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BACKGROUND: BRAF mutation has been recognized as a negative prognostic marker for metastatic colorectal cancer (mCRC), but these data are from common BRAF V600E-mutated mCRC. Combination therapy of BRAF inhibitor and anti-epidermal growth factor receptor (EGFR) antibody has been approved for BRAF V600E-mutated mCRC. However, BRAF non-V600 mutations are rare mutations, and their clinical behavior is not understood. Moreover, the BRAF K601E mutation is extremely rare in mCRC, and there have been no reports on its specific treatment. CASE SUMMARY: Herein, we report the case of a 59-year-old female with super aggressive mCRC with multiple metastases, which extended to whole body including mediastinal to abdominal lymph nodes, bones, pleura, and peritoneum. The companion diagnostics of tumor tissues showed RAS/BRAF wild-type without microsatellite instability. She received chemotherapy with mFOLFOX6 (oxaliplatin plus infusional 5-fluorouracil [5-FU] and leucovorin) plus panitumumab, following FOLFIRI (irinotecan plus infusional 5-FU and leucovorin) plus ramucirumab. For the next regimen selection, a comprehensive genomic profiling panel was performed and revealed a BRAF K601E mutation, which was not covered in the initial companion diagnostics. After disease progression, a combination of encorafenib, binimetinib, and cetuximab was selected as third-line chemotherapy. The serum levels of tumor markers were immediately decreased accompanied by improvements in pleural effusion and ascites. However, the disease progressed again, and best supportive care was done instead. CONCLUSION: This case offers novel insights into the clinical behaviors of BRAF non-V600E-mCRC, potentially advancing personalized therapy for rare and aggressive cases.
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BACKGROUND: Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). METHODS: Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0-III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. RESULTS: Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825-0.956 for stage 0-III CRC and 0.792-0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. CONCLUSIONS: This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity.
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Biomarcadores Tumorais , Neoplasias Colorretais , Dipeptidases , Detecção Precoce de Câncer , Fator Trefoil-1 , Humanos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/urina , Biomarcadores Tumorais/urina , Biomarcadores Tumorais/sangue , Masculino , Detecção Precoce de Câncer/métodos , Feminino , Fator Trefoil-1/urina , Pessoa de Meia-Idade , Idoso , Dipeptidases/urina , Dipeptidases/sangue , Estudos de Casos e Controles , Estadiamento de Neoplasias , Ensaio de Imunoadsorção Enzimática , Adulto , Sensibilidade e Especificidade , Adenoma/diagnóstico , Adenoma/urina , Proteínas Ligadas por GPIRESUMO
Background and Objectives: Despite the fact that biologic drugs have transformed inflammatory bowel disease (IBD) treatment, addressing fibrosis-related strictures remains a research gap. This study explored the roles of cytokines, macrophages, and Krüppel-like factors (KLFs), specifically KLF4, in intestinal fibrosis, as well as the interplay of KLF4 with various gut components. Materials and Methods: This study examined macrophage subtypes, their KLF4 expression, and the effects of KLF4 knockdown on macrophage polarization and cytokine expression using THP-1 monocyte models. Co-culture experiments with stromal myofibroblasts and a conditioned medium from macrophage subtype cultures were conducted to study the role of these cells in intestinal fibrosis. Human-induced pluripotent stem cell-derived small intestinal organoids were used to confirm inflammatory and fibrotic responses in the human small intestinal epithelium. Results: Each macrophage subtype exhibited distinct phenotypes and KLF4 expression. Knockdown of KLF4 induced inflammatory cytokine expression in M0, M2a, and M2c cells. M2b exerted anti-fibrotic effects via interleukin (IL)-10. M0 and M2b cells showed a high migratory capacity toward activated stromal myofibroblasts. M0 cells interacting with activated stromal myofibroblasts transformed into inflammatory macrophages, thereby increasing pro-inflammatory cytokine expression. The expression of IL-36α, linked to fibrosis, was upregulated. Conclusions: This study elucidated the role of KLF4 in macrophage polarization and the intricate interactions between macrophages, stromal myofibroblasts, and cytokines in experimental in vitro models of intestinal fibrosis. The obtained results may suggest the mechanism of fibrosis formation in clinical IBD.
