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1.
Pathobiology ; : 1-11, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354152

RESUMO

BACKGROUND: Invasive breast carcinoma with a choriocarcinomatous pattern (IBC-CP) is extremely rare, and its molecular basis is yet unclear. The choriocarcinomatous pattern is characterized by the biphasic arrangement of multinucleated syncytiotrophoblast-like cells around clusters of monotypic tumor cells in a hemorrhagic background, along with ß-human chorionic gonadotropin (ß-hCG) expression. The differentiation of IBC-CP from metastatic choriocarcinoma of the breast (MC-B) is difficult due to the histologic similarity. METHODS: Based on a literature review and our own case, the clinicopathologic differences between IBC-CP patients (n = 17) and MC-B patients (n = 8) were analyzed. Moreover, in our case of IBC-CP, next-generation sequencing (NGS) comparative analysis was conducted for both choriocarcinomatous and invasive breast carcinoma (IBC) components. RESULTS: Compared to the MC-B patients, the IBC-CP patients were older (p < 0.001) and less frequently had past histories of gestational trophoblastic disease/pregnancy/abortion (p = 0.001) and distant metastases (p = 0.005). Our case, a 49-year-old female patient, presented with masses in the right breast and axilla. Following neoadjuvant chemotherapy, a radical mastectomy found an 8.5-cm-sized tumor. Microscopically, multinucleated syncytiotrophoblast-like cells were observed around mononuclear tumor cells with hemorrhage and necrosis. Some tumor cells showed ß-hCG immunopositivity, which was compatible with IBC-CP. NGS results showed a missense mutation in exon 5 of the TP53 gene in both the choriocarcinomatous and IBC components. Meanwhile, copy number loss in the PTEN gene was only identified in the choriocarcinomatous components. CONCLUSION: The present IBC-CP case is triple-negative breast cancer with TP53 mutation. The PTEN gene may be associated with choriocarcinomatous differentiation. Obtaining a medical history is mandatory to exclude metastatic lesions.

2.
Gut ; 71(5): 961-973, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33849943

RESUMO

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.


Assuntos
Deficiência Intelectual , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Talassemia alfa , Proteínas Correpressoras/genética , Genes Homeobox , Proteínas de Homeodomínio , Humanos , Deficiência Intelectual/genética , Chaperonas Moleculares/genética , Recidiva Local de Neoplasia/genética , Tumores Neuroendócrinos/genética , Proteínas Nucleares/genética , Neoplasias Pancreáticas/patologia , Telômero/genética , Telômero/patologia , Fatores de Transcrição/genética , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/genética
3.
Clin EEG Neurosci ; 53(3): 229-237, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34255579

RESUMO

Background and Purpose. Although acute meningitis and encephalitis are known to cause cognitive dysfunction, the prognostic values of neuropsychological and neurophysiological tests in predicting clinical outcomes are seldom studied. We investigated specific neurocognitive dysfunction and event-related potentials (ERPs), which can predict functional outcomes in patients with acute meningitis and encephalitis. Methods. We enrolled consecutive adult patients with acute meningitis and encephalitis and performed neuropsychological tests and ERP studies using a passive auditory oddball paradigm at enrollment. Patient functional outcomes were assessed using the Glasgow Outcome Scale at 6 (GOS6) months after discharge. Results. Twenty-two patients were included in the study. Among 21 patients who performed neuropsychological tests, Korean-Trail Making Test-Elderly's version, Part A time (TMT-A time) correlated with GOS6, which remained significant even after controlling for age. We identified a significant association between TMT-A time and P3a latency. Post-hoc analysis showed that patients with longer TMT-A time (≥23 s) tended to have longer P3a latency than those with shorter TMT-A time. Conclusions. Decreased psychomotor speed predicted poor clinical outcomes. Because TMT-A time can be performed at the bedside in a relatively short time, this might be a useful neuropsychological biomarker to predict or monitor clinical outcomes. Furthermore, passive oddball P3a may be useful in patients with more severe disease who are unable to perform the TMT task.


