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BACKGROUND AND AIMS: EUS-guided hepaticogastrostomy (EUS-HGS) is a rescue procedure when ERCP fails. Peritonitis and recurrent biliary obstruction (RBO) are adverse events (AEs) associated with EUS-HGS. Antegrade stent placement across a malignant distal biliary obstruction (DBO) followed by EUS-HGS (EUS-HGAS) creates 2 biliary drainage routes, potentially reducing peritonitis and prolonging time to RBO (TRBO). We compared the outcomes of the 2 techniques. METHODS: Data of consecutive patients with malignant DBO who underwent attempted EUS-HGS or EUS-HGAS across 5 institutions from January 2014 to December 2020 were retrospectively analyzed. A matched cohort of patients was obtained using 1-to-1 propensity score matching. The primary outcome was TRBO, and secondary outcomes were AEs except for RBO and overall survival. RESULTS: Among 360 patients, 283 (176 and 107 in the HGS and HGAS groups, respectively) were eligible. The matched cohorts included 81 patients in each group. AEs developed in 10 (12.3%) and 15 (18.5%) patients (P = .38) in the HGS and HGAS groups, respectively. RBO occurred in 18 and 2 patients in the HGS and HGAS groups, respectively (P < .001). TRBO was significantly longer in the HGAS group (median, 194 days vs 716 days; hazard ratio, .050; 95% confidence interval, .0066-.37; P < .01). However, no significant differences occurred in overall survival between the groups (median, 97 days vs 112 days; hazard ratio, .97; 95% confidence interval, .66-1.4; P = .88). CONCLUSIONS: EUS-HGAS extended TRBO compared with EUS-HGS, whereas AEs, except for RBO and overall survival, did not differ. The longer TRBO of EUS-HGAS could benefit patients with longer life expectancy.
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Colestasis , Endosonografía , Puntaje de Propensión , Stents , Humanos , Masculino , Femenino , Colestasis/cirugía , Colestasis/etiología , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Estudios de Casos y Controles , Gastrostomía/métodos , Drenaje/métodos , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Ultrasonografía Intervencional , Anciano de 80 o más AñosRESUMEN
BACKGROUND AND AIMS: We compared ERCP using a balloon-assisted endoscope (BE-ERCP) with EUS-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients who had previous R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. The technical success rate was 83.7% versus 83.1% (P = .956), complete stone removal rate was 78.1% versus 67.8% (P = .102), and early adverse event rate was 10.2% versus 18.6% (P = .076) in BE-ERCP and EUS-AG, respectively. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5 ± .8 vs 1.9 ± 1.0 sessions, P = .01), whereas the median total treatment time was longer (90 vs 61.5 minutes, P = .001). Among patients with biliary access, the complete stone removal rate was significantly higher in BE-ERCP (93.3% vs 81.6%, P = .009). Negative predictive factors were CBD diameter ≥15 mm (odds ratio [OR], .41) and an angle of CBD <90 degrees (OR, .39) in BE-ERCP and a stone size ≥10 mm (OR, .07) and an angle of CBD <90 degrees (OR, .07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.
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Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Estudios Retrospectivos , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Gastrectomía , Conducto Colédoco , Endoscopios , Resultado del TratamientoRESUMEN
BACKGROUND: Postoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage. METHODS: Using PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model. RESULTS: From 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40-1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20-1.83, P = 0.37). CONCLUSION: POPFCs can be managed by early EUS-guided drainage without an increase in AEs.
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Endosonografía , Enfermedades Pancreáticas , Humanos , Estudios Retrospectivos , Pancreatectomía , Drenaje , Ultrasonografía Intervencional , Resultado del TratamientoRESUMEN
The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.