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Fibrose , Fator 4 Semelhante a Kruppel , Macrófagos , Humanos , Citocinas/metabolismo , Doenças Inflamatórias Intestinais , Macrófagos/metabolismo , Monócitos/metabolismo , Fenótipo , Células THP-1RESUMO
INTRODUCTION: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. METHODS: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. RESULTS: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). CONCLUSION: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.
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Ressecção Endoscópica de Mucosa , Inibidores da Bomba de Prótons , Neoplasias Gástricas , Úlcera Gástrica , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Ressecção Endoscópica de Mucosa/métodos , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/etiologia , Úlcera Gástrica/patologia , Úlcera Gástrica/diagnóstico , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Mucosa Gástrica/diagnóstico por imagem , Resultado do Tratamento , Gastroscopia/métodos , Adulto , Invasividade Neoplásica , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer/métodosRESUMO
PURPOSE: Obesity is a risk factor and poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC), but the underlying mechanisms remain unclear. METHODS: PDAC cells and obese visceral adipocytes (O-Ad) derived from mice and humans were used to analyze interactions between the two cell types, and human microvascular endothelial cells were used for angiogenesis assay. A xenograft mouse model with subcutaneously injected PDAC cells was used for animal studies. The relationship between visceral fat and prognosis was analyzed using resected tissues from PDAC patients with and without obesity. RESULTS: Conditioned media (CM) from O-Ad significantly increased PDAC cell growth and migration and angiogenic capacity in both human and mice cells, and blocking osteopontin (OPN) in O-Ad canceled O-Ad-induced effects in both mouse and human cells. In addition, O-Ad directly increased the migratory and tube-forming capacities of endothelial cells, while blocking OPN canceled these effects. O-Ad increased AKT phosphorylation and VEGFA expression in both PDAC and endothelial cells, and OPN inhibition in O-Ad canceled those O-Ad-induced effects. In the xenograft model, PDAC tumor volume was significantly increased in obese mice compared with lean mice, whereas blocking OPN significantly inhibited obesity-accelerated tumor growth. OPN expression in adipose tissues adjacent to human PDAC tumor was significantly higher in obese patients than in non-obese patients. In PDAC patients with obesity, high OPN expression in adipose tissues was significantly associated with poor prognosis. CONCLUSION: Obese adipocytes trigger aggressive transformation in PDAC cells to induce PDAC progression and accelerate angiogenesis via OPN secretion.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Osteopontina/metabolismo , Células Endoteliais/metabolismo , Angiogênese , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Adipócitos/metabolismo , Adipócitos/patologia , Obesidade/complicações , Obesidade/metabolismo , Proliferação de CélulasRESUMO
BACKGROUND AND AIM: Post-endoscopic submucosal dissection coagulation syndrome (PECS) is a recognized complication of colorectal endoscopic submucosal dissection (ESD); however, there is a lack of interventions for preventing PECS. We therefore conducted a prospective study to evaluate the utility of maXium, a novel electrosurgical unit, for preventing PECS. METHODS: This single-center, prospective cohort study prospectively enrolled patients undergoing colorectal ESD. The voltage and power of the electrosurgical units were measured. PECS was defined as a visual analog scale (VAS) ≥ 30 mm, an increase of VAS ≥ 20 mm from baseline, body temperature ≥ 37.5°C, or white blood cell count ≥ 10 000/µL after ESD. PECS was classified into type I (without extra-luminal air) and type II (with peri-luminal air). The primary endpoint was the incidence of PECS. A sample size of 92 patients was required to ensure the upper limit of the 90% CI for the incidence of PECS was less than 15%. RESULTS: At resistances greater than 400 Ω, the maXium unit allowed submucosal dissection with lower power than with the VIO300D unit. Ninety-one patients meeting the inclusion criteria were included in the final study analysis. The incidence of PECS was 16% (90% CI, 10-23%), comprising type I (11%) and type II (5%) PECS. Simple extra-luminal air without PECS was observed in 7% of patients. CONCLUSION: Use of the maXium electrosurgical unit did not reduce the incidence of PECS after colorectal ESD; however, the maXium unit had equivalent performance to a conventional electrosurgical unit used for colorectal ESD.
