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1.
Cancers (Basel) ; 13(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578894

RESUMO

This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82. The siRNA-mediated knockdown of MLL2 significantly downregulated global H3K4me3 level and inhibited lung cancer cell proliferation. MLL2 overexpression was found in 14 (33%) of 42 NSCLC patients, and a Cox proportional hazards analysis showed that recurrence-free survival of lung adenocarcinoma patients with MLL2 overexpression was approximately 1.32 (95% CI = 1.08-4.72; p = 0.02) times poorer than in those without it. Metformin showed little effect on DNA methylation and chromatin accessibility at the promoter regions of cell cycle regulatory genes. The present study suggests that metformin reduces H3K4me3 levels at the promoters of positive cell cycle regulatory genes through MLL2 downregulation in lung cancer cells. Additionally, MLL2 may be a potential therapeutic target for reducing the recurrence of lung adenocarcinoma.

2.
Korean J Gastroenterol ; 77(1): 45-49, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33495432

RESUMO

Pancreatic candidiasis can develop in patients with acute pancreatitis, compromised immune responses, or iatrogenic intervention. This paper reports a case of pancreatic candidiasis presenting as a solid pancreatic mass in a patient without the risk factors. A previously healthy 37-year-old man visited the emergency department with left flank pain. Abdominal CT revealed a 5 cm, irregular heterogeneous enhancing mass accompanied by a left adrenal mass. Positron emission tomography-computed tomography and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could not discriminate pancreatic cancer from infectious disease. A laparoscopic exploration was performed for an accurate diagnosis. After distal pancreatectomy with splenectomy and left adrenalectomy, pancreatic candidiasis and adrenal cortical adenoma were diagnosed based on the pathology findings. His condition improved after the treatment with fluconazole. This paper reports a case of primary pancreatic candidiasis mimicking pancreatic cancer in an immunocompetent patient with a review of the relevant literature.

3.
Pancreatology ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33281058

RESUMO

BACKGROUND: Pancreatic neuroendocrine neoplasms (PNENs) show heterogeneous biological behavior, and most small PNENs show indolent features. Consequently, selected cases can be considered for observation only, according to the National Comprehensive Cancer Network guideline, however, supporting clinical evidence is lacking. We investigated the clinical course of small PNENs and their risk factors for malignant potential. METHODS: A total of 158 patients with small pathologically confirmed PNENs ≤2 cm in initial imaging were retrospectively enrolled from 14 institutions. The primary outcome was any metastasis or recurrence event during follow-up. RESULTS: The median age was 57 years (range, 22-82 years), and 86 patients (54%) were female. The median tumor size at initial diagnosis was 13 mm (range, 7-20 mm). PNENs were pathologically confirmed by surgery in 137 patients and by EUS-guided fine needle aspiration biopsy (EUS-FNAB) in 21 patients. Eight patients underwent EUS-FNAB followed by surgical resection. The results of WHO grade were available in 150 patients, and revealed 123 grade 1, 25 grade 2, and 2 neuroendocrine carcinomas. A total of 145 patients (92%) underwent surgical resection, and three patients had regional lymph node metastasis. During the entire follow-up of median 45.6 months, 11 metastases or recurrences (7%) occurred. WHO grade 2 (HR 13.97, 95% CI 2.60-75.03, p = 0.002) was the only predictive factor for malignant potential in multivariable analysis. CONCLUSIONS: WHO grade is responsible for the malignant potential of small PNENs ≤2 cm. Thus, EUS-FNAB could be recommended in order to provide early treatment strategies of small PNENs.

