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1.
Diagnostics (Basel) ; 14(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38535071

RESUMO

This study aimed to develop and validate a simple scoring system to determine the high-risk group for pancreatic cancer (PC) in the asymptomatic general population. The scoring system was developed using data from PC cases and randomly selected non-PC cases undergoing annual medical checkups between 2008 and 2013. The performance of this score was validated for participants with medical checkups between 2014 and 2016. In the development set, 45 PC cases were diagnosed and 450 non-PC cases were identified. Multivariate analysis showed three changes in clinical data from 1 year before diagnosis as independent risk factors: ΔHbA1c ≥ 0.3%, ΔBMI ≤ -0.5, and ΔLDL ≤ -20 mg/dL. A simple scoring system, incorporating variables and abdominal ultrasound findings, was developed. In the validation set, 36 PC cases were diagnosed over a 3-year period from 32,877 participants. The AUROC curve of the scoring system was 0.925 (95%CI 0.877-0.973). The positive score of early-stage PC cases, including Stage 0 and I cases, was significantly higher than that of non-PC cases (80% vs. 6%, p = 0.001). The simple scoring system effectively narrows down high-risk PC cases in the general population and provides a reasonable approach for early detection of PC.

2.
Dig Dis Sci ; 69(3): 969-977, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38300418

RESUMO

OBJECTIVES: In patients with unresectable malignant hilar biliary obstruction (UMHBO), drainage of ≥ 50% liver volume correlates with better clinical outcomes. Accurately measuring the liver volume to be drained by biliary stents is required. We aimed to develop a novel method for calculating the drained liver volume (DLV) using a 3D volume analyzer (3D volumetry), and assess the usefulness for drainage in patients with UMHBO. METHODS: Three-dimensional volumetry comprises the following steps: (1) manual tracing of bile duct using 3D imaging system; (2) 3D reconstruction of bile duct and liver parenchyma; and (3) calculating DLV according to the 3D distribution of bile ducts. Using 3D volumetry, we reviewed data of patients who underwent biliary drainage for UMHBO, calculated the DLV, and determined the association between DLV and biliary drainage outcome. RESULTS: There were 104 eligible cases. The mean DLV was 708 ± 393 ml (53% ± 21%). and 65 patients (63%) underwent drainage of ≥50% liver volume. The clinical success rate was significantly higher in patients with DLV ≥ 50% than in patients with DLV < 50% (89% vs. 28%, P < 0.001). The median time to recurrence of biliary obstruction (TRBO) and survival time were significantly longer in patients with DLV ≥ 50% than in patients with DLV < 50% (TRBO, 292 vs. 119 days, P = 0.03; survival, 285 vs. 65days, P = 0.004, log-rank test, respectively). CONCLUSIONS: Three-dimensional volumetry, a novel method to calculate DLV accurately according to bile duct distribution was useful for drainage in UMHBO patients.


Assuntos
Neoplasias dos Ductos Biliares , Colestase , Humanos , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Colestase/diagnóstico por imagem , Colestase/etiologia , Colestase/cirurgia , Ductos Biliares/patologia , Stents , Drenagem/métodos , Resultado do Tratamento
4.
DEN Open ; 3(1): e169, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36247313

RESUMO

Background: The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ-CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods: We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results: Median PJ-CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ-CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ-CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8-70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non-gastric type than in the gastric type (p < 0.001). The non-gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion: PJ-CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ-CEA predict the non-gastric type, while low PJ-CEA predict the gastric type.

