification of these mutations and PD-L1 abnormality at the diagnosis of ovarian carcinoma may shed light for clinicians to provide targeted therapy with poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors for ovarian serous carcinoma. This is the first documented case of ovarian serous carcinoma to have found a HSP90AB1 (p.R456C) mutation.


Asunto(s)
Cistadenocarcinoma Seroso/genética , Neoplasias de las Trompas Uterinas/genética , Proteínas HSP90 de Choque Térmico/genética , Leiomiomatosis/genética , Neoplasias Primarias Múltiples/genética , Neoplasias Ováricas/genética , Biopsia con Aguja Fina , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/cirugía , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leiomiomatosis/tratamiento farmacológico , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Persona de Mediana Edad , Mutación , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Análisis de Secuencia de ADN , Tomografía Computarizada por Rayos X , Estados Unidos
2.
Diagn Cytopathol ; 2021 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-34411462

RESUMEN

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignancy, often with indolent behavior. Though most cases have a characteristic WWTR1-CAMTA1 gene fusion, a subtype of EHE with YAP1-TFE3 fusions and a distinct morphology has recently been described histologically, but no cases of YAP1-TFE3 EHE have been described in the cytology literature. We herein report on a case of YAP1-TFE3 fusion associated EHE diagnosed on fine-needle aspiration and core biopsy of a liver mass in an 18-year-old male patient who presented with synchronous lung and liver involvement. We also discuss the differential diagnosis of EHE on cytology specimens.

3.
Head Neck Pathol ; 2021 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-34342809

RESUMEN

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum and characterized by a complex and variable clinical presentation. Cases of unexpected oral syphilis presenting as non-healing ulcers are uncommonly reported. We report 3 cases (one female and two males, aged 35, 35, and 56 years, respectively) in which patients presented with non-healing oral ulcers. Biopsies revealed surface ulceration and a significant neutrophilic infiltrate rather than the more conventional plasma cell infiltrate seen with most reported syphilis infections, potentially leading to an inaccurate diagnosis. Treponema pallidum immunohistochemistry highlighted spirochetes within the epithelium, with additional diagnostic confirmation by serum T. pallidum particle agglutination assay. Sexual history documentation by the clinician with nonspecific oral ulcers is paramount to aiding diagnosis and leading to proper management. Further, it is important to perform immunohistochemistry for T. pallidum in oral biopsies from non-healing ulcers, especially when clinical history raises the differential diagnosis or when other clinical manifestations may support this consideration.

4.
Artículo en Inglés | MEDLINE | ID: mdl-34237726

RESUMEN

OBJECTIVES: Sinonasal hamartomas are benign neoplasms composed of disorganized mature tissue elements. Epithelial variants include respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma (SMH). Malignant transformation of REAH is rarely reported; however, the malignant transformation of SMH to adenocarcinoma has not been described. We report the first case of a transformation from SMH to adenocarcinoma. METHODS: The medical records of a patient presenting with sinonasal SMH with malignant transformation to adenocarcinoma were reviewed. The NCBI database was queried for the literature regarding SMH and malignant transformation of sinonasal hamartomas. RESULTS: A 39-year-old man presented with a left nasal mass, nasal obstruction, and epistaxis. Computed tomography and magnetic resonance imaging demonstrated a nonaggressive and heterogeneous left nasal mass with involvement of the middle turbinate and posterior ethmoid sinuses. He underwent endoscopic sinus surgery with complete excision of the mass. Pathology revealed SMH with focal areas of transition to low-grade adenocarcinoma characterized by stromal invasion but no bony, perineural, or lymphovascular invasion. Adjuvant treatment was not recommended. Literature review revealed no reported cases of malignant transformation of SMH. CONCLUSION: We report the first case of malignant transformation of SMH. Patients with SMH must be counseled that there is an extremely rare and potentially unrecognized risk of malignancy that may influence treatment and postoperative monitoring.