4.
Ann Surg Treat Res ; 99(6): 329-336, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304860

RESUMO

Purpose: Repeating endoscopic retrograde cholangiopancreatography (ERCP) in patients with recurrent common bile duct (CBD) stones is problematic in many ways. Choledochoduodenostomy (CDS) and choledochojejunostomy (CJS) are 2 surgical treatment options for recurrent CBD stones, and each has different advantages and disadvantages. The aim of this study was to compare the 2 surgical options in terms of the recurrence rate of CBD stones after surgical treatment. Methods: This retrospective multicenter study included all patients who underwent surgical treatment due to recurrent CBD stones that were not effectively controlled by medical treatment and repeated ERCP between January 2006 and March 2015. We collected data from chart reviews and medical records. A recurrent CBD stone was defined as a stone found 6 months after the complete removal of a CBD stone by ERCP. Patients who underwent surgery for other reasons were excluded. Results: A total of 27 patients were enrolled in this study. Six patients underwent CDS, and 21 patients underwent CJS for the rescue treatment of recurrent CBD stones. The median follow-up duration was 290 (180-1,975) days in the CDS group and 1,474 (180-6,560) days in the CJS group (P = 0.065). The postoperative complications were similar and tolerable in both groups (intestinal obstruction; 2 of 27, 7.4%; 1 in each group). CBD stones recurred in 4 patients after CDS (4 of 6, 66.7%), and 3 patients after CJS (3 of 21, 14.3%) (P = 0.010). Conclusion: CJS may be a better surgical option than CDS for preventing further stone recurrence in patients with recurrent CBD stones.

5.
Sci Rep ; 10(1): 16251, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33005033

RESUMO

The purpose of this study was to investigate the differences in CT characteristics and disease spread patterns between ROS1-rearranged adenocarcinomas and epidermal growth factor receptor (EGFR)-mutant or anaplastic lymphoma kinase (ALK)-rearranged adenocarcinomas. Patients with stage IIIb/IV adenocarcinoma with ROS1 rearrangement, EGFR mutations, or ALK rearrangement were retrospectively identified. Two radiologists evaluated CT features and disease spread patterns. A multivariable logistic regression model was applied to determine the clinical and CT characteristics that can discriminate between ROS1-rearranged and EGFR-mutant or ALK-rearranged adenocarcinomas. A cohort of 169 patients was identified (ROS1 = 23, EGFR = 120, and ALK = 26). Compared to EGFR-mutant adenocarcinomas, ROS1-rearranged adenocarcinomas were less likely to have air-bronchogram (p = 0.011) and pleural retraction (p = 0.048) and more likely to have pleural effusion (p = 0.025), pericardial metastases (p < 0.001), intrathoracic and extrathoracic nodal metastases (p = 0.047 and 0.023, respectively), and brain metastases (p = 0.017). Following multivariable analysis, age (OR = 1.06; 95% CI: 1.01, 1.12; p = 0.024), pericardial metastases (OR = 10.50; 95% CI: 2.10, 52.60; p = 0.005), and nodal metastases (OR = 8.55; 95% CI: 1.14, 62.52; p = 0.037) were found to be more common in ROS1-rearranged tumors than in non-ROS1-rearranged tumors. ROS1-rearranged adenocarcinomas appeared as solid tumors and were associated with young age, pericardial metastases and advanced nodal metastases relative to tumors with EGFR mutations or ALK rearrangement.