5.
Cancer Sci ; 113(3): 1069-1077, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34962016

RESUMO

Routinely available clinical samples of all stages of pancreatic cancer are used in the present study to elucidate its molecular mechanisms and identify novel therapeutic targets. We evaluated the use of next-generation sequencing (NGS) of endoscopically obtained pancreatic cancer tissues. We enrolled 147 patients who underwent endoscopic ultrasound-guided fine-needle aspiration or endoscopic biopsy. The quantity and quality of the extracted DNA was assessed. Tissue samples were used for NGS of 78 cancer-related genes, from which gene alterations and microsatellite instability (MSI) were extracted. NGS was successful in 141 out of 147 (96%) cases. Gene alterations were detected in 134 out of 141 (91%) samples, among which eight out of 10 samples with a DNA concentration below the detection limit had some type of gene alteration. Targetable genes were detected in 28 (19.9%) cases. MSI and germline mutations in homologous recombination repair associated genes were detected in 5% and 3% of cases, respectively. Cox regression analysis revealed that metastasis (P < .005; hazard ratio [HR], 3.30) was associated with poor prognosis in all pancreatic cancer patients. In addition, fewer than three mutations (P = .03; HR, 2.48) and serum carcinoembryonic antigen levels >5 ng/mL (P < .005; HR, 3.94) were associated with worse prognosis in cases without and with metastasis, respectively. Targeted sequencing of all stages of pancreatic cancer using available samples from real clinical practice could be used to determine the relationship between gene alterations and prognosis to help determine treatment choices.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Taxa de Sobrevida
6.
BMC Cancer ; 21(1): 1245, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798839

RESUMO

BACKGROUND: The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). METHODS: We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. RESULTS: The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p <  0.01). CONCLUSIONS: TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.


Assuntos
Neoplasias da Vesícula Biliar/genética , Genes p53/genética , Mutação , Má Junção Pancreaticobiliar/genética , Adulto , Idoso , Estudos de Casos e Controles , Colecistite/genética , Feminino , Perfilação da Expressão Gênica , Genes do Retinoblastoma , Genes erbB-1 , Genes erbB-2 , Genes ras , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Acúmulo de Mutações , Estudos Retrospectivos , Fatores de Risco
7.
JGH Open ; 5(4): 446-453, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860094

RESUMO

BACKGROUND AND AIM: There are no globally approved, distinguishing criteria enabling the classification of gastric adenomas and intramucosal carcinomas for differential diagnosis of noninvasive neoplasia (NIN). METHODS: Next-generation sequencing of 50 cancer-related genes was undertaken on 68 pathologically diagnosed microdissected gastric neoplasms (25 adenomas, 27 intramucosal carcinomas, and 16 submucosal carcinomas) obtained during endoscopic submucosal dissection. Findings from magnifying endoscopy with narrow-band imaging (M-NBI) of 52 NINs (the 25 adenomas and 27 intramucosal carcinomas) were compared with these data. RESULTS: Among all 68 neoplasms, the most frequently mutated genes were APC (76% in adenoma, 11.1% in intramucosal carcinoma, and 0% in submucosal carcinoma; P < 0.001) and TP53 in intramucosal and submucosal carcinomas (8% in adenoma, 48.1% in intramucosal carcinoma, and 75% in submucosal carcinoma; P < 0.001). Dividing the NIN neoplasms into five groups according to their mutational status (A1: APC mutation, A2: APC + α mutation, B: APC + TP53 mutation, C: TP53 mutation, D: no mutation in either APC or TP53) resulted in almost identical diagnoses by pathology and M-NBI for groups A1 (12/13, 92%), C (12/13, 92%), and D (16/17, 94%) but not for groups A2 (3/7, 43%) or B (0/2, 0%). This finding implies that NINs with the APC + α mutation have carcinoma-like endoscopic features despite most being judged as adenomas by pathology. CONCLUSION: A diagnosis of NINs by pathology or M-NBI in the subset of gastric tumors classified by cancer-related mutations is not completely identical, suggesting the possible additional role of M-NBI in diagnosing NINs. Further studies are needed to confirm this.

