RESUMEN
The P2X3 receptor is an attractive target for the treatment of pain and chronic coughing, and thus P2X3 antagonists have been developed as new therapeutic drugs. We previously reported selective P2X3 receptor antagonists by derivatization of hit compound 1. As a result, we identified hit compound 3, the structure of which was similar to hit compound 1. On the basis of SAR studies of hit compound 1, we modified hit compound 3 and compound 42 was identified as having analgesic efficacy by oral administration.
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Antagonistas del Receptor Purinérgico P2X/química , Antagonistas del Receptor Purinérgico P2X/farmacología , Pirazolonas/química , Pirazolonas/farmacología , Receptores Purinérgicos P2X3/metabolismo , Descubrimiento de Drogas , Humanos , Simulación del Acoplamiento Molecular , Pirroles/química , Pirroles/farmacología , Receptores Purinérgicos P2X3/química , Relación Estructura-ActividadRESUMEN
In selecting drug target candidates for pharmaceutical research, the linkage to disease and the tractability of the target are two important factors that can ultimately determine the drug efficacy. Several existing resources can provide gene-disease associations, but determining whether such a list of genes are attractive drug targets often requires further information gathering and analysis. In addition, few resources provide the information required to evaluate the tractability of a target. To address these issues, we have updated TargetMine, a data warehouse for assisting target prioritization, by integrating new data sources for gene-disease associations and enhancing functionalities for target assessment. As a data mining platform that integrates a variety of data sources, including protein structures and chemical compounds, TargetMine now offers a powerful and flexible interface for constructing queries to check genetic evidence, tractability and other relevant features for the candidate genes. We demonstrate these features by using several specific examples.
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Minería de Datos , Desarrollo de Medicamentos , ProteínasRESUMEN
Some P2X3 receptor antagonists have been developed as new therapeutic drugs for pain. We discovered a novel chemotype of P2X3 receptor antagonists with a pyrrolinone skeleton. Because of SAR studies to improve bioavailability of lead compound 2, compound (R)-24 was identified, which showed an analgesic effect against neuropathic pain by oral administration. We constructed a human P2X3 homology model as a template for the zebrafish P2X4 receptor, which agreed with SAR studies of pyrrolinone derivatives.
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Antagonistas del Receptor Purinérgico P2X/farmacología , Pirroles/farmacología , Receptores Purinérgicos P2X3/efectos de los fármacos , Administración Oral , Disponibilidad Biológica , Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento , Humanos , Concentración 50 Inhibidora , Neuralgia/tratamiento farmacológico , Antagonistas del Receptor Purinérgico P2X/administración & dosificación , Antagonistas del Receptor Purinérgico P2X/farmacocinética , Antagonistas del Receptor Purinérgico P2X/uso terapéutico , Relación Estructura-ActividadRESUMEN
Aspergillus flavus is the second most significant pathogenic cause of invasive aspergillosis; however, its emergence risks and mechanisms of voriconazole (VRC) resistance have not yet been elucidated in detail. Here, we demonstrate that repeated exposure of A. flavus to subinhibitory concentrations of VRC in vitro causes the emergence of a VRC-resistant mutant with a novel resistance mechanism. The VRC-resistant mutant shows a MIC of 16 µg/ml for VRC and of 0.5 µg/ml for itraconazole (ITC). Whole-genome sequencing analysis showed that the mutant possesses a point mutation in yap1, which encodes a bZIP transcription factor working as the master regulator of the oxidative stress response, but no mutations in the cyp51 genes. This point mutation in yap1 caused alteration of Leu558 to Trp (Yap1Leu558Trp) in the putative nuclear export sequence in the carboxy-terminal cysteine-rich domain of Yap1. This Yap1Leu558Trp substitution was confirmed as being responsible for the VRC-resistant phenotype, but not for that of ITC, by the revertant to Yap1wild type with homologous gene replacement. Furthermore, Yap1Leu558Trp caused marked upregulation of the atrF ATP-binding cassette transporter, and the deletion of atrF restored susceptibility to VRC in A. flavus These findings provide new insights into VRC resistance mechanisms via a transcriptional factor mutation that is independent of the cyp51 gene mutation in A. flavus.