5.
Anticancer Res ; 41(7): 3639-3642, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34230161

RESUMEN

BACKGROUND: While it is not uncommon in patients with head and neck cancer to present with multiple metachronous primary neoplasms, rarely do these present as a singular mass composed of intertwined, histologically distinct malignant tumors. Sometimes referred to as collision tumors, these entities are poorly understood and only appear in a handful of case studies in the literature. CASE REPORT: Here we present a 58-year-old male diagnosed with a human papillomavirus-related collision tumor consisting of oropharyngeal squamous cell carcinoma and small-cell neuroendocrine carcinoma, as well as an incidentally discovered metastatic thyroid papillary carcinoma, despite an unremarkable thyroid gland. The patient underwent transoral robotic base-of-tongue resection and partial pharyngectomy with selective neck dissection followed by chemoradiotherapy. At the 18-month follow-up the patient was doing well. His thyroid was normal and no recurrent or metastatic carcinoma was identified on the computed tomography and positron-emission tomography/computed tomography imaging findings. CONCLUSION: To the best of our knowledge, this is the first such case in English literature. This case demonstrates the importance of tumor morphology and immunohistochemical testing in HPV-related oropharyngeal carcinomas, despite the overall good prognosis of such tumors, due to the possibility of synchronous or colliding primary neoplasms.


Asunto(s)
Carcinoma Neuroendocrino/metabolismo , Carcinoma de Células Escamosas/patología , Infecciones por Papillomavirus/patología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Neoplasias de la Lengua/patología , Carcinoma Neuroendocrino/virología , Carcinoma de Células Escamosas/virología , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Cáncer Papilar Tiroideo/virología , Glándula Tiroides/patología , Glándula Tiroides/virología , Neoplasias de la Tiroides/virología , Lengua/patología , Lengua/virología , Neoplasias de la Lengua/virología
6.
PLoS One ; 16(6): e0251449, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34077443

RESUMEN

BACKGROUND: Hypogonadism is reported to occur in non-alcoholic fatty liver disease (NAFLD), but earlier studies used low-sensitivity diagnostic techniques (CT, ultrasound), for NAFLD diagnosis. We hypothesized that if hypogonadism was due to NAFLD, and not solely attributable to underlying obesity/diabetes, it would be more severe in the presence of steatohepatitis (NASH). To examine the influence of liver disease on testosterone in males with type 2 diabetes mellitus (T2DM), we used gold-standard liver imaging with MR-spectroscopy (1H-MRS), and performed liver biopsies to grade/stage the NAFLD. METHODS: In this cross-sectional study, we measured in 175 males with T2DM total and free testosterone, markers of insulin resistance, and intrahepatic triglyceride content (IHTG) by 1H-MRS. Those with NAFLD on imaging underwent a liver biopsy. RESULTS: Total testosterone was higher in the group without NAFLD ("No-NAFLD"; n = 48) compared to isolated steatosis (IS; n = 62) or NASH (n = 65) (385 ± 116 vs. 339 ± 143 vs. 335 ± 127 ng/ml, ptrend 0.03). Testosterone was also lower in obese vs. non-obese subjects in both the No-NAFLD and IS groups (p = 0.06 and p = 0.11, respectively), but not in obese vs. non-obese patients with NASH (p = 0.81). IHTG was independently associated with total testosterone (ß = -4.8, p = 0.004). None of the liver histology characteristics were associated with lower testosterone. CONCLUSIONS: NAFLD is linked to lower total testosterone in patients with T2DM, but likely given a common soil of insulin resistance/obesity and not from the severity of liver necroinflammation or fibrosis. Nevertheless, clinicians should consider screening patients with T2DM and NAFLD for hypogonadism.

7.
Int J Gynecol Pathol ; 40(4): 383-390, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33560745

RESUMEN

Primary ovarian melanoma arising from ovarian teratomas are rarely reported and difficult to accurately diagnose. Cases in the literature rely on a diagnosis of exclusion, and cases of primary ovarian melanoma with pathologic evidence of melanoma in situ are exceedingly rare. We report a case of a 66-yr-old female who presented to emergency department with abdominal pain and bloating. Computed tomography scan showed a 21 cm complex pelvic mass. An urgent laparoscopic bilateral salpingo-oophorectomy was performed. Pathologically the mass was identified as a mature teratoma. Within the cystic teratoma, there was an area showing a sheet arrangement of atypical cells. Those atypical cells were positive for Melan A, Sox10, HMB45, and c-KIT, and negative for PD-L1. Melanoma in situ was present in both the squamous and ciliated columnar epithelium. The melanoma was negative for PD-L1, and no BRAF (codon 600, exons 11, 14, and 15) or c-KIT (exons 2, 9, 10, 11, 13, 14, 15, 17, 18) mutations were identified, thus supporting the so-called triple negative malignant melanoma. A thorough dermatologic exam was conducted and only a 3 mm skin basal cell carcinoma was confirmed on biopsy. At 11 mo of follow-up, the patient is disease free and doing well and no metastatic melanoma has been identified. To the best of our knowledge, this is the first documented case of a primary ovarian melanoma arising in a mature teratoma with evidence of melanoma in situ present in both ciliated columnar and squamous epithelium in a patient with synchronous skin basal cell carcinoma. Our case is positive for c-KIT protein (CD117) by immunohistochemistry, but negative for KIT mutation. More case reports are needed to further characterize the disease.