8.
JGH Open ; 5(4): 508-516, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860102

RESUMO

BACKGROUND AND AIM: The clinical applicability of digital next-generation sequencing (dNGS), which eliminates polymerase chain reaction (PCR) and sequencing error-derived noise by using molecular barcodes (MBs), has not been fully evaluated. We evaluated the utility of dNGS of cell-free DNA (cfDNA) in liquid biopsies obtained from patients with pancreatic cancer. METHODS: Fifty-eight patients with pancreatic cancer undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) were included. Samples were subjected to sequencing of 50 cancer-related genes using next-generation sequencing (NGS). The results were used as reference gene alterations. NGS of cfDNA from plasma was performed for patients with a mutant allele frequency (MAF) >1% and an absolute mutant number > 10 copies/plasma mL in KRAS or GNAS by digital PCR. Sequence readings with and without MBs were compared with reference to EUS-FNA-derived gene alterations. RESULTS: The concordance rate between dNGS of cfDNA and EUS-FNA-derived gene alterations was higher with than without MBs (p = 0.039), and MAF cut-off values in dNGS could be decreased to 0.2%. dNGS using MBs eliminated PCR and sequencing error by 74% and 68% for TP53 and all genes, respectively. Overall, dNGS detected mutations in KRAS (45%) and TP53 (26%) and copy number alterations in CCND2, CCND3, CDK4, FGFR1, and MYC, which are targets of molecular-targeted drugs. CONCLUSIONS: dNGS of cfDNA using MBs is useful for accurate detection of gene alterations even with low levels of MAFs. These results may be used to inform the development of diagnostics and therapeutics that can improve the prognosis of pancreatic cancer.

9.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809988

RESUMO

New biomarkers are needed to further stratify the risk of malignancy in intraductal papillary mucinous neoplasm (IPMN). Although microRNAs (miRNAs) are expected to be stable biomarkers, they can vary owing to a lack of definite internal controls. To identify universal biomarkers for invasive IPMN, we performed miRNA sequencing using tumor-normal paired samples. A total of 19 resected tissues and 13 pancreatic juice samples from 32 IPMN patients were analyzed for miRNA expression by next-generation sequencing with a two-step normalization of miRNA sequence data. The miRNAs involved in IPMN associated with invasive carcinoma were identified from this tissue analysis and further verified with the pancreatic juice samples. From the tumor-normal paired tissue analysis of the expression levels of 2792 miRNAs, 20 upregulated and 17 downregulated miRNAs were identified. In IPMN associated with invasive carcinoma (INV), miR-10a-5p and miR-221-3p were upregulated and miR-148a-3p was downregulated when compared with noninvasive IPMN. When these findings were further validated with pancreatic juice samples, miR-10a-5p was found to be elevated in INV (p = 0.002). Therefore, three differentially expressed miRNAs were identified in tissues with INV, and the expression of miR-10a-5p was also elevated in pancreatic juice samples with INV. MiR-10a-5p is a promising additional biomarker for invasive IPMN.


Assuntos
Adenocarcinoma Mucinoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/genética , Glicoproteínas de Membrana/genética , Suco Pancreático/metabolismo , Receptores Imunológicos/genética , Adenocarcinoma Mucinoso/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico
10.
Cancer Med ; 10(4): 1264-1274, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33455072

RESUMO

Although comprehensive gene analyses of pancreatic cancer provide new knowledge on molecular mechanisms, the usefulness and possibility of the analyses in routinely available clinical samples remain unclear. We assessed the possibility and utility of target sequencing of endoscopically obtained pancreatic cancer samples. Fifty-eight pancreatic cancer patients who underwent EUS-FNA or endoscopic biopsy were enrolled. The extracted DNA quantity was assessed and used for next-generation sequencing (NGS) of 50 cancer-related genes from which gene mutations, copy number alterations, and microsatellite instability (MSI) were extracted via secondary analysis. A median of 19.2 ng (3.8-228) of DNA was extracted from formalin-fixed paraffin-embedded samples. Gene alterations were detected in 55 of 58 samples (94.8%), including all samples with a DNA concentration below the detection limit (n = 11). Four frequently altered genes were KRAS (83%), TP53 (66%), SMAD4 (26%), and PTEN (17%), and molecular targetable genes were detected in 13 cases (22.4%). Five samples (8.6%) had many mutations and suspected MSI with impaired mismatch repair genes. A Cox regression analysis revealed that metastasis (p < 0.005, hazard ratio [HR] 10.1), serum CEA >5 ng/ml (p = 0.01, HR 2.86), ≤10 detected hotspot mutations (p = 0.03, HR 9.86), and intact Ras signaling (p < 0.005, HR 5.57) were associated with a poor pancreatic cancer prognosis. We performed small, targeted sequencing of pancreatic cancer using available samples from real clinical practice and determined the relationship between gene alterations and prognosis to help determine treatment choices.