Assuntos
Disfunção Cognitiva , Encefalite , Meningite , Adulto , Idoso , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Eletroencefalografia/efeitos adversos , Humanos , Meningite/complicações , Testes Neuropsicológicos
4.
Pathobiology ; 89(1): 49-55, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34515187

RESUMO

BACKGROUND: Endoscopic ultrasound-guided ablation (EUS-A) therapy is a minimally invasive procedure for pancreatic-cystic tumors in patients with preoperative comorbidities or in patients who are not indicated for surgical resection. However, histopathologic characteristics of pancreatic cysts after ablation have not been well-elucidated. METHODS: Here, we analyzed pathological findings of 12 surgically resected pancreatic cysts after EUS-A with ethanol and/or paclitaxel injection. RESULTS: Mean patient age was 49.8 ± 13.6 years with a 0.3 male/female ratio. Clinical impression before EUS-A was predominantly mucinous cystic neoplasms. Mean cyst size before and after ablation therapy was similar (3.7 ± 1.0 cm vs. 3.4 ± 1.6 cm; p = 0.139). Median duration from EUS-A to surgical resection was 18 (range, 1-59) months. Mean percentage of the residual neoplastic lining epithelial cells were 23.1 ± 37.0%. Of the resected cysts, 8 cases (67%) showed no/minimal (<5%) residual lining epithelia, while the remaining 4 cases (33%) showed a wide range of residual mucinous epithelia (20-90%). Ovarian-type stroma was noted in 5 cases (42%). Other histologic features included histiocytic aggregation (67%), stromal hyalinization (67%), diffuse egg shell-like calcification along the cystic wall (58%), and fat necrosis (8%). CONCLUSION: Above all, diffuse egg shell-like calcification along the pancreatic cystic walls with residual lining epithelia and/or ovarian-type stroma were characteristics of pancreatic cysts after EUS-A. Therefore, understanding these histologic features will be helpful for precise pathological diagnosis of pancreatic cystic tumor after EUS-A, even without knowing the patient's history of EUS-A.


Assuntos
Cisto Pancreático , Neoplasias Pancreáticas , Pseudocisto Pancreático , Adulto , Endossonografia , Etanol , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico
5.
Artigo em Inglês | MEDLINE | ID: mdl-32802138

RESUMO

Hepatobiliary disease currently serves as an important public health issue due to the fact that it is one of the major causes of death among economically active individuals and can easily progress to chronic diseases. Despite the development of vaccines and numerous drugs, a definite treatment remains lacking owing to different stages of the disease itself, its intricate pathogenesis, an effect uncertainty for long-term use, resistance, and side effects. Curcuma longa (C. longa), which belongs to the family Zingiberaceae and the genus Curcuma, has long been used not only as spice for curry or dye but also as a constituent of herbal formula for the treatment of different diseases due to its bioactive activities. Recently, many studies on the experimental results of C. longa have been published relative to hepatobiliary diseases such as fatty liver, hepatitis, cirrhosis, and tumors. Therefore, in this review, we aimed to summarize the pharmacological effects and underlying molecular mechanisms of C. longa and its four compounds, ß-elemene, germacrone, ar-turmerone, and bisacurone, against hepatobiliary diseases. C. longa exhibited antioxidant, hepatoprotective, antisteatotic, anti-inflammatory, antifibrotic, antitumor, and cholagogic effects by regulating apoptosis, CYP2E1, Nrf, lipid metabolism-related factors, TGF-ß, NF-κB, CYP7A1, and so on. In particular, ß-elemene could be an attractive compound owing to its remarkable hepatoprotective, anti-inflammatory, antifibrotic, and antitumor activities. Altogether, the present review provides a preclinical basis for the efficacy of C. longa as an effective therapeutic agent for the prevention and treatment of hepatobiliary diseases, despite the need for further studies to establish the extraction conditions and separation of active constituents with high bioavailability, and warrants further evaluation in clinical trials.