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Pancreatic fluid collections (PFCs) typically develop as local complications of acute pancreatitis and complicate the clinical course of patients with acute pancreatitis and potentially fatal clinical outcomes. Interventions are required in cases of symptomatic walled-off necrosis (WON) (matured PFCs with necrosis) and pancreatic pseudocysts (matured PFCs without necrosis). In the management of necrotizing pancreatitis and WON, endoscopic ultrasound-guided transluminal drainage combined with on-demand endoscopic necrosectomy (i.e. the step-up approach) is increasingly used as a less invasive treatment modality compared with a surgical or percutaneous approach. Through the substantial research efforts and development of specific devices and stents (e.g. lumen-apposing metal stents), endoscopic techniques of PFC management have been standardized to some extent. However, there has been no consensus about timing of carrying out each treatment step; for instance, it is uncertain when direct endoscopic necrosectomy should be initiated and finished and when a plastic or metal stent should be removed following clinical treatment success. Despite emerging evidence for the effectiveness of noninterventional supportive treatment (e.g. antibiotics, nutritional support, irrigation of the cavity), there has been only limited data on the timing of starting and stopping the treatment. Large studies are required to optimize the timing of those treatment options and improve clinical outcomes of patients with PFCs. In this review, we summarize the current available evidence on the indications and timing of interventional and supportive treatment modalities for this patient population and discussed clinical unmet needs that should be addressed in future research.
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Pancreatitis Aguda Necrotizante , Humanos , Enfermedad Aguda , Pancreatitis Aguda Necrotizante/cirugía , Pancreatitis Aguda Necrotizante/complicaciones , Endoscopía/métodos , Resultado del Tratamiento , Drenaje/métodos , Stents/efectos adversos , Necrosis/etiología , Estudios RetrospectivosRESUMEN
OBJECTIVES: No comprehensive study has examined short- and long-term adverse outcomes of endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs) including walled-off necrosis (WON) and pseudocysts. METHODS: In a multi-institutional cohort of 357 patients receiving EUS-guided treatment of PFCs (228 with WON and 129 with pseudocysts), we examined PFC type-specific risk factors for procedure-related adverse events (AEs), clinical failure, and recurrence. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the logistic and Cox regression models, respectively, adjusting for potential confounders. RESULTS: Adverse events were observed predominantly in WON, and risk factors were WON extension to the pelvis (OR 2.49; 95% CI 1.00-6.19) and endoscopic necrosectomy (OR 5.15; 95% CI 1.61-16.5). Risk factors for clinical failure in WON treatment included higher Charlson Comorbidity Index (OR for ≥3 vs. ≤2, 2.58; 95% CI 1.05-6.35), extension to the pelvis (OR 3.63; 95% CI 1.57-8.43), nonuse of a lumen-apposing metal stent (OR 2.88; 95% CI 1.10-7.54), and percutaneous drainage (OR 3.73; 95% CI 1.27-10.9). Patients with pseudocysts extending to the paracolic gutter and the need for more than two endoscopic/percutaneous procedures had ORs for clinical failure of 5.28 (95% CI 1.10-25.3) and 5.52 (95% CI 1.61-18.9), respectively. Pseudocysts requiring the multigateway approach were associated with a high risk of recurrence (HR 4.00; 95% CI 1.11-11.6). CONCLUSION: The adverse outcomes at various phases of EUS-guided PFC treatment may be predictable based on clinical parameters. Further research is warranted to optimize treatment strategies for high-risk patients.
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BACKGROUND AND AIM: While encouraging data of endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) using a 22-gauge Franseen needle have been reported, large-scale data of per pass and quantitative analyses are still lacking. METHODS: This was a multicenter prospective study of EUS-FNB using the 22-gauge Franseen needle for a pancreatic solid lesion. Cytological and histological analyses per pass were evaluated and semi-quantitative analyses were performed on core tissue and blood contamination. Primary end-point was diagnostic accuracy per session. Prognostic factors were analyzed for diagnostic accuracy, sensitivity, core tissue, and blood contamination. RESULTS: A total of 629 passes were performed in 244 cases at 14 centers between 2018 and 2019. The median tumor size was 29 mm, and the puncture was transduodenal in 43%. The median pass number was 2. Diagnostic accuracy per session, at a first pass, and per pass were 93%, 90%, and 88%. In 198 cases with pancreatic cancer, diagnostic sensitivity per session, at a first pass, and per pass were 94%, 89%, and 89%. The rates of core tissue score of 4 and blood contamination score of 3 were 50% and 47%. The adverse event rate was 1.6%. In the multivariate analysis, tumor size ≤20 mm (odds ratio [OR] of 0.46, P = 0.03), transduodenal puncture (OR of 0.53, P = 0.04), and suction (OR of 0.16, P = 0.01) were associated with lower diagnostic accuracy. CONCLUSIONS: The EUS-FNB using the 22-gauge Franseen needle for pancreatic solid lesions showed high per pass and overall diagnostic accuracy.