Assuntos
Mutação , Neoplasias Pancreáticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biópsia/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia
11.
Int J Mol Sci ; 21(9)2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32392821

RESUMO

We aimed to evaluate a newly developed peroral cholangioscopy (POCS) classification system by comparing classified lesions with histological and genetic findings. We analyzed 30 biopsied specimens from 11 patients with biliary tract cancer (BTC) who underwent POCS. An original classification of POCS findings was made based on the biliary surface's form (F factor, 4 grades) and vessel structure (V-factor, 3 grades). Findings were then compared with those of corresponding biopsy specimens analyzed histologically and by next-generation sequencing to identify somatic mutations. In addition, the histology of postoperative surgical stumps and preoperative POCS findings were compared. Histological malignancy rate in biopsied specimens increased with increasing F- and V-factor scores (F1, 0%; F1, 25%; F3, 50%; F4, 62.5%; p = 0.0015; V1, 0%; V2, 20%; V3, 70%; p < 0.001). Furthermore, we observed a statistically significant increase of the mutant allele frequency of mutated genes with increasing F- and V-factor scores (F factor, p = 0.0050; V-factor, p < 0.001). All surgical stumps were accurately diagnosed using POCS findings. The F-V classification of POCS findings is both histologically and genetically valid and will contribute to the methods of diagnosing the superficial spread of BTC tumors.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Endoscopia do Sistema Digestório/métodos , Mutação , Idoso , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/cirurgia , Biópsia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Sequência de DNA
12.
JGH Open ; 4(1): 75-82, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32055701

RESUMO

BACKGROUND AND AIM: Genetic indicators of endoscopic resection for colorectal carcinoma remain inconclusive. This study analyzed genetic changes in early colorectal tumors that could inform decisions for endoscopic procedures. METHODS: A total of 83 colorectal tumors from 81 patients, including adenoma (n = 7), Tis-T1a (n = 22), T1b (n = 14), and advanced carcinoma (n = 40), were analyzed. Tis tumors (n = 16) and some T1 carcinomas (n = 11) were analyzed as mixed adenomas and carcinomas. Lesions were laser-capture microdissected for DNA extraction, and targeted sequencing of 50 cancer-related genes was performed. Genetic data were then correlated with clinical records, including magnifying endoscopic findings. RESULTS: Numbers of gene alteration rates in TP53 and SMAD4 increased with tumor progression from adenoma to carcinoma. Frequencies of mutant variants in TP53 (P = 0.004) and rates of copy number loss in SMAD4 (P = 0.006) increased in carcinoma components of mixed tumors compared to adenoma components. Moreover, adenoma components of T1b carcinomas had higher TP53 mutation rates than Tis or T1a carcinomas (P = 0.011) and pure adenomas (P = 0.026). Gene alterations in TP53 (P = 0.0055) and SMAD4 (P = 0.0055) increased in cases with irregular surface patterns of magnifying endoscopic findings. CONCLUSIONS: Numbers of copy number variations and TP53 and SMAD4 alterations were related to colorectal tumor progression. TP53 alteration rates in adenoma components were high in T1b carcinomas, warranting complete treatment with en bloc resection. Magnifying endoscopic findings might reflect the genetic status of colorectal tumors.