6.
Thorac Cancer ; 11(11): 3205-3212, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33009876

RESUMO

BACKGROUND: Nuclear protein in testis (NUT) carcinoma is a rare tumor associated with NUT rearrangement that can present as poorly differentiated to undifferentiated carcinoma, with or without abrupt squamous differentiation. It is often misdiagnosed as poorly differentiated carcinoma or undifferentiated carcinoma if NUT is not suspected. In this study, we retrospectively analyzed pulmonary NUT carcinoma cases diagnosed with NUT immunohistochemical staining and discuss the differential diagnosis to provide information for this rare and aggressive entity. METHODS: Cases, diagnosed as "NUT carcinoma" in lung pleura and "metastatic NUT carcinoma from the lung" in lymph nodes were diagnosed between 2017 and 2019 at the Samsung Medical Center (SMC). Clinical features such as age, sex, treatment and follow-up period, and pathological reports were obtained by reviewing patients' electronic medical records. RESULTS: A total of 10 NUT carcinoma cases were found in the SMC pathology database. Seven patients were men and six were non-smokers. Tumor cells showed various cellular features such as round, squamoid, and spindle. Some cases had initially been misdiagnosed as spindle cell neoplasm, round cell sarcoma, squamous cell carcinoma and small cell carcinoma. All cases showed diffuse strong nuclear expression of NUT immunohistochemical staining, and some were positive for p63 staining and negative for CD56 staining. CONCLUSIONS: NUT carcinoma is often misdiagnosed because of its various morphologies. It is important to consider NUT as one of the differential diagnoses when encountering lung biopsy with undifferentiated morphology. KEY POINTS: Due to various morphological features, NUT carcinoma can be misdiagnosed It is important to consider NUT carcinoma when diagnosing a poorly differentiated or undifferentiated tumor.

7.
J Clin Med ; 9(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977620

RESUMO

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by ß-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and ß-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16-9.17, p = 0.03). ß-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62-50.91, p = 0.13) to 15.52 (95% CI = 2.94-82.38, p = 0.001) by ß-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed ß-catenin in combination with reduced NME1 expression.

8.
Turk J Gastroenterol ; 31(7): 538-546, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32897228

RESUMO

BACKGROUND/AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is used as a curative method for choledocholithiasis, but little is known about ERCP for patients with end-stage renal disease (ESRD) on hemodialysis (HD). The aim of the current study was to evaluate the efficacy and safety of ERCP for patients with ESRD on HD and to identify the risk factors of ERCP-related bleeding. MATERIALS AND METHODS: The medical records of 61 ESRD patients with choledocholithiasis who underwent ERCP were retrospectively investigated with respect to successful bile duct stone removal and procedure-related adverse events such as pancreatitis, bleeding, and cholangitis. RESULTS: For the study subjects, the overall stone removal success rate was 96.7%, and the overall ERCP-related adverse event rate was 21.3% (pancreatitis, 4.9%; bleeding, 13.1%; cholangitis, 6.6%). Endoscopic sphincterotomy (EST) was found to be associated with hemorrhage (p=0.02), and the occurrence of hemorrhage in patients who underwent EST with or without endoscopic papillary balloon dilation (EPBD) was significantly higher than that in patients who underwent EPBD alone (Odds ratio 1.27, 95% confidence interval 1.075-1.493, p=0.02). CONCLUSION: ERCP for ESRD patients was found to be feasible and safe. However, EST was significantly related to hemorrhagic events. EPBD reduced the risk of hemorrhage and was as effective as EST in terms of stone removal.

9.
Yonsei Med J ; 61(8): 670-678, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734730

RESUMO

PURPOSE: The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. MATERIALS AND METHODS: Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. RESULTS: Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. CONCLUSION: Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Fungos/crescimento & desenvolvimento , Agulhas , Idoso , Feminino , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Micoses/diagnóstico
10.
J Thorac Oncol ; 15(11): 1758-1766, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32652216

RESUMO

INTRODUCTION: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib. METHODS: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. The OS was defined as the time from the diagnosis of LM to death. RESULTS: For the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2-9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31-15.82] versus 9.0 [95% CI: 6.81-11.21], p = 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13-18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34-6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28-0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01-10.39) of those who were never treated with osimertinib but had first- or second-generation EGFR tyrosine kinase inhibitors. CONCLUSIONS: Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status.