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Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pancreáticas , Humanos , Agujas , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios ProspectivosRESUMEN
BACKGROUND : Endoscopic papillary large balloon dilation (EPLBD) has been increasingly used for the management of large common bile duct (CBD) stones. Although EPLBD is often preceded by endoscopic sphincterotomy (EST), EPLBD alone without EST has been increasingly reported as an alternative to EST for large CBD stones. METHODS : This multicenter randomized trial was conducted at 19 Japanese institutions to compare the efficacy and safety of EPLBD alone versus EST for the removal of large (≥â10âmm) CBD stones. The primary end point was complete stone removal in a single session. The secondary end points included: overall complete stone removal, lithotripsy use, procedure time, adverse events, and cost. RESULTS: 171 patients with large CBD stones were included in the analysis. The rate of single-session complete stone removal was significantly higher in the EPLBD-alone group than in the EST group (90.7â% vs. 78.8â%; Pâ=â0.04). Lithotripsy use was significantly less frequent in the EPLBD group than in the EST group (30.2â% vs. 48.2â%; Pâ=â0.02). The rates of early adverse events were comparable between the two groups: rates of overall adverse events were 9.3â% vs. 9.4â% and of pancreatitis were 4.7â% vs. 5.9â% in the EPLBD and EST groups, respectively. The procedure costs were $1442 vs. $1661 in the EPLBD and EST groups, respectively (Pâ=â0.12). CONCLUSION : EPLBD without EST for the endoscopic treatment of large CBD stones achieved a significantly higher rate of complete stone removal in a single session compared with EST, without increasing adverse events.
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Coledocolitiasis , Cálculos Biliares , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Coledocolitiasis/cirugía , Dilatación , Cálculos Biliares/cirugía , Humanos , Esfinterotomía Endoscópica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Lumen-apposing metal stent is widely used for endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) nowadays but not approved in many countries and might be unsuitable for elective laparoscopic cholecystectomy (LC) because of its large enterocholecysto fistula. A combination of double pigtail plastic stent (DPPS) and naso-cystic tube (NCT) could overcome these problems. The aim of this study was to estimate the efficacy and safety of this method in patients with acute cholecystitis unfit for urgent cholecystectomy both as bridge to surgery and palliation. METHODS: This was a prospective, single-center feasibility study. EUS-GBD was performed with a 7Fr DPPS followed by an NCT placement. NCT was removed after 1 week. LC was performed 2 or 3 months after EUS-GBD in eligible patients. In patients who did not underwent cholecystectomy, DPPS was left in place. RESULTS: Twenty-three patients were enrolled. Both technical and clinical success rates were 96% (22/23). Early adverse events rate was 13% (3/23), including one bile peritonitis, one intraperitoneal abscess, and one melena. LC was attempted in 12 patients, and conversion to open cholecystectomy was required in three (25%). Neither recurrence of cholecystitis nor late adverse event occurred during 6 months of follow up in 10 patients who did not undergo cholecystectomy. CONCLUSION: EUS-GBD with a combination of DPPS and NCT is considered an effective and safe technique both as bridge to surgery and palliation.