Asunto(s)
Antifúngicos/farmacología , Aspergillus flavus/genética , Farmacorresistencia Fúngica/genética , Proteínas Fúngicas/genética , Mutación Puntual/genética , Regulación hacia Arriba/genética , Voriconazol/farmacología , Transportadoras de Casetes de Unión a ATP/genética , Aspergillus flavus/efectos de los fármacos , Estrés Oxidativo/genética , Regulación hacia Arriba/efectos de los fármacosRESUMEN
We report the discovery of a novel series of influenza Cap-dependent EndoNuclease (CEN) inhibitors based on the 4-pyridone-carboxylic acid (PYXA) scaffold, which were found from our chelate library. Our SAR research revealed the lipophilic domain to be the key to CEN inhibition. In particular, the position between the chelate and the lipophilic domain in the derivatives was essential for enhancing the potency. Our study, based on virtual modeling, led to the identification of 2y as a potent CEN inhibitor with an IC50 of 5.12nM.
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Antivirales/farmacología , Descubrimiento de Drogas , Endonucleasas/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Orthomyxoviridae/efectos de los fármacos , Piridonas/química , Antivirales/química , Ácidos Carboxílicos/química , Cristalografía por Rayos X , Inhibidores Enzimáticos/química , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND/AIMS: Little is known about the management of occluded multiple metallic stent (MS) deployed in malignant hilar biliary strictures (HBS). The purpose of this study was to evaluate the endoscopic management of occluded multiple MSs deployed in HBS. METHODOLOGY: Fifty-five patients with unresectable biliary tract carcinoma had multiple MSs inserted due to HBS. The endoscopic intervention through the duodenal papilla was performed on 30 cases that had MS occlusion. The procedure success rate, the survival time after the procedure and the number of endoscopic interventions before death were analyzed, retrospectively. RESULTS: The causes of MS obstruction were tissue ingrowth (n=20), sludge (n=7), tumor overgrowth (n=2), and hemobilia (n=1). Endoscopic cleaning or deployment of plastic stents or metallic stents was performed on these patients and was successfully accomplished only via the transpapillary approach. The survival time after MS obstruction was 219 days. The median number of endoscopic interventions before death was 3. The median interval of endoscopic intervention after the first plastic stent occlusion was 84 days. CONCLUSIONS: Our long-term data regarding the endoscopic management of occluded MSs deployed in malignant hilar biliary strictures are acceptable although the patency time of plastic stents deployed after MS occlusion was relatively short.
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Neoplasias de los Conductos Biliares/complicaciones , Conductos Biliares Intrahepáticos , Colangiocarcinoma/complicaciones , Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Colestasis/cirugía , Neoplasias de la Vesícula Biliar/complicaciones , Metales , Complicaciones Posoperatorias/cirugía , Falla de Prótesis , Stents , Anciano , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/mortalidad , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/mortalidad , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/mortalidad , Colestasis/diagnóstico , Colestasis/etiología , Colestasis/mortalidad , Constricción Patológica , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/mortalidad , Diseño de Prótesis , Reoperación , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: The purpose of this study is to evaluate the feasibility of contrast-enhanced ultrasonography (CE-US) to differentiate between benign and malignant intraductal papillary mucinous neoplasms (IPMN). PATIENTS AND METHODS: Contrast-enhanced ultrasonography with a contrast agent was performed on 22 consecutive patients with IPMN suspected of being malignant. This revealed 10 carcinomas, 1 borderline lesion and 11 adenomas. All patients underwent surgery, and the histological diagnosis was confirmed by examination of resected specimens. CE-US was performed using a contrast agent. The detection rates of mural nodules were compared between CE-US and contrast-enhanced computed tomography (CE-CT), and the imaging of mural nodules depicted under CE-US was analyzed. RESULTS: Seventeen of 22 resected specimens (77.3%) had mural nodules. There was no significant difference in the detection rate between CE-US (n=15; 88.2%) and CE-CT (n=12; 70.6%). In 12 (80.0%) of these patients, CE-US revealed small vessels in the mural nodule. The spotty or linear-shaped pattern was detected in 4 patients and the branch-shaped pattern in 8. The branch-shaped pattern lesion was associated with carcinoma. These mural nodules were 10mm or more in height. In the perfusion image phase, cystic walls and mural nodules were also enhanced in all cases. CONCLUSION: The vessel shapes of the mural nodules depicted under CE-US were associated with size and pathological findings. These results suggested that CE-US with a contrast agent is a powerful modality with which to evaluate the malignant potential of IPMN.