Asunto(s)
Carcinoma Basocelular/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Melanoma/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico por imagen , Proteínas Proto-Oncogénicas c-kit/metabolismo , Teratoma/diagnóstico por imagen , Anciano , Carcinoma Basocelular/patología , Carcinoma Basocelular/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Células Epiteliales , Epitelio/diagnóstico por imagen , Epitelio/patología , Epitelio/cirugía , Femenino , Humanos , Inmunohistoquímica , Melanoma/patología , Melanoma/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Ovario/diagnóstico por imagen , Ovario/patología , Ovario/cirugía , Pronóstico , Salpingooforectomía , Teratoma/patología , Teratoma/cirugía , Tomografía Computarizada por Rayos X
8.
Laryngoscope ; 131(1): E1-E7, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32057109

RESUMEN

OBJECTIVES: To compare the clinical characteristics of osteoma, ossifying fibroma (OF) and fibrous dysplasia (FD) in the paranasal sinus and craniofacial regions. METHODS: Totally 282 patients (112 males, 170 females) with osteoma (161), OF (44), and FD (77) involving the paranasal sinus, skull base and orbit treated surgically from January 2012 to August 2018 were analyzed retrospectively. RESULTS: For osteoma, OF and FD, the onset ages were 40.3 (6-75), 24.5 (5-62), and 15 (1-63) years, and the most common locations were ethmoid sinus (49.7%), maxilla (36.4%) and maxilla (49.4%), respectively. There were significant differences of the preoperative serum alkaline phosphatase (ALP) levels between patients with osteoma (65 [25,184] U/L), OF (85.5 [41,474] U/L), and FD (104 [39,362] U/L) (Z = 44.9, P < .05). The ALP levels of OF and FD patients were comparable between monostotic and polyostotic lesions (P > .05). The recurrent rates of osteoma, OF, and FD were 0%, 13.6%, and 15.6%, respectively. The recurrent OF cases had significantly higher ALP level than the primary ones (283.5 [108,474] U/L vs. 76 [41,348] U/L, U = 14, P < .05). CONCLUSION: There are differences in the onset age, location, and recurrence rate among osteoma, OF and FD involving the paranasal sinus and craniofacial region. Osteoma most commonly occurs in the ethmoid sinus, while OF and FD involve the maxilla most and are more likely to involve the orbit and the skull base, respectively. Endoscopic surgery is currently the main method for treatment, but individualized treatment regimen should be developed for patients. LEVEL OF EVIDENCE: IV Laryngoscope, 131:E1-E7, 2021.


Asunto(s)
Fibroma Osificante/diagnóstico , Displasia Fibrosa Ósea/diagnóstico , Órbita , Osteoma/diagnóstico , Senos Paranasales , Base del Cráneo , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
9.
Int J Surg Pathol ; 29(4): 368-377, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33289434