13.
Nihon Shokakibyo Gakkai Zasshi ; 117(2): 171-177, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32037363

RESUMO

A 63-year-old man developed an infectious pancreatic pseudocyst after acute-on-chronic pancreatitis. The CT and MRI showed the pancreatic pseudocyst communicating with the left branch of the portal vein which now contained cystic fluid. The condition was diagnosed as a pancreatic pseudocyst-portal vein fistula. Because there was no appropriate route through which to drain the pseudocyst, the procedure was performed via the portal vein. The patient's symptoms rapidly improved after the procedure and no recurrence has been observed for three years. Here, we report a rare case of pancreatic pseudocyst-portal vein fistula treated by drainage via the portal vein.


Assuntos
Fístula Pancreática , Pseudocisto Pancreático , Veia Porta , Drenagem , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia
14.
Medicine (Baltimore) ; 98(47): e18039, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764824

RESUMO

The present study is aimed to clarify the utility of magnetic resonance cholangiopancreatography (MRCP) and the additional value of diffusion-weighted imaging (DWI) in diagnosing pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN).This retrospective study involved 38 patients with PDAC concomitant with IPMN and 114 patients (control) who were randomly selected from 320 patients with IPMN without PDAC and were matched with cases for magnetic resonance imaging (MRI) strength (1.5 T/3.0 T). Two radiologists reviewed the 2 MR image sets with relevant clinical information blinded, first MRCP alone and then combined MRI set including DWI. Diagnostic capability and interobserver agreement were assessed by using receiver operating characteristics curve (Az) analysis and weighted κ statistics.Az values for the 2 observers were 0.834 and 0.821 for MRCP alone and 0.964 and 0.926 for the combined MRI (P < .001 and P < .001), respectively. The sensitivity of MRCP alone was 61% (23/38), with both observers failing to diagnose PDACs located at the end of tail or away from the pancreatic duct. Meanwhile, with combined MRI, sensitivity was significantly increased for both observers (61% to 92%, P = .002; 61% to 87%, P = .004). Moreover, the interobserver agreement was higher with combined MRI (κ = 0.85) than MRCP alone (κ = 0.59).MRCP and DWI might be a superior option with a higher diagnostic capability of PDAC concomitant with IPMN than MRCP alone, especially for tumors away from the pancreatic duct.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Colangiopancreatografia por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Pancreas ; 48(8): 1032-1040, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31404021

RESUMO

OBJECTIVES: The aims of this study were to identify genetic characteristics of intraductal papillary mucinous neoplasm (IPMN)-associated pancreatic ductal carcinoma (PDC) and to detect these markers using pancreatic juice. METHODS: From 76 cases, 102 tissues were obtained: 29 cases were noninvasive IPMN, 18 were PDC derived from IPMN (D-PDC; noninvasive part, n = 16; invasive part, n = 18), and 29 were PDC concomitant with IPMN (C-PDC; IPMN part, n = 10; PDC part, n = 29). Moreover, pancreatic juice samples from 28 cases were obtained (noninvasive IPMN, n = 13; D-PDC, n = 7; C-PDC, n = 8). Fifty-one cancer-related genes were analyzed by next-generation sequencing. RESULTS: TP53 mutation rates in D-PDC, C-PDC, and noninvasive IPMN were 67%, 66%, and 10%, respectively. Moreover, KRAS mutational patterns between 2 simultaneous tumors differed in 1 (6.3%) of the 16 D-PDC cases and in 8 (80%) of the 10 C-PDC cases (P = 0.0006). TP53 or multiple KRAS mutations were detected using pancreatic juice more frequently in C-PDC cases than in noninvasive IPMN cases (75% and 23%, respectively, P = 0.03). CONCLUSIONS: Multiple KRAS mutations along with TP53 mutation are genetic markers for C-PDC, which could be detected using pancreatic juice preoperatively.