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Neoplasias de la Mama/diagnóstico por imagen , Mama/irrigación sanguínea , Carcinoma Ductal Pancreático/diagnóstico por imagen , Neovascularización Patológica/diagnóstico por imagen , Ultrasonografía Mamaria/métodos , Anciano , Neoplasias de la Mama/complicaciones , Carcinoma Ductal Pancreático/complicaciones , Medios de Contraste , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Neovascularización Patológica/etiología , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: This randomized phase II study compared the efficacy and toxicity between 4-week and 3-week schedules of gemcitabine monotherapy in advanced pancreatic cancer. METHODS: Patients with advanced pancreatic cancer were randomly assigned to either a 4-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 3 consecutive weeks every 4 weeks) or a 3-week schedule (gemcitabine at 1000 mg/m² as a 30-min infusion weekly for 2 consecutive weeks every 3 weeks). The primary endpoint was the compliance rate during the first 8 weeks between the two groups. RESULTS: A total of 90 patients were enrolled. The compliance rate during the first 8 weeks was the same (53.3%). For the 4- and 3-week schedules, the tumor response rates were 14.2 and 17.1% (p = 0.92), median progression free survival was 112 and 114 days (p = 0.82), and median overall survival was 206 and 250 days (p = 0.84), respectively. Grade 3-4 neutropenia was the major adverse event in both schedules: 37.7 and 35.5% (p = 0.82). In contrast, thrombocytopenia (platelet count <70000/mm³) was significantly higher for the 4-week schedule: 26.6 and 4.4% (p = 0.008). The mean received dose intensity was equal: 588 and 550 mg/m²/week (p = 0.14). CONCLUSIONS: The 3-week schedule of gemcitabine did not improve the compliance rate during 8 weeks compared with the 4-week schedule, but it attained a comparable efficacy with lower toxicity. Further investigation will be needed to introduce it into daily practice. CLINICAL TRIAL REGISTRATION NUMBER: UMIN ID 974.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neutropenia/inducido químicamente , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
OBJECTIVES: One or more patterns of 6 K-ras mutations are detected in cells from the pancreatic juice of patients with intraductal papillary mucinous neoplasms (IPMNs). We investigated whether these mutations are associated with malignant progression. METHODS: Between January 2002 and December 2007, 53 patients with IPMN were subjected to collection of pure pancreatic juice to evaluate K-ras mutation. According to the histological and radiological findings, the IPMNs were classified into 4 groups: carcinoma group, adenoma group, high-risk group, and low-risk group. We retrospectively investigated the mutation with these groups. RESULTS: In patients with a positive K-ras mutation, a single pattern of K-ras mutation was observed in 80% (8/10) of the carcinoma group, in 71% (5/7) of the adenoma group, in 40% (2/5) of the high-risk group, and in 38% (8/21) of the low-risk group. The rate of a single pattern of K-ras mutation decreased in a stepwise order (P = 0.017). The incidence of a single pattern of K-ras mutation was significantly higher in the patients who received surgical therapy (75%, 12/16) than in those who did not (38%, 10/26; P = 0.033). CONCLUSIONS: The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of IPMNs.
Asunto(s)
Adenocarcinoma Mucinoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/genética , Genes ras , Neoplasias Pancreáticas/genética , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Anciano , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Jugo Pancreático , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVES: The objective of this study was to evaluate the efficacy of a pancreatic stent regarding the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis after aspiration of pure pancreatic juice in patients with intraductal papillary mucinous neoplasms. METHODS: A retrospective study was made to assess the outcome in 121 consecutive patients with intraductal papillary mucinous neoplasms who underwent endoscopic aspiration of pure pancreatic juice for cytologic examination between July 2001 and October 2007. From July 2001 to March 2004, 58 patients did not undergo pancreatic stent insertion (the no-stent [nS] group). The remaining 63 patients did undergo stent insertion (stent [S] group). RESULTS: The overall incidences of post-ERCP pancreatitis was 11 (9.1%). The incidences of post-ERCP pancreatitis in the S and nS groups were 8 (12.7%) and 3 (5.2%; P = 0.21), respectively. In the male patients and the patients with a smaller diameter of the main pancreatic ducts, post-ERCP pancreatitis was seen more frequently in those in the S group (13% and 21%, respectively) than in those in the nS group (0% and 0%, respectively; P = 0.04, 0.03). CONCLUSIONS: The pancreatic stent did not seem to decrease the incidence of post-ERCP pancreatitis in patients with intraductal papillary mucinous neoplasms. Furthermore, the pancreatic stent seems to be potentially detrimental in male patients and in patients with small-diameter main pancreatic ducts.