RESUMEN

BACKGROUND: Anaplastic thyroid carcinoma (ATC), a highly aggressive malignancy, has no effective treatment to date. Trophoblast cell-surface antigen 2 (TROP-2), a transmembrane glycoprotein, has been suggested to be a promising novel target for sacituzumab govitecan, an antibody-drug conjugate. 5-Hydroxymethylcytosine (5hmC) has a role in tumor suppression and promoting modification. Additionally, isocitrate dehydrogenase 1 (IDH1) mutations are strongly associated with increased overall survival in gliomas and worse prognosis in leukemias. This study attempts to evaluate the immunoexpression of TROP-2, 5hmC, and IDH1 in ATCs and to determine their potential impact in targeted therapy. METHODS: Twenty-four ATCs were retrieved, with 9 cases that occurred de novo and 15 cases derived from either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma (FTC). Sections were immunostained with TROP-2, 5hmC, and IDH1 antibodies, and evaluated using the QuPath program. The t tests were performed using SPSS software. RESULTS: TROP-2 was detected in 12 ATCs with 9 cases demonstrating a high expression and in all PTC components, and absent in all FTC components of secondary ATCs. 5hmC expression was moderately reduced in PTC and FTC components and markedly reduced in ATC. The entire cohort showed a total absence of IDH1. CONCLUSIONS: Increased TROP-2 immunoexpression in some ATCs supports that these patients may potentially benefit from an antibody-drug conjugate therapy targeting TROP-2. Markedly reduced 5hmC expression suggests that 5hmC may be used as potential therapeutic targets for ATC. The total lack of IDH1 R132H mutation by immunostain indicates that it has no prognostic and therapeutic value in ATC.

10.
Anticancer Res ; 40(12): 7053-7056, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33288602

RESUMEN

BACKGROUND: The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. CASE REPORT: We report such a case of a 67-year-old male smoker with a history of laryngeal squamous cell carcinoma. He was incidentally identified through follow up computed tomography to have three masses in the lung, rectum and jejunum, respectively. Biopsies were performed and demonstrated synchronous lung small cell carcinoma (pT1bN0) and rectal adenocarcinoma. The patient underwent fractionated stereotactic radiation (FSRT) to the pulmonary tumor and chemotherapy with cisplatin and etoposide followed by laparoscopic rectum low anterior resection and small bowel segmental resection. Final pathology diagnoses confirmed synchronous microsatellite stable (MMS) moderately differentiated adenocarcinoma of the rectum (pT3N1b) and jejunal gastrointestinal stromal tumor (GIST), spindle cell type (pT2N0). At 8 months follow up postsurgery, the patient was doing well and no tumor recurrences were identified. CONCLUSION: To the best of our knowledge, this is the first documented case of synchronous primary small cell lung carcinoma, rectal adenocarcinoma, and GIST in the English literature. The rarity, diagnosis and treatment challenges of these entities are discussed.


Asunto(s)
Adenocarcinoma/etiología , Tumores del Estroma Gastrointestinal/etiología , Yeyuno/patología , Neoplasias Laríngeas/complicaciones , Neoplasias del Recto/etiología , Carcinoma Pulmonar de Células Pequeñas/etiología , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Adenocarcinoma/patología , Anciano , Tumores del Estroma Gastrointestinal/patología , Humanos , Neoplasias Laríngeas/patología , Masculino , Neoplasias del Recto/patología , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología
11.
Front Immunol ; 11: 1952, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32922402

RESUMEN

TH17 cells have been extensively investigated in inflammation, autoimmune diseases, and cancer. The precise molecular mechanisms for TH17 cell regulation, however, remain elusive, especially regulation at the post-transcriptional level. Tristetraprolin (TTP) is an RNA-binding protein important for degradation of the mRNAs encoding several proinflammatory cytokines. With newly generated T cell-specific TTP conditional knockout mice (CD4CreTTPf/f), we found that aging CD4CreTTPf/f mice displayed an increase of IL-17A in serum and spontaneously developed chronic skin inflammation along with increased effector TH17 cells in the affected skin. TTP inhibited TH17 cell development and function by promoting IL-17A mRNA degradation. In a DSS-induced colitis model, CD4CreTTPf/f mice displayed severe colitis and had more TH17 cells and serum IL-17A compared with wild-type mice. Furthermore, neutralization of IL-17A reduced the severity of colitis. Our results reveal a new mechanism for regulating TH17 function and TH17-mediated inflammation post-transcriptionally by TTP, suggests that TTP might be a novel therapeutic target for the treatment of TH17-mediated diseases.