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Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Eletrocirurgia/efeitos adversos , Estudos Prospectivos , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/etiologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Eletrocoagulação/efeitos adversos , Síndrome , Resultado do TratamentoRESUMO
BACKGROUND: Self-expanding metallic stent (SEMS) and trans-anal colorectal tube (TCT) are alternative treatments to conventional emergency surgery for non-right-sided obstructive colon cancer (NROCC). However, the one with better short- and long-term outcomes remains controversial. Thus, this multicenter case-control study aimed to analyze and compare SEMS and TCT for NROCC. METHODS: Patients with stage II/III NROCC who underwent surgery between January 2010 and December 2019 at either of the eight selected Japanese affiliate hospitals were, retrospectively, reviewed. Baseline characteristics between the SEMS and TCT groups were adjusted by propensity score (PS) matching. RESULTS: Among 239 reviewed patients (SEMS: 76, TCT: 163), 180 were finally included in two well-balanced cohorts through PS: SEMS group (65 patients) and TCT group (115 patients). Technical success, clinical success, morbidity, and short-term mortality were not significantly different between the two groups. SEMS placement achieved significantly higher rates for primary resection/anastomosis without stoma (SEMS: 90.8% vs. TCT: 77.4%, p < 0.001) and laparoscopic surgery (SEMS: 64.6% vs. TCT: 43.5%, p < 0.001) than TCT placement. However, 5-year overall survival (SEMS: 83.7% vs. TCT: 86.4%; p = 0.822) and 5-year relapse-free survival (SEMS: 64.7% vs. TCT: 66.4%; p = 0.854) showed no significant differences between these groups. CONCLUSIONS: Both SEMS and TCT revealed similar long-term outcomes, but SEMS placement was better in achieving primary resection/anastomosis and laparoscopic surgery in patients with stage II/III NROCC.
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Neoplasias do Colo , Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Humanos , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos , Estudos de Casos e Controles , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Recidiva Local de Neoplasia , Neoplasias do Colo/cirurgia , Stents , Resultado do TratamentoRESUMO
The dystrophin-glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as cytidine 5'-diphosphate-glycerol (CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification.
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Distroglicanas , Neoplasias , RNA Nucleotidiltransferases/metabolismo , Distroglicanas/genética , Distroglicanas/metabolismo , Glicerol/metabolismo , Glicerofosfatos , Humanos , Fosfatos/metabolismo , Polissacarídeos/metabolismo , Regulação para CimaRESUMO
Since noninvasive biomarkers as an alternative to invasive colonoscopy to detect colorectal cancer (CRC) are desired, we conducted this study to determine the urinary biomarker consisting of microRNAs (miRNAs). In total, 415 age- and sex-matched participants, including 206 patients with CRC and 209 healthy controls (HCs), were randomly divided into three groups: (1) the discovery cohort (CRC, n = 3; HC, n = 6); (2) the training cohort (140 pairs); and (3) the validation cohort (63 pairs). Among 11 urinary miRNAs with aberrant expressions between the two groups, miR-129-1-3p and miR-566 were significantly independent biomarkers that detect CRC. The panel consisting of two miRNAs could distinguish patients with CRC from HC participants with an area under the curve (AUC) = 0.811 in the training cohort. This panel showed good efficacy with an AUC = 0.868 in the validation cohort. This urinary biomarker combining miR-129-1-3p and miR-566 could detect even stage 0/I CRC effectively with an AUC = 0.845. Moreover, the expression levels of both miR-129-1-3p and miR-566 were significantly higher in primary tumor tissues than in adjacent normal tissue. Our established novel biomarker consisting of urinary miR-129-1-3p and miR-566 enables noninvasive and early detection of CRC.