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Colecistectomía Laparoscópica/métodos , Colecistitis Aguda/diagnóstico por imagen , Colecistitis Aguda/cirugía , Drenaje/métodos , Vesícula Biliar/cirugía , Cirugía Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Endosonografía/métodos , Estudios de Factibilidad , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
BACKGROUND: In patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial. STUDY: Clinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS. RESULTS: A total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively. CONCLUSIONS: Other than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.
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Colestasis/cirugía , Descompresión Quirúrgica , Tumor de Klatskin , Pancreatitis , Complicaciones Posoperatorias , Stents , Anciano , Colangiografía/métodos , Colestasis/diagnóstico , Colestasis/etiología , Descompresión Quirúrgica/efectos adversos , Descompresión Quirúrgica/instrumentación , Descompresión Quirúrgica/métodos , Análisis de Falla de Equipo/estadística & datos numéricos , Femenino , Humanos , Japón/epidemiología , Tumor de Klatskin/complicaciones , Tumor de Klatskin/patología , Masculino , Estadificación de Neoplasias , Evaluación de Procesos y Resultados en Atención de Salud , Pancreatitis/diagnóstico , Pancreatitis/etiología , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Recurrencia , Estudios Retrospectivos , Stents/efectos adversos , Stents/clasificación , Stents/estadística & datos numéricosRESUMEN
Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Neoplasias Pancreáticas/patología , Neoplasias Peritoneales/secundario , Pronóstico , Tasa de Supervivencia , Tegafur/administración & dosificación , GemcitabinaRESUMEN
BACKGROUND AND AIM: Recurrences after endoscopic treatment of common bile duct stones (CBDS) are common. The aims of this study were to identify risk factors for recurrences of CBDS and to evaluate the effect of interventions for prevention of further recurrences. METHODS: A total of 976 patients who underwent endoscopic treatment of CBDS were retrospectively studied. Risk factors for single and multiple recurrent CBDS were evaluated using a Cox hazard regression model. The incidences of further recurrences were evaluated according to the additional interventions. RESULTS: The mean age was 69.3 years, and 39.3% were female. Endoscopic papillary balloon dilation, endoscopic sphincterotomy, and endoscopic papillary large balloon dilation were performed in 858, 77, and 41 patients, respectively. The rates of one or more recurrence and multiple recurrences of CBDS were 12.4% and 2.7%, respectively. In the multivariate analyses, the significant risk factors were the bile duct size (hazard ratio [HR] 1.07, P = 0.012), gallbladder left in situ with stones (HR 1.91, P = 0.046), and pneumobilia after treatment (HR 2.10, P = 0.047) for single recurrence and the number of stones at the first recurrence (HR 1.16, P = 0.021) for multiple recurrences. In five out of nine cases with multiple recurrences, further recurrence was not observed after additional sphincteroplasty in addition to cholecystectomy. CONCLUSIONS: The incidence of multiple recurrences was not uncommon after the first recurrence of CBDS.
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Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Coledocolitiasis/terapia , Esfinterotomía Endoscópica/efectos adversos , Anciano , Anciano de 80 o más Años , Coledocolitiasis/diagnóstico por imagen , Coledocolitiasis/epidemiología , Dilatación , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Tokio/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Guidewire insertion to a pancreatic duct under wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is associated with a high incidence of post-ERCP pancreatitis (PEP). Pancreatic stent placement followed by WGC (PS-WGC) is considered for these cases to reduce PEP. This study was aimed to examine the effectiveness of PS-WGC compared with repeated WGC. METHODS: The consecutive data of patients without history of ERCP who underwent ERCP for biliary intervention were retrospectively collected from five centers. Patients without guidewire insertion to the pancreatic duct were excluded. Pancreatic stent was immediately placed after guidewire insertion to the pancreatic duct in the PS-WGC group. The association between the method of biliary cannulation (PS-WGC or repeated WGC) and PEP was analyzed using multivariable logistic regression model. RESULTS: A total of 590 patients (183 in the PS-WGC and 407 in the repeated WGC group) were included. PS-WGC decreased PEP (8.7% vs 19%, P = 0.001) and improved its severity (moderate and severe PEP; 2.2% vs 6.4%, P = 0.04) compared with repeated WGC. PS-WGC was associated with reduction of PEP in the multivariable model (Odds ratio 0.31, P < 0.001). The rates of difficult cannulation and overall successful biliary cannulation were not different between the two groups (66% vs 70%, P = 0.39 and 98% vs 96%, P = 0.21 in the PS-WGC and repeated WGC group, respectively). CONCLUSIONS: Pancreatic stent placement followed by WGC reduced PEP in patients with guidewire insertion to the pancreatic duct during WGC for native papilla compared with repeated WGC.