Asunto(s)
Colitis/metabolismo , Colon/metabolismo , Interleucina-17/sangre , Células Th17/metabolismo , Tristetraprolina/metabolismo , Animales , Antiinflamatorios/farmacología , Anticuerpos Neutralizantes/farmacología , Colitis/inducido químicamente , Colitis/inmunología , Colitis/prevención & control , Colon/efectos de los fármacos , Colon/inmunología , Colon/patología , Dermatitis/inmunología , Dermatitis/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Humanos , Interleucina-17/genética , Células Jurkat , Ratones Endogámicos C57BL , Ratones Noqueados , Estabilidad del ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal , Células Th17/efectos de los fármacos , Células Th17/inmunología , Tristetraprolina/deficiencia , Tristetraprolina/genética
12.
Anticancer Res ; 40(10): 5411-5416, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32988861

RESUMEN

BACKGROUND: Patients with inflammatory bowel disease have markedly increased risk for developing colitis-associated colorectal adenocarcinoma (CAC). There is no established prognostic biomarker for CAC. MATERIALS AND METHODS: A retrospective study was performed on a cohort of 57 CACs. Expression of caudal type homeobox transcription factor 2 (CDX2) and YES-associated protein 1 (YAP1) expression was correlated with clinicodemographic and histopathological features. RESULTS: Neither YAP1 nor CDX2 expression alone was significantly associated with tumor invasion beyond the muscularis propria or lymph node status. However, a subgroup of CAC with double negativity for expression of YAP1 and CDX2 was more frequently found in younger patients, and more frequently associated with higher pathological tumor stage and nodal metastasis. Furthermore, a positive correlation between CDX2 and YAP1 expression was identified in CAC and sporadic colorectal adenocarcinoma. CONCLUSION: Our study demonstrates that double negativity for expression of YAP1 and CDX2 defines a subgroup of CAC with early onset and aggressive clinical features.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Factor de Transcripción CDX2/genética , Colitis/genética , Neoplasias Colorrectales/genética , Factores de Transcripción/genética , Adenocarcinoma/complicaciones , Adenocarcinoma/genética , Adenocarcinoma/patología , Adulto , Biomarcadores de Tumor/genética , Colitis/complicaciones , Colitis/patología , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/patología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/patología , Masculino , Persona de Mediana Edad , Pronóstico
13.
ACS Appl Mater Interfaces ; 12(36): 40031-40041, 2020 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-32805826

RESUMEN

Light-mediated remote control of stem cell fate, such as proliferation, differentiation, and migration, can bring a significant impact on stem cell biology and regenerative medicine. Current UV/vis-mediated control approaches are limited in terms of nonspecific absorption, poor tissue penetration, and phototoxicity. Upconversion nanoparticle (UCNP)-based near-infrared (NIR)-mediated control systems have gained increasing attention for vast applications with minimal nonspecific absorption, good penetration depth, and minimal phototoxicity from NIR excitations. Specifically, 808 nm NIR-responsive upconversion nanomaterials have shown clear advantages for biomedical applications owing to diminished heating effects and better tissue penetration. Herein, a novel 808 nm NIR-mediated control method for stem cell differentiation has been developed using multishell UCNPs, which are optimized for upconverting 808 nm NIR light to UV emission. The locally generated UV emissions further toggle photoswitching polymer capping ligands to achieve spatiotemporally controlled small-molecule release. More specifically, with 808 nm NIR excitation, stem cell differentiation factors can be released to guide neural stem cell (NSC) differentiation in a highly controlled manner. Given the challenges in stem cell behavior control, the developed 808 nm NIR-responsive UCNP-based approach to control stem cell differentiation can represent a new tool for studying single-molecule roles in stem cell and developmental biology.


Asunto(s)
Nanopartículas/química , Células-Madre Neurales/efectos de los fármacos , Polímeros/farmacología , Dióxido de Silicio/farmacología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Humanos , Rayos Infrarrojos , Tamaño de la Partícula , Procesos Fotoquímicos , Polímeros/química , Porosidad , Dióxido de Silicio/química , Propiedades de Superficie
14.
Anticancer Res ; 40(8): 4401-4404, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32727769