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BACKGROUND: Molecular features of nonampullary duodenal epithelial tumors (NADETs) remain unclear. AIM: The aim of this study is to determine the association between the genetic features and clinicopathological findings of NADETs. METHODS: In total, 75 NADETs were enrolled in this study, and was performed targeted DNA sequencing of the GNAS, KRAS, TP53, and APC genes. Histological grade was classified as category 3 or category 4/5 according to the Vienna classification, and the immunophenotype was categorized as the gastric phenotype (G type), gastrointestinal phenotype (GI type), or the intestinal phenotype (I type). RESULTS: The prevalence of GNAS and KRAS mutations was significantly higher in the G type than in the GI/I type (GNAS, P = 0.027; KRAS, P = 0.005). In contrast, the frequency of TP53 mutations was significantly higher in the GI/I type than in the G type (P = 0.049). Notably, APC mutations, excluding c.4479 G>A which was synonymous mutation, were more frequently identified in category 4/5 tumors than in category 3 tumors (50% vs. 24.5%; P = 0.039). CONCLUSION: G-type NADETs harbored frequent GNAS and KRAS mutations, whereas TP53 mutations are common in NADETs with intestinal features. APC mutations were significantly associated with high-grade neoplasia and invasive carcinoma.
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Adenocarcinoma , Adenoma , Neoplasias Duodenais , Adenocarcinoma/patologia , Adenoma/patologia , Neoplasias Duodenais/genética , Neoplasias Duodenais/patologia , Humanos , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
Esophageal cancer (EC) including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) generally exhibits poor prognosis; hence, a noninvasive biomarker enabling early detection is necessary. Age- and sex-matched 150 healthy controls (HCs) and 43 patients with ESCC were randomly divided into two groups: 9 individuals in the discovery cohort for microarray analysis and 184 individuals in the training/test cohort with cross-validation for qRT-PCR analysis. Using 152 urine samples (144 HCs and 8 EACs), we validated the urinary miRNA biomarkers for EAC diagnosis. Among eight miRNAs selected in the discovery cohort, urinary levels of five miRNAs (miR-1273f, miR-619-5p, miR-150-3p, miR-4327, and miR-3135b) were significantly higher in the ESCC group than in the HC group, in the training/test cohort. Consistently, these five urinary miRNAs were significantly different between HC and ESCC in both training and test sets. Especially, urinary miR-1273f and miR-619-5p showed excellent values of area under the curve (AUC) ≥ 0.80 for diagnosing stage I ESCC. Similarly, the EAC group had significantly higher urinary levels of these five miRNAs than the HC group, with AUC values of approximately 0.80. The present study established novel urinary miRNA biomarkers that can early detect ESCC and EAC.
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Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas do Esôfago/diagnóstico , MicroRNAs/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/urina , Estudos de Casos e Controles , Linhagem Celular Tumoral , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/urina , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: The natural history and prognosis of superficial nonampullary duodenal epithelial tumors (SNADETs) remain uncertain. We elucidated the relationship between immunophenotype and clinicopathological features. MATERIALS AND METHODS: A total of 98 SNADETs were divided into 3 groups according to immunohistochemical findings: gastric phenotype (G type), gastrointestinal phenotype (GI type), and intestinal phenotype (I type). Cellular dysplasia was divided into low-grade dysplasia and high-grade dysplasia/adenocarcinoma (≥HGD). White opaque substance (WOS) deposition was categorized into diffuse WOS, partial WOS, and no WOS, based on endoscopic findings. RESULTS: Of the 98 SNADETs, 4 lesions (4.1%) were G type, 32 lesions (32.7%) were GI type, and 62 lesions (63.2%) were I type. All G-type SNADETs were located in the oral side of the papilla including the bulb, and the rate of bulbar lesions was significantly higher in the G type than in the GI and I types (p = 0.004). The most frequent type of WOS was no WOS (4/4, 100%) for G type, partial WOS (19/32, 59.4%) for GI type, and diffuse WOS (34/62, 54.8%) for I type (p < 0.001), and loss of intestinal character was significantly correlated with WOS deficiency. GI/I-type SNADETs with partial or no WOS and G-type SNADETs were associated with ≥HGD. Additionally, the frequency of ≥HGD lesion was significantly higher in the CD10-negative group than in the CD10-positive group (57.1 vs. 19.8%, p = 0.043). CONCLUSION: Pathological intestinal character was correlated with the presence of WOS, and CD10 loss was associated with malignant potential of SNADETs.