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Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Papilar/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Neoplasias Pancreáticas/diagnóstico , Pancreatitis/prevención & control , Stents , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Papilar/patología , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Jugo Pancreático/citología , Neoplasias Pancreáticas/patología , Pancreatitis/etiología , Pancreatitis/cirugía , Complicaciones Posoperatorias/patología , Complicaciones Posoperatorias/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND AND STUDY AIMS: Biliary stricture after radiofrequency ablation (RFA) for nodules of hepatocellular carcinoma (HCC) close to major bile ducts sometimes causes septic complications and liver failure. Therefore, it may require interventional drainage for decompression during the follow-up period. The purpose of this study is to clarify the feasibility and safety of bile duct cooling using an endoscopic nasobiliary drainage (ENBD) tube in RFA for HCC close to major bile ducts. PATIENTS AND METHODS: Between August 2003 and July 2007, 14 consecutive patients (14 nodules) undergoing RFA with cooling by an ENBD tube for HCCs close to major bile ducts were enrolled in this study. We infused chilled saline solution via the ENBD tube at 1ml/s to prevent heat damage during RFA. As controls, 11 patients (13 nodules) undergoing RFA without cooling close to major bile ducts between April 2001 and August 2003 were reviewed. The major outcomes for evaluation were biliary complications and the secondary outcome was local tumor recurrence. RESULTS: There were no significant differences in tumor recurrence between the two groups. However, the rate of biliary complications was significantly lower in the cooling group than in the non-cooling group (0% vs. 39%, P=0.02). CONCLUSIONS: Cooling of bile ducts via an ENBD tube can prevent biliary complications induced by RFA of HCC close to major bile ducts without increasing local recurrence. This technique increases indication of RFA in difficult cases.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Colestasis Extrahepática/prevención & control , Drenaje/métodos , Endoscopía/métodos , Hipotermia Inducida/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Anciano , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/diagnóstico por imagen , Colestasis Extrahepática/etiología , Drenaje/instrumentación , Femenino , Humanos , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Radiografía , Resultado del TratamientoRESUMEN
Biliary strictures after living donor liver transplantation (LDLT) with duct-to-duct (D-D) reconstruction are associated with postoperative morbidity and mortality. The aims of this study were to evaluate the long-term outcomes of endoscopic deployment of plastic stents, and to investigate factors associated with the stent deployment failure. Between April 2001 and May 2007, 96 patients received LDLT with D-D reconstruction at Okayama University Hospital. Among them, 41 patients (43%) had anastomotic biliary strictures, and all were referred first for endoscopic retrograde cholangiography (ERC). When deployment was unsuccessful, a percutaneous transhepatic procedure was employed. Successful stent deployment was achieved in 35 out of total 41 patients (85%) by both procedures. Among the 35 patients, 28 had their stents removed as a result of strictures resolution. Eight patients underwent ERC and repeated stent deployment as a result of recurrence of the strictures. Finally, 21 out of 41 (51%) patients with biliary stricture were completely treated by endoscopic therapy during the observation period (median 873 days: range 77-2060). By multivariate analysis, biliary leakage was associated with stent deployment failure. Endoscopic deployment of plastic stents is a first-line therapy for patients with biliary stricture after LDLT.