Assuntos
Adenocarcinoma Mucinoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/genética , Mutação , Suco Pancreático/metabolismo , Neoplasias Pancreáticas/genética , Adenocarcinoma Mucinoso/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Papilar/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
16.
J Gastroenterol ; 54(11): 1029-1037, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31111221

RESUMO

BACKGROUND: The present study aimed to determine the ability of diagnosing malignancy and predicting malignant transformation in patients with IPMN using carcinoembryonic antigen (CEA) level in the pancreatic juice. METHODS: We enrolled patients with IPMN who underwent endoscopic retrograde pancreatography (ERP) between 2002 and 2018. We examined the ability of diagnosing malignancy in 63 patients who underwent surgery (surgical group). Furthermore, we examined the value of predicting malignant transformation in 52 patients who underwent follow-up for over 1 year after ERP (follow-up group). RESULTS: In the surgical group, the overall sensitivity and specificity of CEA level (≥ 97 ng/ml) in the pancreatic juice for diagnosing malignancy were 45% and 100%, respectively. The specificity was excellent for all IPMN types; however, the sensitivity was highest in main duct type, followed by mixed type and branch duct type. In the follow-up group, malignant transformation was observed in four patients (7.7%) during the follow-up, and the median time until malignant transformation was 58 months. High CEA level in the pancreatic juice demonstrated a statistically significant difference in multivariate analysis and was found to be an independent predictor of malignant transformation (hazard ratio 17; P = 0.02). The cumulative malignant transformation rate was significantly higher in the high CEA group than that in the low CEA group (5-year cumulative malignant transformation rates, 69% vs. 0%, P < 0.001). CONCLUSIONS: Carcinoembryonic antigen level in the pancreatic juice is useful not only in diagnosing malignancy but also in predicting future malignant transformations in IPMN patients receiving follow-up.


Assuntos
Antígeno Carcinoembrionário/metabolismo , Neoplasias Intraductais Pancreáticas/patologia , Suco Pancreático/química , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Intraductais Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
17.
World J Clin Cases ; 7(1): 10-18, 2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30637248

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy has been a major challenge to gastrointestinal endoscopists with low success rates for reaching the target site as well as high complication rates. The knowledge of ERCP-related risk factors is important for reducing unexpected complications. AIM: To identify ERCP-related risk factors for perforation in patients with surgically altered anatomy. METHODS: The medical records of 187 patients with surgically altered anatomy who underwent ERCP at our institution between April 2009 and December 2017 were retrospectively reviewed. An analysis of patient data, including age, sex, type of reconstruction, cause of surgery, aim of ERCP, success rate of reaching target site, success rate of procedure, adverse events, type of scope, time to reach the target site, and duration of procedure, was performed. In patients with Billroth-II reconstruction, additional potential risk factors were the shape of the inserted scope and whether the anastomosis was antecolic or retrocolic. RESULTS: All patients (n = 187) had surgical anatomy, such as Billroth-I (n = 22), Billroth-II (n = 33), Roux-en-Y (n = 54), Child, or Whipple reconstruction (n = 75). ERCP was performed for biliary drainage in 43 cases (23%), stone removal in 29 cases (16%), and stricture dilation of anastomosis in 59 cases (32%). The scope was unable to reach the target site in 17 cases (9%), and an aimed procedure could not be accomplished in 54 cases (29%). Adverse events were pancreatitis (3%), hyperamylasemia (10%), cholangitis (6%), cholestasis (4%), excessive sedation (1%), perforation (2%), and others (3%). Perforation occurred in three cases, all of which were in patients with Billroth-II reconstruction; in these patients, further analysis revealed loop-shaped insertion of the scope to be a significant risk for perforation (P = 0.01). CONCLUSION: Risk factors for perforation during ERCP in patients with surgically altered anatomy were Billroth-II reconstruction and looping of the scope during Billroth-II procedure.