6.
Pathol Res Pract ; 216(5): 152940, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32276789

RESUMO

The clinicopathological and prognostic significance of olfactomedin-4 (OLFM4) expression has not yet been elucidated in extrahepatic bile duct carcinomas (EBDCs). Immunohistochemical analysis of OLFM4 expression in 31 normal biliary epithelia, 33 biliary intraepithelial neoplasias (BilINs), and 180 surgically resected EBDCs (54 perihilar and 126 distal) was performed and was used to analyze clinicopathological variables including patient survival. The expression of OLFM4 showed a progressive increase from normal biliary epithelia (0.2 ±â€¯0.4) to BilINs (2.8 ±â€¯3.2) to EBDCs (4.6 ±â€¯4.2; P < 0.001). OLFM4 was highly expressed in 26.1% (47/180) of the EBDC cases, and high OLFM4 levels were more frequently observed in tumors with nodular growth (P = 0.029), well differentiation (P = 0.011), and lower T-category (P = 0.025) and stage grouping (P = 0.013). Patients with EBDC having high expression of OLFM4 had better survival than those with low expression of OLFM4 (median, 43.3 vs. 29.2 months; P = 0.037). OLFM4 might play an important role in carcinogenesis and in the progression from BilINs to EBDCs. High OLFM4 expression predicted less aggressive clinical behavior in patients with EBDC.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Biomarcadores Tumorais/análise , Colangiocarcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Pathology ; 52(3): 336-347, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32111396

RESUMO

Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p<0.001), as well as more prevalent lymphovascular and perineural invasion (p=0.002) and lymph node and distant metastases (p<0.001). Patients with MAcNECs had worse overall (p<0.001) and recurrence-free survival (p<0.001) than those with PanNETs, but no significant difference with those with ACCs. Subgroup analyses revealed that patients with ACCs and MAcNECs had significantly worse recurrence-free survival than those with grade 1 PanNET (p<0.001), and patients with MAcNECs also had worse overall survival than those with grade 1 and 2 PanNETs (p<0.001, and p=0.001). ACCs presented more commonly with intraductal growth (p=0.014) than MAcNECs, while MAcNECs more often had lymph node metastasis (p=0.012) than ACCs. The telomere maintenance mechanism Alternative Lengthening of Telomeres (ALT) was assessed by telomere-specific FISH, and ALT was detected in 1 of 20 ACCs and in three of the 13 MAcNECs. Patients with MAcNECs and ACCs had worse survival and more aggressive behaviour than those with grade 1 PanNETs; thus, the clinicopathological behaviour of MAcNECs resembles ACCs rather than PanNETs. Combined neuroendocrine and acinar cell immunohistochemical markers are helpful for differentiating these different tumour types.


Assuntos
Carcinoma de Células Acinares/patologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Carcinoma de Células Acinares/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade
8.
JMIR Mhealth Uhealth ; 8(3): e14435, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32159517

RESUMO

BACKGROUND: Exercise is predicted to have a positive effect among hepatocellular carcinoma (HCC) patients. However, these patients are hesitant to start and build up an exercise program for one major reason: the vague fear of developing hepatic decompensation, a potentially fatal condition that can lead to death. Integrating mobile health (mHealth) with individualized exercise programs could be a possible option for promoting physical capacity among HCC patients. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of rehabilitation exercises, which have been individually prescribed via an mHealth app, on physical fitness, body composition, biochemical profile, and quality of life among HCC patients. METHODS: A total of 37 HCC patients were enrolled in a 12-week course with an mHealth app program targeted to HCC patients. The wearable wristband device Neofit (Partron Co) was provided to participants, and recorded daily physical data, such as the number of steps, calorie expenditure, exercise time, and heart rate. Each participant was given an individualized rehabilitation exercise program that was prescribed and adjusted at the 6-week midintervention period based on the assessment results. At baseline, 6-week, and 12-week sessions, participants' physical fitness levels (ie, 6-minute walk test, grip strength test, and 30-second chair stand test) were measured. Physical activity levels, as measured by the International Physical Activity Questionnaire-Short Form (IPAQ-SF); body composition (ie, body mass index, body fat percentage, and muscle mass); biochemical profiles; and quality of life, as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C30, were assessed at baseline and at the end point. At the 6-week midpoint, exercise intensity was individually adjusted. RESULTS: Of the 37 patients, 31 (84%) completed the 12-week intervention. Grip strength improved significantly after 12 weeks of the intervention. The 30-second chair stand test and the 6-minute walk test showed significant improvement from 0 to 6 weeks, from 0 to 12 weeks, and from 6 to 12 weeks. Muscle mass and the IPAQ-SF score increased significantly after 12 weeks of the intervention without biochemical deterioration. CONCLUSIONS: Following 12 weeks of mHealth care, including an individually prescribed rehabilitation exercise program, we saw significant improvements in physical fitness, body composition, and physical activity without any complication or biochemical deterioration among compensated HCC patients who had completed therapy.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Aplicativos Móveis , Telemedicina , Dispositivos Eletrônicos Vestíveis , Carcinoma Hepatocelular/terapia , Feminino , Humanos , Neoplasias Hepáticas/terapia , Masculino , Desempenho Físico Funcional , Qualidade de Vida
9.
Arch Pathol Lab Med ; 144(6): 755-763, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31755778