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Endoscopía/métodos , Trasplante de Hígado/métodos , Adulto , Anciano , Anastomosis Quirúrgica , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestasis/cirugía , Colestasis/terapia , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND & AIMS: For the treatment of unresectable biliary tract carcinoma with hilar biliary stricture, antitumor therapy and biliary stenting should be addressed in terms of prolonged survival with a good quality of life. However, the endoscopic management of malignant hilar biliary strictures is difficult even for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic deployment of multiple JOSTENT SelfX units in patients with hilar biliary strictures treated with or without chemotherapy. METHODS: Between November 2003 and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar biliary strictures by using a partial stent-in-stent procedure was performed on 41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital. Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8). RESULTS: Metallic stent deployment was successfully accomplished in all cases via only endoscopic procedures. During the follow-up period (mean, 210 days), mean patency time was 150 days, and metallic stent obstruction occurred in 15 cases (37%). Although a repeat intervention was required in all metallic stent obstructed cases, the deployment of the second metallic or plastic stent was completed successfully. The remaining 26 cases (63%) required no interventions. The median overall survival period was only 235 days. However, that of the patients receiving chemotherapy was 392 days. CONCLUSIONS: Endoscopic partial stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and safe for the treatment of malignant hilar biliary stricture even in patients receiving chemotherapy.
Asunto(s)
Neoplasias de los Conductos Biliares/complicaciones , Colangiocarcinoma/complicaciones , Colestasis/cirugía , Endoscopía del Sistema Digestivo , Neoplasias de la Vesícula Biliar/complicaciones , Stents , Anciano , Anciano de 80 o más Años , Aleaciones , Antineoplásicos/uso terapéutico , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/mortalidad , Colestasis/etiología , Estudios de Factibilidad , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis/métodos , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla; most cases have been reported in patients with pancreas divisum. It has been suggested that a santorinicele results from a combination of a minor papilla obstruction which prevents the flow of pancreatic juice and a weakness of the duodenal wall where the dorsal pancreatic duct terminates. However, these conditions can occur in patients with invasive ductal cancer in the pancreatic head. We encountered a rare case of a santorinicele with unresectable adenocarcinoma of the pancreatic head in an 81-year-old woman.
Asunto(s)
Adenocarcinoma/complicaciones , Quiste Pancreático/etiología , Conductos Pancreáticos , Neoplasias Pancreáticas/complicaciones , Anciano de 80 o más Años , Colangiopancreatografia Retrógrada Endoscópica , Dilatación Patológica/diagnóstico , Dilatación Patológica/etiología , Femenino , Humanos , Quiste Pancreático/diagnósticoRESUMEN
BACKGROUND: Biliary cannulation is the first step in therapeutic endoscopic retrograde cholangiopancreatography. This study aimed to evaluate unsuccessful cases of biliary cannulation in which the standard procedure was changed to a needle-knife precut papillotomy (NKPP), with particular attention given to postoperative anatomic factors. METHODS: Between October 2002 and February 2006, a total of 501 consecutive patients with an intact duodenal papilla were retrospectively investigated. After biliary cannulation using standard maneuvers was unsuccessful within 20 min, NKPP was performed in 80 cases (16%). The clinical backgrounds for difficult biliary cannulation were compared between patients who had standard maneuvers (n = 421, 84%) and those who underwent NKPP. RESULTS: For 76 difficult cannulation cases (95%), successful cannulation after NKPP was accomplished, and the total success rate reached 99% (497/501). Multivariate analysis indicated that female gender (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.34-3.79), left lobe hypertrophy after hepatectomy (OR, 6.25; 95% CI, 2.52-15.54), history of Billroth I reconstruction after gastrectomy (OR, 7.49; 95% CI, 2.55-22.02), and malignant biliary stricture (OR, 2.31; 95% CI, 1.21- 4.41) were significant risk factors associated with unsuccessful standard procedures used for biliary cannulation. Complications after NKPP were observed in nine cases (11%), all of which were pancreatitis. CONCLUSIONS: Difficult biliary cannulation was strongly associated with postoperative anatomic factors. In these situations, early introduction of NKPP should be recommended if the conventional biliary cannulation promises to be difficult.