18.
BMC Gastroenterol ; 17(1): 105, 2017 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-29020933

RESUMO

BACKGROUND: Self-expandable metal stents (SEMSs) are widely used for malignant biliary obstructions. Nitinol-covered SEMSs have been developed to improve stent patency. Currently, SEMSs may be uncovered, partially covered, or fully covered; however, there is no consensus on the best stent type for the management of malignant distal biliary obstruction (MDBO). METHODS: Patients with unresectable MDBO receiving SEMS (Wallflex™) were retrospectively analyzed. Time to recurrent biliary obstruction (TRBO) and survival time were compared among the three types of SEMSs. Univariate and multivariate analyses were performed to identify risk factors for stent dysfunction. RESULTS: In total, 101 patients received SEMSs for unresectable MDBO (44 uncovered, 28 partially covered, and 29 fully covered SEMSs). Median survival time was 200, 168, and 276 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. There were no differences in survival among the three groups. Median TRBO was 199, 444, and 194 days in the uncovered, partially covered, and fully covered SEMSs groups, respectively. Partially covered SEMSs had longer TRBO than uncovered (p = 0.013) and fully covered (p = 0.010) SEMSs. Tumor ingrowth occurred only with uncovered SEMSs and stent migration occurred only with fully covered SEMSs. Multivariate analyses confirmed that partially covered SEMSs have lower risk of dysfunction. CONCLUSIONS: Partially covered SEMSs with a proximal uncovered flared end have longer patency than uncovered and fully covered SEMSs by preventing tumor ingrowth and stent migration.


Assuntos
Colestase/cirurgia , Desenho de Prótese , Falha de Prótese , Stents Metálicos Autoexpansíveis , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/complicações , Neoplasias do Sistema Biliar/mortalidade , Colestase/etiologia , Colestase/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/mortalidade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Stents Metálicos Autoexpansíveis/efeitos adversos , Análise de Sobrevida , Fatores de Tempo
19.
World J Gastroenterol ; 23(18): 3295-3300, 2017 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-28566889

RESUMO

AIM: To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP). METHODS: Thirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 cases. RESULTS: The sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid administration. CONCLUSION: SG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.


Assuntos
Doenças Autoimunes/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , Pancreatite/diagnóstico por imagem , Sialadenite/diagnóstico por imagem , Glândula Submandibular/diagnóstico por imagem , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Retrospectivos , Glândula Submandibular/fisiopatologia
20.
Hepatogastroenterology ; 62(140): 821-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26902009

RESUMO

BACKGROUND/AIMS: Patients with ulcerative colitis suffer from long term impairment of quality of life, especially when subjected to repeated hospitalization. We aimed to identify factors that may predict future hospitalization. METHODOLOGY: We followed 139 consecutive patients with ulcerative colitis for average of 11.2 years (2.8 to 49.5 years) from the onset. Clinical and endoscopic stagings were determined by Japanese staging system, the extent of colitis by Montreal classification and endoscopic grading by Matts' grade. RESULTS: Overall hospitalization rate was 37% at 5 years, 47% at 10 years and 60% at 20 years from the onset. Of 5 parameters including demographic and staging scores, univariate analysis revealed clinical severity at onset (p = 0.003), total colonoscopic findings on severity (Matts' grade, p = 0.003), and total colonoscopic findings on sites of abnormality (p = 0.012) were significantly correlated with hospitalization. By multivariate analysis, total colonoscopic findings on sites of abnormality was the only baseline character significantly related to the need of hospitalization (p = 0.0007). In fact, 5/10/20 years hospitalization rates were only 18/26/33 percent for proctitis type, whereas those were 61/72/90 for total colitis type. CONCLUSIONS: The total colonoscopic finding on sites of abnormality at the onset is the only predictdr of hospitalization in patients with ulcerative colitis.


Assuntos
Colite Ulcerativa/patologia , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Colonoscopia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
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