RESUMO

CONTEXT.­: The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated. OBJECTIVE.­: To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC. DESIGN.­: Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs. RESULTS.­: CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size (P = .001), bile duct margin positivity (P = .001), perineural invasions (P = .04), and higher N categories (P = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, P < .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times (P = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions (P < .001). CONCLUSIONS.­: Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs.


Assuntos
Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Ducto Cístico/patologia , Vesícula Biliar/patologia , Invasividade Neoplásica/patologia , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
10.
PM R ; 12(4): 374-381, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31359596

RESUMO

BACKGROUND: Patients with breast cancer typically experience changes in the properties of muscles around the shoulder. However, there is no appropriate evaluation tool for these changes. OBJECTIVE: The primary objective was to investigate the inter-rater and intra-rater reliability of muscle-related parameters measured by the MyotonPRO, a myotonometer device. The secondary objective was to investigate differences in properties of muscle around the shoulder between the mastectomy side and the other side. DESIGN: Cross-sectional reliability study. SETTING: Outpatient clinic in a tertiary care university-affiliated hospital. PARTICIPANTS: Twenty-two patients with breast cancer who underwent mastectomy. METHODS: Muscle tone, stiffness, and elasticity of the pectoralis major (PM), sternocleidomastoid (SCM), and upper trapezius (UT) were measured using the MyotonPRO. Rater 1 performed two sets of measurements with a time interval of 30 minutes to determine intra-rater reliability. Rater 2 performed measurements during the interval between the two sets of rater 1. Reliability was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. A paired t-test was used to compare muscle properties between the affected and unaffected sides. MAIN OUTCOME MEASUREMENTS: Frequency (tone, Hz), stiffness (N/m), and decrement (elasticity). RESULTS: Intra-rater reliability was excellent (ICC > 0.75, 0.85-0.98) for all parameters of the PM, SCM, and UT in the affected and unaffected upper limbs of patients with breast cancer. Inter-rater reliability was fair to excellent for all parameters except unaffected PM elasticity (ICC = 0.34). There were significant differences in all parameters of the PM between the affected and unaffected sides. There were no significant differences in the parameters of the SCM and UT between the two sides. CONCLUSIONS: Our findings indicate that the MyotonPRO device is a feasible tool to quantify PM, UT, and SCM muscle properties (stiffness, tone, and elasticity) in patients with breast cancer. LEVEL OF EVIDENCE: III.


Assuntos
Neoplasias da Mama , Músculo Esquelético/fisiopatologia , Ombro/fisiopatologia , Neoplasias da Mama/fisiopatologia , Estudos Transversais , Elasticidade , Humanos , Mastectomia , Variações Dependentes do Observador , Reprodutibilidade dos Testes
11.
Cancer Res Treat ; 52(1): 263-276, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31319641

RESUMO

PURPOSE: The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. MATERIALS AND METHODS: Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. RESULTS: Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. CONCLUSION: Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.


Assuntos
Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Criança , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/etiologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/etiologia , Neoplasias Pancreáticas/terapia , Vigilância da População , Prognóstico , República da Coreia , Sensibilidade e Especificidade , Adulto Jovem
12.
Histopathology ; 75(4): 559-567, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31077597

RESUMO

AIMS: Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS: To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P < 0.001), and all NMLEs had low-grade dysplasia. Twelve MCNs with NMLE or MLE were selected for KRAS mutation analysis with droplet digital polymerase chain reaction after laser capture microdissection. All 12 MCNs showed multiple types of KRAS mutation, which were detected in 92% (11/12) of NMLE foci and 89% (8/9) of MLE foci. Predominant NMLE was common in small MCNs with low-grade dysplasia. CONCLUSIONS: Clonal KRAS mutations were observed in both NMLE and MLE, supporting the hypothesis that MCNs with NMLE should be classified as MCNs.