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Adenocarcinoma , Neoplasias Duodenais , Adenocarcinoma/patologia , Neoplasias Duodenais/patologia , Duodeno/patologia , Humanos , Hiperplasia/patologia , EstômagoRESUMO
Objective Conventional risk scores of peptic ulcer disease (PUD) are based on many parameters, and their application in clinical practice is therefore limited. The aim of this study was to establish simple and reliable criteria for predicting PUD-associated mortality. Methods A total of 499 patients with PUD were divided into 2 groups: the training cohort (n=333) and the validation cohort (n=166). To minimize selection bias due to missing values, we used imputed datasets generated by the multiple imputation method (training-cohort dataset, n=33,300; validation-cohort dataset, n=16,600). Results In the training-cohort dataset, the heart rate-to-systolic blood pressure ratio (HR/SBP) and serum albumin (s-Alb) level were significant independent predictive factors for mortality according to the multivariate analysis [HR/SBP, odds ratio (OR): 1.72; 95% confidence interval (CI), 1.06-2.80, p=0.028; s-Alb, OR: 0.23, 95% CI, 0.11-0.51, p<0.001]. The model comprising HR/SBP and s-Alb was able to detect mortality due to PUD with an area under the curve (AUC) of 0.855. In the validation-cohort dataset, this model also showed good efficacy with an AUC of 0.835. The novel criteria combining HR/SBP and s-Alb developed by a decision tree analysis showed 73.3% sensitivity and 87.6% specificity for predicting mortality in the total-cohort dataset. Our criteria were superior to the Glasgow Blatchford and Rockall scores and similar to the AIMS65 and Progetto Nazionale Emorragia Digestiva scores for predicting mortality. Conclusion The combination of the HR/SBP ratio and s-Alb level is a good predictor of mortality in patients with PUD.
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Hemorragia Gastrointestinal , Úlcera Péptica , Área Sob a Curva , Humanos , Úlcera Péptica/diagnóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND AND AIM: A recent basic study identified that Dicer is contained in exosomes derived from cancer cells and plays crucial roles in microRNA maturation and cancer development. Based on this novel basic concept, we analyzed the usefulness of serum exosomal Dicer as a diagnostic biomarker for gastrointestinal cancers. METHODS: Enrolled participants (691) were categorized into 3 groups: gastric cancer (GC) cohort, 183 patients (90 healthy controls (HCs) and 93 GC patients); esophageal cancer (EC) cohort, 115 patients (90 HCs and 25 EC patients); and colorectal cancer (CRC) cohort, 188 patients (92 HCs and 96 CRC patients) after age- and sex matching using the propensity score. The quality of isolated serum exosomes was validated with an electron microscope, particle size analyzer, and exosome marker, CD63. RESULTS: Serum exosomal Dicer was significantly higher in the GC group than in the HC group (p = 0.004), whereas no significant differences were found in both EC and CRC cohorts. Serum exosomal Dicer was significantly higher in only differentiated gastric adenocarcinoma and not in the undifferentiated type. Moreover, serum exosomal Dicer showed no significant differences regardless of Helicobacter pylori (H. pylori) status. The biomarker panel combining serum exosomal Dicer with H. pylori status distinguished between HC and differentiated GC patients with an area under the curve (AUC) of 0.762. As for early-stage diagnosis, this combination distinguished between HC and stage I differentiated GC with an AUC = 0.758. CONCLUSIONS: Serum exosomal Dicer is a potential noninvasive diagnostic biomarker for early detection of differentiated gastric adenocarcinoma.