11.
Lung Cancer ; 146: 58-65, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32512274

RESUMO

OBJECTIVES: Primary pulmonary salivary gland-type tumors (PSGT) are rare among all types of lung cancer. The purpose of this study was not only to evaluate the clinical outcomes and prognostic factors after treatment, but also to assess the role for bronchoscopic intervention in PSGT. METHODS: We analyzed the medical data of 181 PSGT patients who were treated between 1995 and 2018. Patients were divided into three groups according to the initial treatment, as follows: surgical resection with/without adjuvant therapy including bronchoscopic intervention (surgery group, n = 116); bronchoscopic intervention without surgical resection (bronchoscopic intervention group, n = 51); and other treatments group (n = 14). A multivariable Cox proportional hazard regression analysis was used to identify the independent prognostic factors associated with overall survival (OS) and progression free survival (PFS) after the first treatment. In addition, subgroup analysis was performed according to the clinical stage. RESULTS: Among the 181 patients, 104 (57.5%) patients were diagnosed with adenoid cystic carcinoma (ACC), 71 (39.2%) with mucoepidermoid carcinoma, and 6 (3.3%) with epithelial-myoepithelial carcinoma. In the surgery group, 21 patients underwent bronchoscopic intervention as a bridge therapy before surgery because of respiratory distress. Poor OS was associated with older age, the existence of other malignancy, higher clinical stages, larger tumor size, and non-surgical treatments. Lower PFS was associated with ACC, larger tumor size, and non-surgical treatments. The surgery group had the best OS and PFS among all treatment groups. However, there was no significant difference in the OS between the surgery and bronchoscopic intervention groups (p = 0.66) in patients at high clinical stages. CONCLUSIONS: Surgical resection was the best initial treatment choice. However, bronchoscopic intervention may be useful as the initial treatment in patients at high clinical stage and as a bridge therapy prior to surgery.

12.
J Clin Med ; 9(6)2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32498288

RESUMO

This study aimed to understand the clinicopathological significance of runt-related transcription factor 1 (RUNX1) in non-small cell lung cancer (NSCLC). The methylation and mRNA levels of RUNX1 in NSCLC were determined using the Infinium HumanMethylation450 BeadChip and the HumanHT-12 expression BeadChip. RUNX1 protein levels were analyzed using immunohistochemistry of formalin-fixed paraffin-embedded tissues from 409 NSCLC patients. Three CpGs (cg04228935, cg11498607, and cg05000748) in the CpG island of RUNX1 showed significantly different methylation levels (Bonferroni corrected p < 0.05) between tumor and matched normal tissues obtained from 42 NSCLC patients. Methylation levels of the CpGs in the tumor tissues were inversely related to mRNA levels of RUNX1. A logistic regression model based on cg04228935 showed the best performance in predicting NSCLCs in a test dataset (N = 28) with the area under the receiver operating characteristic (ROC) curve (AUC) of 0.96 (95% confidence interval (CI) = 0.81-0.99). The expression of RUNX1 was reduced in 125 (31%) of 409 patients. Adenocarcinoma patients with reduced RUNX1 expression showed 1.97-fold (95% confidence interval = 1.16-3.44, p = 0.01) higher hazard ratio for death than those without. In conclusion, the present study suggests that abnormal methylation of RUNX1 may be a valuable biomarker for detection of NSCLC regardless of race. And, reduced RUNX1 expression may be a prognostic indicator of poor overall survival in lung adenocarcinoma.

13.
Surg Endosc ; 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32556774

RESUMO

BACKGROUND: The clinical pathway (CP) protocols simplified a systematic process from hospitalization to discharge, and were conducted to achieve standardization of the treatment process as well as improve outcomes. Thus, we investigated the optimal procedure-related hospitalization period following gastric endoscopic submucosal dissection (ESD) by comparing the rate of delayed bleeding (DB) and perforation according to CP protocols. METHODS: We retrospectively enrolled 630 patients who underwent ESD for gastric dysplasia or early gastric cancer (EGC); Group A (368 patients) followed Protocol A for a hospital stay of a single night; Group B (262 patients) followed Protocol B for a hospital stay of two nights. RESULTS: The patient characteristics were comparable between the two groups, except for pathologic diagnosis (42.1% in Group A vs. 32.1% in Group B for EGC). DB occurred in 21 patients, and there was no significant difference in the overall DB rates between Group A (12/368 = 3.3%) and Group B (9/262 = 3.4%) (P = 0.904). The DB rates were 2.5% (8/315) and 7.5% (4/53) in Group A, and 2.7% (6/223) and 7.7% (3/39) in Group B, without and with the use of antiplatelets, respectively, and 33.3% (1/3) in Group A and 50.0% (1/2) in Group B with the use of dual antiplatelets. DB developed at various intervals post-discharge from 2 to 17 days, and was successfully controlled by endoscopic hemostasis in most cases. There were no deaths or surgeries required as a result of uncontrolled DB and no postoperative delayed perforation occurred. CONCLUSIONS: The CP protocols with a one-night hospitalization following gastric ESD decreased the hospital stay and did not influence postoperative complications compared to those with two-night hospitalizations.