Assuntos
Cistadenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Cistadenocarcinoma Mucinoso/genética , Epitélio/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/genética
13.
J Res Med Sci ; 24: 17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988685

RESUMO

Background: The prevalence of depression and type 2 diabetes mellitus (T2DM) are increasing in the elderly and are reportedly related to each other. We evaluated the relationship between T2DM-related factors and the degree of depression in elderly patients with T2DM based on gender. Materials and Methods: A total of 155 patients with T2DM (56 males and 99 females aged ≥ 65 years) from seven hospitals were included in the study. To assess the status of depressive symptoms, the short form of the Geriatric Depression Scale-Korean version (SGDS-K) was used. We evaluated DM-related factors, such as T2DM duration, hemoglobin A1c (HbA1c) levels, and T2DM complications, as well as other possible factors that could affect depression, such as cognitive function, physical function, education level, and other personal factors. Results: Mean age of the participants was 71.3 years with a mean HbA1c level of 7.6%. Males in the good glycemic control group (HbA1c <7%) showed lower SGDS-K scores compared to those in the poor glycemic control group, and the mean SGDS-K score was higher in the group with a longer duration of DM (M10 years); however, no difference was observed in females. Males and females with microvascular and macrovascular complications tended to have higher SGDS-K scores than participants with no microvascular or macrovascular complications. A multiple linear regression analysis revealed that DM duration and HbA1c level were independently associated with SGDS-K scores in males. Conclusion: Greater depression was associated with poorer glycemic control and a longer duration of DM in elderly males with T2DM.

14.
Pancreas ; 48(3): 400-411, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30747828

RESUMO

OBJECTIVE: Although complete surgical resection is the only curative method for pancreatic cancer, the radial resection margins of pylorus-preserving pancreaticoduodenectomy specimens might be underevaluated. METHODS: KRAS mutation was assessed with droplet digital polymerase chain reaction on cells collected from the radial resection margins of 81 patients, and the results were compared with those of conventional pathologic resection margin (pRM) evaluation. RESULTS: KRAS mutation was detected in 76 patients (94%), and molecular resection margin (mRM) positivity defined by a KRAS mutation rate of 4.19% or greater was observed in 18 patients (22%). Patients with mRM-positive had significantly worse recurrence-free survival (RFS) than those with mRM-negative in entire groups (P = 0.008) and in subgroups without chemotherapy or radiation therapy (all, P < 0.001). When combined pRMs-mRMs were evaluated, patients with combined pRM-mRM-positive (either pRM- or mRM-positive) had significantly worse RFS than those with combined resection margin-negative (both pRM and mRM negative) by univariate (P = 0.002) and multivariate (P = 0.03) analyses. CONCLUSIONS: KRAS mutational analysis with ultrasensitive droplet digital polymerase chain reaction of the radial resection margin in pancreatic cancer patients who underwent pylorus-preserving pancreaticoduodenectomy can provide more accurate information on RFS by using alone or in combination with conventional pRM evaluation, especially in patients without chemotherapy or radiation therapy.


Assuntos
Carcinoma Ductal Pancreático/cirurgia , Margens de Excisão , Mutação , Neoplasias Pancreáticas/cirurgia , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas p21(ras)/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia/métodos , Estudos Retrospectivos
15.
Hum Pathol ; 84: 92-104, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30261192

RESUMO

Identifying the accurate origin of periampullary cancers is important because different origins may trigger different clinicopathological behaviors. The presence of intraepithelial precursor lesions, including high-grade pancreatic intraepithelial neoplasias (PanINs) and/or high-grade biliary intraepithelial neoplasias (BilINs), may be suggestive of the origin of the periampullary carcinoma in challenging cases. To prove the usefulness of high-grade intraepithelial precursor lesions in identifying the origin of ambiguous periampullary cancers, the status and grades of PanINs and BilINs were evaluated in 256 periampullary carcinomas with a well-defined cancer origin as a test set, including 114 pancreatic cancers, 82 distal bile duct cancers, 54 ampullary cancers, and 6 duodenal cancers. One hundred twelve periampullary carcinomas with clinically equivocal epicenter either by radiologic imaging or by endoscopic finding used as a validation set. High-grade PanINs were found more commonly in pancreatic cancers than in distal bile duct, ampullary, and duodenal cancers both in test (P = .002) and validation sets (P < .001). Similarly, high-grade BilINs were identified more frequently in distal bile duct cancers than in ampullary, pancreatic, and duodenal cancers both in test (P < .001) and validation sets (P = .039). High-grade PanINs were found most commonly in pancreatic cancers, whereas high-grade BilINs were seen most frequently in distal bile duct cancers. In addition, both high-grade PanINs and high-grade BilINs are uncommonly noted in ampullary or duodenal cancers. The recognition of high-grade intraepithelial lesions can help identify the primary origin of periampullary cancers, especially when the epicenter of the periampullary cancer is ambiguous.