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Adenocarcinoma , RNA Helicases DEAD-box , Exossomos , MicroRNAs , Ribonuclease III , Neoplasias Gástricas , Adenocarcinoma/diagnóstico , Biomarcadores Tumorais , RNA Helicases DEAD-box/sangue , Humanos , Ribonuclease III/sangue , Neoplasias Gástricas/diagnósticoRESUMO
OBJECTIVES: Bleeding events related to endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are rare. However, for patients treated with antithrombotic agents, the bleeding risk of EUS-FNA is uncertain. Hence, the aim of this study was to assess the bleeding event rate associated with EUS-FNA in patients receiving antithrombotic treatment. METHODS: A retrospective study was conducted in 742 consecutive patients who underwent EUS-FNA for solid lesions between 2008 and 2015. We compared the bleeding event rates among patients who were not administered antithrombotic agents, those whose agent use was discontinued, those who continued treatment with aspirin or cilostazol, and those who were administered heparin as a replacement. RESULTS: There were 131 patients (17.7 %) treated with antithrombotic agents. Seven experienced bleeding events, and the overall bleeding event rate was 0.9 % (7/742). All bleeding events were intraoperative; there were no postoperative bleeding episodes. Subgroup analysis by antithrombotic agent revealed bleeding event rates of 1.0 % (6/611), 0 % (0/62), 1.6 % (1/61), and 0 % (0/8) for the non-administration, discontinuation of agents, continuation of aspirin or cilostazol, and heparin replacement groups, respectively. Only one severe bleeding event necessitated hemostatic treatment (1/742; 0.1 %); this occurred in a patient in the non-administration group, and there were no severe bleeding events in patients receiving antithrombotic treatment. CONCLUSIONS: The present study found a low incidence of EUS-FNA-related bleeding in patients receiving antithrombotic treatment. The bleeding event rate was low even in patients who underwent EUS-FNA while continuing aspirin or cilostazol.
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Perda Sanguínea Cirúrgica/estatística & dados numéricos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia Pós-Operatória/etiologia , Tromboembolia/prevenção & controle , Ultrassonografia Doppler , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças do Sistema Digestório/diagnóstico , Doenças do Sistema Digestório/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
BACKGROUND/AIMS: Self-expandable metallic stent (SEMS) placement is effective for dysphagia that results from malignant obstruction of the esophagus or gastric cardia; however, stent-related complications may be life-threatening. Thus, the goal of this study was to identify risk factors associated with complications following esophageal stenting. METHODS: Of the 71 patients who underwent SEMS placement for dysphagia as a result of malignant stricture of the esophagus or gastric cardia, 53 patients with squamous cell carcinoma or adenocarcinoma, without previous SEMS placement, without a fistula, and without recurrent tumor after surgery were retrospectively identified. The occurrence of stent-related complications was used as an endpoint. RESULTS: Stent-related complications were identified in 26 patients (49.1%), and major complications occurred in 14 patients (26.4%). The use of an Ultraflex stent (odds ratio [OR], 6.81; 95% confidence interval [CI], 1.54 to 30.00; p=0.011) and prior chemotherapy (OR, 6.13; 95% CI, 1.46 to 25.70; p=0.013) were significantly associated with stent-related complications. Moreover, the use of an Ultraflex stent (OR, 19.60; 95% CI, 2.26 to 170.00; p=0.007) and prior radiation (OR, 25.70; 95% CI, 2.37 to 280.00; p=0.008) significantly increased the risk of major complications. CONCLUSIONS: The use of an Ultraflex stent and prior radiation and/or chemotherapy may represent risk factors for complications following esophageal SEMS placement.
Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Escamosas/cirurgia , Cárdia/cirurgia , Transtornos de Deglutição/cirurgia , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Stents Metálicos Autoexpansíveis , Gastropatias/cirurgia , Adenocarcinoma/complicações , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/complicações , Quimiorradioterapia , Constrição Patológica , Transtornos de Deglutição/etiologia , Fístula Esofágica/epidemiologia , Neoplasias Esofágicas/complicações , Perfuração Esofágica/epidemiologia , Estenose Esofágica/etiologia , Esofagoscopia , Feminino , Febre/epidemiologia , Gastroscopia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Cuidados Paliativos , Pneumonia Aspirativa/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Falha de Prótese , Radioterapia , Estudos Retrospectivos , Gastropatias/etiologiaRESUMO
BACKGROUND AND AIMS: Uncovered self-expandable metal stents (USEMSs) are used to treat unresectable malignant hilar biliary obstructions (MHBOs). However, ingrowth is not prevented, and reintervention is often troublesome. A novel 6-mm threaded fully covered self-expandable metal stent (T-FCSEMS) is available that may mitigate these issues. We aimed to clarify the safety and efficacy of T-FCSEMS placement for MHBO. METHODS: Thirty patients underwent T-FCSEMS placements for MHBOs between 2014 and 2015. T-FCSEMSs were used for initial stenting in 17 patients (initial group) and for reinterventions for USEMS occlusions caused by ingrowth in 13 patients (reintervention group). The technical success rates, times to recurrent biliary obstruction, and the reintervention success rates were evaluated. RESULTS: The technical success rates were 94% (16/17) and 92% (12/13) in the initial group and reintervention group, respectively. Intrahepatic bile duct occlusions caused liver abscesses 8 days and 22 days after T-FCSEMS placements in 2 cases (7%) in the initial group, in which T-FCSEMSs were placed across the intrahepatic bile duct bifurcation. The median times to recurrent biliary obstruction were 210 days in the initial group after bilateral placement and 112 days and 152 days in the reintervention group after bilateral and unilateral placements, respectively. During reintervention, T-FCSEMS removal was successful in all patients in whom it was attempted, and the success rate of endoscopic reintervention was 100% in both groups. CONCLUSIONS: T-FCSEMS placement is a promising option for both initial stenting and reintervention for MHBO. However, we should consider the possibility of intrahepatic bile duct occlusion.