RESUMEN

BACKGROUND: The occurrence of lung adenocarcinoma metastasizing to the pancreas is overall rare and can histologically imitate primary pancreatic ductal carcinoma (PDAC). CASE REPORT: This is a case report of a 70-year-old female with a history of surgically resected right lung adenocarcinoma presenting for routine follow up without symptoms. CT scans revealed a pancreatic cystic mass with ductal dilatation that was sampled via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and thought to be a primary pancreatic mucinous neoplasm with high grade dysplasia suspicious for carcinoma based on smear cytology. On repeat EUS-FNA and biopsy (FNB) with additional immunohistochemical testing for lung adenocarcinoma markers thyroid transcription factor (TTF1) and Napsin A and molecular testing, the lesion was identified as a metastasis of lung adenocarcinoma with an epidermal growth factor receptor (EGFR L858R) mutation; subsequently, the patient underwent targeted therapy that yielded an almost complete response. CONCLUSION: To the best of our knowledge, this is the first documented case in English literature of a lung adenocarcinoma metastasis to the pancreas mimicking a pancreatic primary neoplasm and highlights the potential pitfalls of EUS-FNA for the diagnosis of certain metastases to the pancreas.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pancreáticas/secundario , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Anciano , Biomarcadores/metabolismo , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Diagnóstico Diferencial , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Receptores ErbB/genética , Femenino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Mutación , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Tomografía Computarizada por Rayos X
15.
Anticancer Res ; 40(7): 4029-4032, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32620648

RESUMEN

The synchronous diagnosis of two or more primary malignancies in a patient is overall rare. This is a case report of a 70-year-old female with a history of skin squamous cell carcinoma presenting with occult hematochezia. Colonoscopy and biopsy results confirmed a microsatellite stable (MMS) adenocarcinoma in the ascending colon, and subsequent computed tomography (CT) scans identified a 3.2 cm right colonic mass and a 5.0 cm mass in the pancreatic body. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) confirmed the presence of pancreatic ductal adenocarcinoma (PDAC). The patient underwent neo-adjuvant FOLFIRINOX (folinic acid, fluorouracil, irinotecan and oxaliplatin) chemotherapy prior to the simultaneous distal pancreatectomy and right hemicolectomy for both pancreatic and colonic tumors. The pathology diagnoses included moderately differentiated pancreatic ductal carcinoma (PDAC) with histiocyte-like features (tumor stage: ypT3N1M0) and moderately differentiated colonic adenocarcinoma, intestinal type (tumor stage: ypT3N0M0). To the best of our knowledge, this is the first documented case of synchronous primary colonic adenocarcinoma and PDAC in the English literature.


Asunto(s)
Adenocarcinoma/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias del Colon/diagnóstico , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma/patología , Anciano , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/patología , Carcinoma de Células Escamosas , Neoplasias del Colon/patología , Femenino , Fluorouracilo/uso terapéutico , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Neoplasias Primarias Múltiples/patología , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/patología , Neoplasias Cutáneas
16.
World J Gastrointest Pharmacol Ther ; 11(2): 25-39, 2020 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-32550043

RESUMEN

BACKGROUND: In order to improve risk stratification and clinical management of the pancreatic ductal adenocarcinoma (PDAC), the American Joint Committee on Cancer (AJCC) has published its eighth edition staging manual. Some major changes have been introduced in the new staging system for both T and N categories. Given the rarity of resectable disease, distal pancreatic cancer is likely underrepresented in the published clinical studies, and how the impact of the staging system actually reflects on to clinical outcomes remain unclear. AIM: To validate the AJCC 8th edition of TNM staging in distal PDAC. METHODS: A retrospective cohort study was performed in seven academic medical centers in the United States. Clinicopathological prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were evaluated through univariate and multivariate analyses. RESULTS: Overall, 454 patients were enrolled in the study, and were divided into 2 subgroups: Invasive intraductal papillary mucinous neoplasms (IPMN) (115 cases) and non-IPMN associated adenocarcinoma (339 cases). Compared to invasive IPMN, non-IPMN associated adenocarcinomas are more common in relatively younger patients, have larger tumor size, are more likely to have positive lymph nodes, and are associated with a higher tumor (T) stage and nodal (N) stage, lymphovascular invasion, perineural invasion, tumor recurrence, and a worse PFS and OS. The cohort was predominantly categorized as stage 3 per AJCC 7th edition staging manual, and it's more evenly distributed based on 8th edition staging manual. T and N staging of both 7th and 8th edition sufficiently stratify PFS and OS in the entire cohort, although dividing into N1 and N2 according to the 8th edition does not show additional stratification. For PDAC arising in IPMN, T staging of the 7th edition and N1/N2 staging of the 8th edition appear to further stratify PFS and OS. For PDAC without an IPMN component, T staging from both versions fails to stratify PFS and OS. CONCLUSION: The AJCC 8th edition TNM staging system provides even distribution for the T staging, however, it does not provide better risk stratification than previous staging system for distal pancreatic cancer.