Asunto(s)
Ampolla Hepatopancreática/cirugía , Neoplasias de los Conductos Biliares/complicaciones , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colestasis/cirugía , Esfinterotomía Endoscópica/instrumentación , Anciano , Neoplasias de los Conductos Biliares/diagnóstico , Cateterismo/métodos , Colestasis/etiología , Intervalos de Confianza , Estudios de Evaluación como Asunto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias/fisiopatología , Probabilidad , Estudios Retrospectivos , Medición de Riesgo , Esfinterotomía Endoscópica/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ultrasonografía DopplerRESUMEN
A great deal of medical literature describes the efficacy and safety of the prophylactic pancreatic stent in reducing the incidence of post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis. At the moment, no serious complication due to the migration of this stent has been reported. We describe a case with perforation of jejunum induced by the migration of a temporary prophylactic pancreatic stent. This report indicates that we should pay attention to this severe complication when we place a temporary prophylactic pancreatic stent in patients who have peritonitis carcinomatosa or adherence of the intestine irrespective of oral intake.
RESUMEN
BACKGROUND: In view of the recent advancement in endoscopic devices for biliary endoscopic intervention, the expert endoscopist can address complex morbidity. However, endoscopic 3-branched partial stent-in-stent deployment of metallic stents (MS) in patients with malignant hilar biliary stricture is technically demanding. OBJECTIVES: To evaluate the efficacy and safety of endoscopic 3-branched partial stent-in-stent deployment of MS. DESIGN: Case study. SETTING: Gastroenterological Center, Okayama University Hospital. PATIENTS: Nine consecutive patients (mean age 63 years, range 52-84 years, mean follow-up period 5 months) with malignant hilar biliary stricture were enrolled. They had cytologically or histologically proven unresectable biliary-tract carcinoma with hilar biliary stricture type IIIa or IV according to Bismuth's classification. INTERVENTIONS: Endoscopic 3-branched partial stent-in-stent deployment of MS in hilar biliary strictures by using a JOSTENT SelfX stent. MAIN OUTCOME MEASUREMENTS: The success rate of the procedure, stent patency time, reinterventions, and complications. RESULTS: Endoscopic 3-branched partial stent-in-stent deployment was successfully accomplished in all cases. The MS became obstructed in 3 cases (33%), mean 1.5 months, range 1.4 to 2.7 months. However, no MS obstruction occurred in the other 6 patients (67%), mean 11 months, range 4.7 to 16.4 months. In the obstructed cases, the deployment of 2 or 3 tube stents was completed successfully. One case of cholecystitis was observed as a short-term complication. LIMITATION: The small number of cases. CONCLUSIONS: Endoscopic 3-branched partial stent-in-stent deployment of a JOSTENT SelfX stent was effective in selected patients with high-grade malignant hilar biliary stricture.
Asunto(s)
Neoplasias del Sistema Biliar/terapia , Endoscopía del Sistema Digestivo/métodos , Implantación de Prótesis/métodos , Stents , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Biliar/cirugía , Constricción Patológica/cirugía , Constricción Patológica/terapia , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis/instrumentación , Resultado del Tratamiento , Cirugía Asistida por VideoRESUMEN
BACKGROUND: Colonoscopy may be associated with discomfort when performed without sedation. A study was conducted to determine whether instillation of water into the colon at the beginning of the procedure reduces intubation time as well as patient discomfort and pain. METHODS: Colonoscopy was performed in 259 patients by 3 endoscopists-in-training with limited experience. Patients were randomly allocated to 2 groups. In one, a technique was used in which 500 to 1000 mL of water is instilled into the colon by enema at the beginning of the procedure (instillation group, n = 130). In the other, patients underwent a conventional colonoscopy (control group, n = 129). Intubation time was measured and compared between the groups, and subjective discomfort experienced by the patients was measured upon completion of the examination. RESULTS: Success rates for insertion to the cecum were similar, (95.4%, instillation group; 96.1%, control group). Detection rates for any colorectal diseases were not different between the groups (30.0% vs. 32.6%). Mean time to cecal intubation was 10.5 minutes in the instillation group and 16.2 minutes in the control group (p < 0.0001). The proportion of patients who complained of abdominal pain during the procedure was 17.1% in the instillation group and 33.3% in the control group (p < 0.001). CONCLUSIONS: When used by endoscopists-in-training, the water-instillation colonoscopy technique was associated with less discomfort and faster cecal intubation with no decrease in the rate of detection of colorectal diseases.