14.
Respir Med Case Rep ; 29: 101002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015959

RESUMO

Malignant pulmonary granular cell tumor (GCT) is extremely rare and difficult to distinguish from benign GCT. Most GCTs are neural-type and express S-100. However, a small subset of tumors sub-classified as the non-neural type do not express S-100. We report a case of malignant non-neural-type GCT in the lungs. A 77-year-old woman felt chest discomfort and dyspnea in July 2019. She had never smoked and had no medical history other than hypertension and diabetes mellitus. She was initially evaluated at a local hospital. Flexible bronchoscopy showed total occlusion of the right main bronchus by a mass-like lesion. Biopsy of the mass lesion revealed chronic inflammation. The patient visited for re-evaluation in September 2019. Rigid bronchoscopy showed worsening of the total obstruction of the right main bronchus by a tumor mass, such that the carina was not visible. Additionally, endobronchial nodules were observed on the medial side of left main bronchus. The tumor masses of both main bronchi were removed by bronchoscopic intervention, but the right main bronchus was not opened. Biopsy revealed malignant GCT, favoring the non-neuronal type (S-100-negative). We report an extremely rare case of malignant pulmonary GCT negative for S-100 in immunohistochemistry. In this case, surgical resection was not possible because the tumor was diagnosed at a fairly advanced stage and had spread to involve the contralateral main bronchus. The patient chose to be treated at another hospital and was thereafter lost to follow-up.

15.
PLoS One ; 15(2): e0229299, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32069313

RESUMO

INTRODUCTION: The maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM. MATERIALS AND METHODS: Medical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used. RESULTS: Among the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype. CONCLUSIONS: SUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/terapia , Masculino , Mesotelioma/diagnóstico por imagem , Mesotelioma/terapia , Pessoa de Meia-Idade , Neoplasias Pleurais/diagnóstico por imagem , Neoplasias Pleurais/terapia , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxa de Sobrevida
16.
Hepatobiliary Pancreat Dis Int ; 19(1): 41-50, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31784323

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA. METHODS: Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the profiling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples. RESULTS: Microarray profiling showed that miR-30d-5p and miR-92a-3p were significantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were significantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling pathways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a specificity of 60.5%. CONCLUSIONS: The levels of extracellular miR-30d-5p and miR-92a-3p in bile were significantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.

17.
Korean J Radiol ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33543848

RESUMO

Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.

18.
World J Clin Cases ; 7(20): 3271-3275, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31667178

RESUMO

BACKGROUND: A penetrating injury of a hollow viscus is an obvious indication for an exploratory laparotomy, but is not typically an indication for endoscopic treatment. CASE SUMMARY: A 27-year-old man visited the emergency department with a self-inflicted abdominal stab wound. Injuries to the colon and ileum were detected, but an injury to the second portion of the duodenum was missed. On the day following admission to our institution, the patient became hemodynamically unstable with massive hematochezia, although there was no evidence of bleeding in the Levin tube or Jackson-Pratt drain. We thus performed an upper gastrointestinal endoscopy and discovered a missed duodenal injury that was actively bleeding. An endoscopic band ligation was performed for hemostasis and closure of the perforation. The patient was subsequently discharged without any complications. CONCLUSION: A penetrating injury of the duodenum can be overlooked, so careful abdominal exploration is very important. If a missed duodenal injury is suspected, a cautious endoscopic approach may be helpful.