17.
Gastroenterol Rep (Oxf) ; 8(1): 50-55, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32467761

RESUMEN

Background: Nivolumab and pembrolizumab-two monoclonal antibodies that block human programmed cell death-1 (PD-1)-have been successfully used to treat patients with multiple advanced malignancies. The histologic patterns of hepatic toxicity induced by anti-PD-1 treatment have not been well studied and the aim of this study was to explore them. Methods: Eight patients with advanced malignancies who were treated with either nivolumab or pembrolizumab were identified from five institutions. These patients had no history of underlying liver disease and a viral hepatitis panel was negative in all patients. Results: Seven of eight patients exhibited mild to moderate gastrointestinal symptoms such as abdominal pain, fatigue, nausea, vomiting, and jaundice after anti-PD-1 treatment. Significant elevations in liver-chemistry tests were detected in all patients. Six cases (6/8) demonstrated an acute lobular hepatitis pattern of histologic injury. The remaining two cases showed different histologic patterns of injury: steatohepatitis with mild cholestasis (1/8) and pure acute cholestatic injury (1/8). No case showed typical features of autoimmune hepatitis. The liver function recovered in all eight cases after cessation of anti-PD-1 agents and with immunosuppressive therapy. Conclusions: Our study suggests that screening patients for abnormal liver-function tests prior to anti-PD-1 therapy as well as periodic monitoring of liver-function tests are necessary to prevent severe liver injury. Rather than causing classical autoimmune hepatitis, PD-1 inhibitors appear to produce an immune-mediated nonspecific acute hepatitis. Drug cessation, without steroid therapy, may therefore be sufficient in some patients.

18.
Gastroenterology Res ; 13(2): 81-84, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32362967

RESUMEN

Diagnosis of Epstein-Barr virus (EBV)-associated hepatitis, chronic active EBV infection, and EBV-associated lymphoproliferative diseases, is always challenging due to the overlapping symptoms and lack of diagnostic criteria. We report such a case of a 40-year-old man with unremarkable past medical history. He presented with fever of unknown origin for 1 month with jaundice for 2 days. Physical exams were unremarkable with body temperature at 98.6 °F. His liver function tests were elevated with alanine transaminase (ALT) 559 U/L, aspartate transaminase (AST) 892 U/L, alkaline phosphatase 319 U/L and total bilirubin 4.4 mg/dL. Computed tomography of his chest, abdomen and pelvis did not show lymphadenopathy or hepatosplenomegaly. A liver biopsy showed moderately acute hepatitis with hemophagocytosis, positive Epstein-Barr virus encoding RNA (EBER) in situ hybridization in CD3 and CD4-positive T cells and CD56-positive natural killer (NK) cells. CD20 was negative. The pathology diagnosis was consistent with reactivation of EBV hepatitis but NK-cell lymphoma needs to be excluded. Steatohepatitis with mild activity was present. His blood EBV DNA was 846,000 copies/mL and continued to increase to 2,000,000 copies/mL. Flow cytometric analysis of his bone marrow revealed an increased NK-cell activity but no T/NK-cell lymphoma was identified. Initial treatment with rituxan, etoposide and/or ruxolitinib/acyclovir failed or only had limited effect. However, subsequent valganciclovir greatly improved his conditions. In his 3 months follow-up, the patient was doing well with almost normal liver function tests except mildly elevated ALT (95 U/L) that was due to mild steatohepatitis. EBV DNA PCR was 2,009 copies/mL. To the best of our knowledge, this is the first documented case with reactivation of EBV hepatitis mimicking NK-cell lymphoma in the English literature. With appropriate anti-EBV viral treatments, the patient eventually became asymptomatic and was able to return to his routine life.