Assuntos
Colestase/cirurgia , Endoscopia do Sistema Digestório , Stents Metálicos Autoexpansíveis , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/complicações , Carcinoma/complicações , Colangiocarcinoma/complicações , Colangiopancreatografia Retrógrada Endoscópica , Colangiopancreatografia por Ressonância Magnética , Colestase/diagnóstico por imagem , Colestase/etiologia , Estudos de Viabilidade , Feminino , Neoplasias da Vesícula Biliar/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS: A barbed puncture needle with a side hole was recently developed to improve sample quality and quantity in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In this study, we retrospectively assessed the usefulness of this puncture needle. METHODS: Factors affecting diagnostic yield, safety, and diagnostic accuracy were investigated in 76 patients who consecutively underwent EUS-FNA for neoplastic lesions at our hospital between January and December 2013. RESULTS: The procedure was successful in all cases; the rates of sample collection and determination of the correct diagnosis were 92.1% and 89.5%, respectively. The mean number of needle passes required for diagnosis was 1.1. Complications included mild intraluminal bleeding in two patients (2.6%). Multivariate analysis revealed that lesion size (≤20 mm) was significantly associated with a decreased chance of determining the correct diagnosis. CONCLUSIONS: Core biopsy needles with a side hole are safe and provide a satisfactory diagnostic yield. However, the side hole may potentially reduce the rate of making the correct diagnosis in small lesions.
Assuntos
Neoplasias do Sistema Digestório/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Agulhas/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Digestório/diagnóstico por imagem , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Agulhas/efeitos adversos , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não ParamétricasRESUMO
BACKGROUND AND AIMS: Recently, endoscopic gallbladder stenting (EGBS) has been performed to prevent recurrences in high-risk surgical patients with cholecystitis. However, evidence regarding the long-term outcomes of EGBS is sparse. We investigated the cholecystitis recurrence rate in high-risk surgical patients with acute calculous cholecystitis and compared the cholecystitis recurrence rates in patients in whom EGBS was performed with those in patients who were observed after percutaneous drainage. METHODS: We studied 64 consecutive high-risk surgical patients with acute calculous cholecystitis who required gallbladder decompression between 2007 and 2014. We divided the patient cohort into patients who underwent observation after percutaneous drainage between 2007 and 2011 (OAPD group) and those who underwent EGBS between 2012 and 2014 (EGBS group), and we compared the groups. RESULTS: The technical success rate of EGBS was 82.9% based on the intention-to-treat analysis. The cholecystitis recurrence rates were 17.2% in the OAPD group and 0% in the EGBS group, a difference that was significant (P = .043). There was also a significant difference between the groups with respect to the time to recurrent cholecystitis, which was determined by using Kaplan-Meier analysis (P = .015). The overall biliary event rates were 24.1% in the OAPD group and 9.1% in the EGBS group, and no significant difference was noted (P = .207). CONCLUSION: EGBS reduced the recurrence of cholecystitis in high-risk surgical patients with calculous cholecystitis. However, stent-related adverse events may occur, and modifications are necessary to reduce these.