19.
Int J Mol Sci ; 20(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561631

RESUMO

Programmed cell death ligand 1 (PD-L1) expression is an important biomarker for predicting response to immunotherapy in clinical practice. Hence, identification and characterization of factors that predict high expression of PD-L1 in patients is critical. Various studies have reported the association of PD-L1 expression with driver genetic status in non-small cell cancer; however, the results have been conflicting and inconclusive. We analyzed the relationship between PD-L1 expression and clinicopathological factors including driver genetic alterations in 1000 resected lung cancers using a clinically validated PD-L1 immunohistochemical assay. PD-L1 expression was significantly higher in squamous cell carcinoma (SCC) compared to adenocarcinomas. PD-L1 expression in adenocarcinoma was associated with higher N-stage, solid histologic pattern, EGFR wild type, and ALK positive, but no significant association with the clinicopathological factors in SCC. EGFR mutant adenocarcinomas with distinctive clinicopathologic features, especially solid histologic pattern and higher stage showed higher PD-L1 expression. To the best of our knowledge, this study is the largest to evaluate the association between PD-L1 expression and clinicopathological and molecular features in lung cancer with a highly prevalent EGFR mutation. Therefore, our results are useful to guide the selection of lung cancer, even EGFR-mutated adenocarcinoma patients with PD-L1 expression, for further immunotherapy.


Assuntos
Antígeno B7-H1/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Receptores ErbB , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Adulto Jovem
20.
Lung Cancer ; 134: 7-15, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31319998

RESUMO

OBJECTIVES: Adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transformation (AST) is reported in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer after tyrosine kinase inhibitor (TKI) failure. However, little is known about the underlying genomic changes during the AST process. MATERIALS AND METHODS: We retrospectively reviewed our tissue database collected after first- or second- generation EGFR TKI resistance (n = 263) and identified 3 cases of AST. The additional case was acquired from the osimertinib resistance sample. Deep target sequencing (381 genes) using paired samples from 4 patients with AST after EGFR TKI treatment was performed. The histology of each sample was confirmed by TTF-1 and p63 immunohistochemistry. The patients received first- or second-generation EGFR TKI as an initial treatment. RESULTS: Overall incidence of AST was 1.1% (3/263). Transformed SCC acquired genomic alterations related to the PI3K/AKT/mTOR pathway, in addition to the initial EGFR mutation. In a representative case, two separate sub-clones, with a PTEN nonsense mutation and EGFR p.T790 M mutation, were observed without histologic transformation at the time of gefitinib resistance. After subsequent treatment with osimertinib, SCC transformation was observed with the disappearance of the EGFR p.T790 M mutation and acquired copy number loss in PTEN. Adopting the sub-clonal fraction model elucidates the sub-clonal evolution process of the PTEN mutant sub-clone toward AST under the background of EGFR mutation. The rest of the transformed samples also had acquired genomic alterations in PTEN, LKB1, PIK3CA, or RICTOR, which are related to the PI3K/AKT/mTOR pathway. CONCLUSIONS: Paired genomic analysis from our sample provides early clinical evidence of the ADC to SCC lineage transition that might be provoked by an alteration in the PI3K/AKT/mTOR pathway during EGFR TKI treatment. This finding could potentially broaden the known spectrum of EGFR TKI resistance mechanisms.


Assuntos
Adenocarcinoma de Pulmão/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Genes erbB-1 , Genômica , Mutação , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adulto , Idoso , Alelos , Biópsia , Carcinoma de Células Escamosas/diagnóstico , Evolução Clonal , Feminino , Frequência do Gene , Variação Genética , Genômica/métodos , Mutação em Linhagem Germinativa , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Tomografia Computadorizada por Raios X
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