19.
J Nutr Biochem ; 81: 108381, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32422424

RESUMEN

One-carbon metabolism is a collection of metabolic cycles that supports methylation and provides one-carbon bound folates for the de novo synthesis of purine and thymidine nucleotides. The methylation of phosphatidylethanolamine to form choline has been extensively studied in the context of fatty liver disease. However, the role of one-carbon metabolism in supporting nucleotide synthesis during liver damage has not been addressed. The objective of this study is to determine how the disruption of one-carbon metabolism influences nucleotide metabolism in the liver after dietary methionine and choline restriction. Mice (n=8) were fed a methionine-choline-deficient or control diet for 3 weeks. We treated mice with the compound alloxazine (0.5 mg/kg), a known adenosine receptor antagonist, every second day during the final week of feeding to probe the function of adenosine signaling during liver damage. We found that concentrations of several hepatic nucleotides were significantly lower in methionine- and choline-deficient mice vs. controls (adenine: 13.9±0.7 vs. 10.1±0.6, guanine: 1.8±0.1 vs. 1.4±0.1, thymidine: 0.0122±0.0027 vs. 0.0059±0.0027 nmol/mg dry tissue). Treatment of alloxazine caused a specific decrease in thymidine nucleotides, decrease in mitochondrial content in the liver and exacerbation of steatohepatitis as shown by the increased hepatic lipid content and altered macrophage morphology. This study demonstrates a role for one-carbon metabolism in supporting de novo nucleotide synthesis and mitochondrial function during liver damage.


Asunto(s)
Carbono/metabolismo , Hígado Graso/metabolismo , Macrófagos/metabolismo , Mitocondrias/metabolismo , Nucleótidos/metabolismo , Adenosina/metabolismo , Animales , Colina/farmacología , Deficiencia de Colina/metabolismo , Dieta , Modelos Animales de Enfermedad , Flavinas/farmacología , Guanidina/metabolismo , Inflamación/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Metionina/deficiencia , Metionina/farmacología , Ratones , Ratones Endogámicos C57BL , Antagonistas de Receptores Purinérgicos P1/farmacología , Timidina/metabolismo
20.
Anticancer Res ; 40(4): 2225-2229, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32234918

RESUMEN

BACKGROUND: Primary hepatic carcinosarcoma is a rare subtype of liver malignancy, with only a small number of cases described in the English literature. CASE REPORT: We report the case of a 72-year-old man with a history of hepatitis C, who presented with complaints of abdominal pain. The patient's alpha fetoprotein (AFP) level was highly elevated at 7,406 ng/ml. His albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels were within normal ranges. Computer tomographic scans discovered a 12×9×8 cm mass in the left lobe of the liver, extending to the anterior gastric wall. A partial hepatectomy of segments 2 and 3 with en bloc distal gastrectomy and omentectomy, a Roux-en-Y gastrojejunostomy, and a cholecystectomy were performed. Pathology revealed the mass to be a hepatic carcinosarcoma composed of collision tumor of four malignant components: hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma and rhabdomyosarcoma. One and half month post-surgery, the patient was found to have a mass confirmed by biopsy as hepatocellular carcinoma in the right lobe, nodules in his lung and bone, and his AFP level elevated to 51,027.6 ng/ml. He died after two months during hospice care. CONCLUSION: To the best of our knowledge, this is the first documented case of primary hepatic carcinosarcoma with collision tumor of four malignant entities (hepatocellular carcinoma, cholangiocarcinoma, osteosarcoma and rhabdomyosarcoma). The pathogenesis, diagnosis, treatment and prognosis of this disease are discussed.


Asunto(s)
Carcinoma Hepatocelular/parasitología , Carcinosarcoma/patología , Colangiocarcinoma/patología , Neoplasias Hepáticas/patología , Hígado/patología , Anciano , Neoplasias de los Conductos Biliares/diagnóstico por imagen , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/cirugía , Biopsia/métodos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Carcinosarcoma/diagnóstico por imagen , Carcinosarcoma/cirugía , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/cirugía , Colecistectomía/métodos , Resultado Fatal , Gastrectomía/métodos , Derivación Gástrica/métodos , Hepatectomía/métodos , Humanos , Hígado/diagnóstico por imagen , Hígado/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Masculino , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/patología , Osteosarcoma/cirugía , Pronóstico , Rabdomiosarcoma/diagnóstico por imagen , Rabdomiosarcoma/patología , Rabdomiosarcoma/cirugía , Tomografía Computarizada por Rayos X , alfa-Fetoproteínas/metabolismo
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