Assuntos
Ampola Hepatopancreática/patologia , Carcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Pancreas ; 47(10): 1296-1303, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30211805

RESUMO

OBJECTIVES: There is an increasing need for grading with small endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) specimens for the proper diagnosis and therapy selection of patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, our understanding of EUS-FNAB specimen grading is limited compared with surgically resected specimens. METHODS: We retrospectively determined Ki-67 labeling index (LI) of 33 matched EUS-FNAB and surgically resected PanNETs with digital image analyzer. Pairwise grades between the matched biopsy and surgically resected PanNET specimens were compared. RESULTS: The mean Ki-67 LI was higher in surgically resected PanNET specimens (5.5%) than in biopsy specimens (3.2%; P = 0.022). There was moderate agreement between the Ki-67 LI grades when individually evaluated matched biopsy and resected specimen pairs were compared (κ value = 0.62; P < 0.0001). However, discordance was noted in 6 cases (18%), and all of them were either grade 2 or 3 in resected PanNETs. CONCLUSIONS: Although Ki-67 LI grading of EUS-FNAB specimens may be concordant with that of matched surgically resected specimens in a large proportion of the PanNET cases, Ki-67 LI grading of EUS-FNAB specimens should be carefully applied in clinical practice because of the possibility of grading underestimation with grade 2 to 3 PanNET cases.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Antígeno Ki-67/análise , Gradação de Tumores/métodos , Tumores Neuroendócrinos/patologia , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Tumores Neuroendócrinos/metabolismo , Pâncreas/química , Neoplasias Pancreáticas/metabolismo , Reprodutibilidade dos Testes , Estudos Retrospectivos
17.
Virchows Arch ; 472(5): 739-748, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29666945

RESUMO

Well-differentiated pancreatic neuroendocrine neoplasms/tumors (PanNETs) are rare neoplasms with diverse clinical behavior. Biomarker discovery is important for predicting clinical course and prognosis of PanNET patients. Carbonic anhydrase 9 (CA9) and vimentin are hypoxia and epithelial-mesenchymal transition-related proteins of which expression in many carcinomas has been associated with poor prognosis, but their significance in PanNET has yet to be determined. We assessed CA9 and vimentin expression in 164 PanNETs and compared this with clinicopathologic characteristics. CA9 expression was observed in normal islets, while neuroendocrine microadenomas and small (< 1 cm) PanNETs showed loss of CA9 expression. CA9 and vimentin expression was observed in 38 (23%) and 36 (22%) of PanNETs, respectively. CA9 expression was associated with larger size (p = 0.001), higher grade (p < 0.001), higher pT category (p < 0.001), lymph node (p = 0.003) and distant (p = 0.047) metastases, higher AJCC stage (p < 0.001), and lymphovascular (p < 0.001) and perineural (p = 0.002) invasion. PanNET patients with CA9 expression had a shorter recurrence-free survival (5-year survival rate 47%) than those without CA9 expression (76%) by univariate (p = 0.001) but not multivariate analysis. Vimentin expression correlated with CA9 expression (p < 0.001) but not with other clinicopathologic factors. In conclusion, CA9 expression was observed in normal islets, while neuroendocrine microadenomas and small (< 1 cm) PanNETs showed CA9 expression loss. CA9 expression gradually reappeared in larger PanNETs, and this was associated with clinical progression and decreased patient survival by univariate but not multivariate analysis.


Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/análise , Anidrase Carbônica IX/biossíntese , Tumores Neuroendócrinos/enzimologia , Neoplasias Pancreáticas/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Anidrase Carbônica IX/análise , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/mortalidade , Neoplasias Pancreáticas/mortalidade , Modelos de Riscos Proporcionais , Adulto Jovem
18.
Oncotarget ; 9(8): 7867-7881, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29487698

RESUMO

Tumors from 25 patients with pancreatic cancer were used to establish two patient-derived xenograft (PDX) models: orthotopic PDX (PDOX) and heterotopic (subcutaneous) PDX (PDHX). We compared gene expression by immunohistochemistry, single-nucleotide polymorphism (SNP), DNA methylation, and metabolite levels. The 4 cases, of the total of 13 in which simultaneous PDHX & PDOX models were established, were randomly selected. The molecular-genetic characteristics of the patient's tumor were well maintained in the two PDX models. SNP analysis demonstrated that both groups were more than 90% identical to the original patient's tumor, and there was little difference between the two models. DNA methylation of most genes was similar among the two models and the original patients tumor, but some gene sets were hypermethylated the in PDOX model and hypomethylated in the PDHX model. Most of the metabolites had a similar pattern to those of the original patient tumor in both PDX tumor models, but some metabolites were more prominent in the PDOX and PDHX models. This is the first simultaneous molecular-genetic and metabolite comparison of patient tumors and their tumors established in PDOX and PDHX models. The results indicate high fidelity of these critical properties of the patient tumors in the two models.

19.
Surgery ; 163(5): 1071-1079, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29452703

RESUMO

BACKGROUND: The American Joint Committee on Cancer recently proposed the eighth edition of cancer staging system. Validation studies are required to evaluate the prognostic stratification of ampulla of Vater cancer patients. METHODS: In the study, 369 operatively resected patients with ampullary cancers were grouped based on the eighth T (T1a, limited to sphincter of Oddi; T1b, invasion to duodenal submucosa; T2, invasion to duodenal proper muscle; T3a, invasion to pancreas ≤0.5 cm; T3b, invasion to pancreas >0.5 cm; and T4, involvement of celiac axis or superior mesenteric artery) and N (N0, no nodal metastasis; N1, 1-3 nodal metastasis; and N2, ≥4 nodal metastasis) category of ampullary cancer staging. RESULTS: Overall 5-year survival rates for T and N categories were as followed: T1a, 83%; T1b, 71%; T2, 46%; T3a, 48%; T3b, 28.5%, T4, 7% (P< .001); N0, 44.8%; N1, 20%; N2, 4% (P < .001). Pair-wise comparisons demonstrated significant differences between T1a-b (P = .005), T3a-T3b (P = .03), N0-N1 (P < .001), and N1-N2 (P = .007) tumors, but not between T1b-T2 (P = .20), T2-T3a (P = .84), and T3b-T4 (P = .17) lesions. CONCLUSION: The eighth edition T category for ampullary cancer does not stratify patients accurately with regard to prognosis. Modification of the current T category with eliminating subcategories (T1, invasion to duodenal submucosa; T2, invasion to duodenal proper muscle; T3, invasion to pancreas or duodenal subserosa) is a better way for determining prognosis of ampullary cancer. The current N category segregates patient survival well.


Assuntos
Ampola Hepatopancreática/patologia , Carcinoma/patologia , Neoplasias do Ducto Colédoco/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Neoplasias do Ducto Colédoco/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , República da Coreia/epidemiologia , Estudos Retrospectivos
20.
Nanoscale ; 10(6): 3014-3019, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29372742

RESUMO

Recently, InP-based quantum dots (QDs) have received significant attention due to their usefulness in display applications, and the search for good optical properties has led to numerous reports on the testing of reaction variables. However, most researchers have precluded the most important anion precursors in their studies, instead of focusing only on tris(trimethylsilyl)phosphine(P(SiMe3)3, TMS3P) precursors. Due to its vulnerability to moisture, TMS3P is unstable and difficult to handle. In the current study, a new anionic precursor, tris(hexylthio)phosphine(THTP), is introduced for use with InP-based QDs. Owing to its activated phosphine and sulfur atoms, the THTP molecule is a dual anionic precursor for both InP and ZnS QDs. When THTP is reacted with indium and zinc precursors, InPZnS alloy QDs can be fabricated. To observe the synthesis mechanism and probe the intermediate, FAB-mass and 31P-NMR analyses were conducted, resulting in the identification of an intermediate of MW 504. Finally, the surface was coated with a ZnS shell to obtain the emission wavelength from 530 nm to 570 nm and a maximum quantum efficiency of 42% when a ZnI2 precursor was used.

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