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Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Conductos Pancreáticos , Pancreatitis/etiología , Pancreatitis/prevención & control , Stents , Anciano , Anciano de 80 o más Años , Sistema Biliar , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pancreatitis/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Cholangiocarcinoma is a life-threatening disease with a poor prognosis. Although genome analysis unraveled some genetic mutation profiles in cholangiocarcinoma, it remains unknown whether such genetic abnormalities relate to the effects of anticancer drugs. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma (ICC). Recently, the anticancer effects of BET inhibitors including JQ1 have been shown in various tumors. In the present study, we report that the antigrowth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1. RBE cells harboring IDH1 mutation was more sensitive to JQ1 than HuCCT1 or HuH28 cells with wild-type IDH1. JQ1 induced apoptosis only in RBE cells through the upregulation of proapoptotic genes BAX and BIM. We found that the antigrowth effect was not attributed to downregulation of the MYC gene as a well-known target of JQ1 in various cancer cells. Notably, the forced expression of mutant IDH1 successfully sensitized HuCCT1 cells to JQ1. In addition, AGI-5198, a selective inhibitor of mutant IDH1 partially reversed the decrease in viability after JQ1 treatment and also suppressed the JQ1-induced apoptosis in RBE cells. These data suggest that IDH1 mutation contributed to the growth inhibitory effect of JQ1 in RBE cells. Furthermore, given that the effect of mutant IDH1 was not recapitulated in glioblastoma cells, the enhancement of JQ1 sensitivity by IDH1 mutation seems to be specific for ICC cells. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC.
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Azepinas/farmacología , Neoplasias de los Conductos Biliares/genética , Colangiocarcinoma/genética , Isocitrato Deshidrogenasa/genética , Mutación , Triazoles/farmacología , Proteína 11 Similar a Bcl2/genética , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Regulación hacia Arriba , Proteína X Asociada a bcl-2/genéticaAsunto(s)
Colestasis , Endosonografía , Humanos , Stents , Ultrasonografía Intervencional , Plásticos , DrenajeRESUMEN
BACKGROUND: The necessity of histological analysis is increasing. A 19-gauge histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently been developed and has shown high yields of tissue acquisition and histological diagnosis. AIMS: To compare the histological diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a standard 19-gauge needle (EC19). PATIENTS AND METHODS: Consecutive patients with solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for EUS-FNA with the randomized order of the needles. The primary endpoint was the histological diagnostic accuracy. The secondary endpoints were the feasibility, yield of histological core, cytological and overall diagnostic accuracies, and adverse events. Subgroup analysis was performed for the optimal situation with PC19. RESULTS: Of the 115 patients, 110 underwent EUS-FNA and five were excluded. EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in 26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of presence of a histological core and the histological, cytological, and overall diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593), 83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus 79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric approaches to obtain a histological diagnosis (p = 0.013). Adverse events were observed in four patients. CONCLUSION: Single-pass EUS-FNA with PC19 was feasible and showed significantly higher overall diagnostic accuracy and an increased tendency towards histological diagnostic accuracy, especially with trans-esophageal/gastric FNA.
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Neoplasias Duodenales/patología , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/instrumentación , Neoplasias Esofágicas/patología , Agujas , Neoplasias Gástricas/patología , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy.