RESUMEN
In the management of ulcerative colitis (UC), colonoscopy (CS) is considered essential for diagnosis;however, its invasiveness poses a challenge. Conversely, recent advancements in ultrasound diagnostic devices have improved imaging quality for the digestive tract, rendering them valuable in UC management. Therefore, this study aimed to elucidate the correlation between abdominal ultrasonography (AUS) and CS in assessing UC activity. The indices adopted for UC evaluation using AUS were as follows:1) bowel wall stratification, 2) bowel wall thickness, 3) bowel wall flow at power Doppler, 4) presence of increased brightness of inflammatory fat, and 5) presence of mesenteric lymph node swelling greater than 5mm. Subsequently, we developed a new AUS index for UC, termed the UCUS score, which comprises the aforementioned five indices. Finally, we compared the UCUS score with representative endoscopic indices, the Mayo endoscopic sub-score, and the Ulcerative Colitis Endoscopic Index of Severity. The results demonstrated that our proposed UCUS score better reflected disease activity than individual items assessed separately. ROC curve analysis revealed a UCUS score cutoff of 3 points. Therefore, a UCUS score of ≥3 points indicates the need for further examination with CS. Conversely, a score below 3 points suggests low disease activity, and in situations when evaluating treatment effectiveness, AUS could potentially substitute for CS. We believe that the UCUS score is an important source of information to understand the patient's condition and to motivate the patient to undergo endoscopy.
Asunto(s)
Colitis Ulcerosa , Ultrasonografía , Colitis Ulcerosa/diagnóstico por imagen , Humanos , Abdomen/diagnóstico por imagen , Índice de Severidad de la EnfermedadRESUMEN
Here, we report on the increase of the quality-factors of photonic crystal nanocavities fabricated by a CMOS-compatible process. We fabricated nanocavities with the same cavity design but used either a binary photomask or a phase-shift photomask in the photolithography step to assess the impact of the photomask-type on the fabrication accuracy of the air holes. We characterized 62 cavities using time-resolved measurements and the best cavity had a quality-factor of 6.65 × 106. All cavities exhibited a quality-factor larger than 2 million and the overall average was 3.25 × 106. While the estimated magnitude of the scattering loss due to the air hole variations in the 33 cavities fabricated with the phase-shift photomask was slightly lower than that in the 29 cavities fabricated with binary photomask, the phase-shift photomask did not provide a significant improvement in the fabrication accuracy. On average, the scattering loss in these samples is more than 3 times larger than that of nanocavities fabricated using electron-beam lithography, which indicates room for further improvement.
RESUMEN
OBJECTIVE: IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. DESIGN: We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). RESULTS: Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. CONCLUSIONS: IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice.
Asunto(s)
Enfermedades Autoinmunes , Inmunoglobulina G , Páncreas , Pancreatitis , Glándulas Salivales , Animales , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Técnicas de Cultivo de Célula , Modelos Animales de Enfermedad , Humanos , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/sangre , Masculino , Ratones , Páncreas/inmunología , Páncreas/patología , Pancreatitis/inmunología , Pancreatitis/patología , Glándulas Salivales/inmunología , Glándulas Salivales/patologíaRESUMEN
OBJECTIVES: Although simultaneous occurrences of autoimmune pancreatitis (AIP) and cancer are occasionally observed, it remains largely unknown whether cancer and AIP occur independently or these disorders are interrelated. The aim of this study was to examine the relationship between AIP and cancer. METHODS: We conducted a multicenter, retrospective cohort study. One hundred and eight patients who met the Asian diagnostic criteria for AIP were included in the study. We calculated the proportion, standardized incidence ratio (SIR), relative risk, and time course of cancer development in patients with AIP. We also analyzed the clinicopathological characteristics of AIP patients with cancer in comparison with those without cancer. RESULTS: Of the 108 AIP patients, 18 cancers were found in 15 patients (13.9%) during the median follow-up period of 3.3 years. The SIR of cancer was 2.7 (95% confidence interval (CI) 1.4-3.9), which was stratified into the first year (6.1 (95% CI 2.3-9.9)) and subsequent years (1.5 (95% CI 0.3-2.8)) after AIP diagnosis. Relative risk of cancer among AIP patients at the time of AIP diagnosis was 4.9 (95% CI 1.7-14.9). In six of eight patients whose cancer lesions could be assessed before corticosteroid therapy for AIP, abundant IgG4-positive plasma cell infiltration was observed in the cancer stroma. These six patients experienced no AIP relapse after successful cancer treatment. CONCLUSIONS: Patients with AIP are at high risk of having various cancers. The highest risk for cancer in the first year after AIP diagnosis and absence of AIP relapse after successful treatment of the coexisting cancers suggest that AIP may develop as a paraneoplastic syndrome in some patients.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Neoplasias/etiología , Pancreatitis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/inmunología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulina G/sangre , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Pancreatitis/diagnóstico , Pancreatitis/inmunología , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/etiología , Factores de Tiempo , Adulto JovenRESUMEN
We investigate nanocavities at the surface of three-dimensional (3D) photonic crystals, where the polarization-independent surface-mode gap can be utilized. We consider the formation of various nanocavities by introducing artificial defects utilizing the 3D structures around the surface and discuss the possibilities for increasing the Q-factors of the surface nanocavities with TE-like polarization based on the advanced designs of donor-type defects. We also introduce the design of acceptor-type defects and show that TM-like nanocavities are obtained. We then fabricate the designed nanocavities and examine their resonant characteristics; we successfully demonstrate TE-like nanocavities with Q-factors of ~40,000, which is four-times higher than previous surface cavities and as high as that of the cavities embedded inside 3D photonic crystals. TM-like nanocavities with Q-factors of ~22,000 are also demonstrated for the first time.
Asunto(s)
Nanopartículas/química , Nanopartículas/ultraestructura , Nanotecnología/instrumentación , Resonancia por Plasmón de Superficie/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Fotones , Propiedades de SuperficieRESUMEN
We have investigated the photonic modes at the surface of three-dimensional photonic crystals fabricated using a top-down approach involving two-step etching at angles of ± 45°. Numerical simulations revealed the properties of these surface modes, including their polarization characteristics and dependence on the surface structure. The formation of surface modes was experimentally demonstrated using an evanescent-coupling method and agreed well with the simulations.
Asunto(s)
Materiales Manufacturados , Modelos Teóricos , Refractometría/métodos , Resonancia por Plasmón de Superficie/métodos , Simulación por Computador , Cristalización , Luz , Dispersión de RadiaciónRESUMEN
BACKGROUND: Pancreatodigestive tract anastomotic site stenosis is a problematic complication after pancreatoduodenectomy. OBJECTIVE: We evaluated the feasibility and efficacy of endoscopic treatments for a stenotic pancreatodigestive tract anastomosis. DESIGN: Retrospective study. SETTING: Endoscopic units of a university-affiliated hospital and a general hospital. PATIENTS: Fourteen patients with recurrent pancreatitis (n=10) and pancreatic fluid fistula (n=4) after anatomy-altering surgery with pancreatodigestive tract anastomosis. INTERVENTIONS: The initial ERCP included obtaining a pancreatogram, introducing a 0.025-inch guidewire through the anastomosis, along which a 5F plastic stent or nasopancreatic drain was inserted. If initial ERCP failed, we attempted EUS-guided rendezvous, with a guidewire passed antegrade from the main pancreatic duct across the stenotic anastomosis. MAIN OUTCOME MEASUREMENTS: Rates of successful intervention and clinical relief. RESULTS: The initial intervention was successfully achieved in 6 of 14 patients (38%). Of the 6 patients with successful therapeutic endoscopies, 4 (66.7%) and 2 (25.0%) had undergone a previous pancreatogastrostomy or pancreatojejunostomy, respectively. Eight patients with an initial unsuccessful intervention successfully underwent a second intervention using an EUS-guided or US-guided rendezvous method. Finally, stenosis was relieved in all patients with either the retrograde placement of a pancreatic duct stent across the stenosis of an anastomotic site or antegrade percutaneous bougienage of the stenotic anastomosis. LIMITATIONS: Small sample size and lack of control patients. CONCLUSIONS: Endoscopic treatment of stenotic pancreatodigestive tract anastomosis for transanastomotic pancreatic juice drainage is safe and feasible.
Asunto(s)
Endoscopía del Sistema Digestivo/métodos , Gastrostomía/métodos , Páncreas/cirugía , Pancreaticoduodenectomía/efectos adversos , Estómago/cirugía , Adulto , Anciano , Anastomosis Quirúrgica/efectos adversos , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 72-year-old women was referred to our hospital because of lower left abdominal pain. Computed tomography showed prominent sigmoid colon dilation and double tumors on both the oral and anal sides. Surgical resection revealed an expanded sigmoid colon involved in double cancer that showed strong adhesion to the surrounding tissues. The pathological findings revealed obstructive colitis and minor perforation in the dilated colon. The minor perforation was considered to have been caused by fecal impaction in the closed cavity between the two tumors, resulting in an increase in colon pressure.
Asunto(s)
Adenocarcinoma , Colitis , Perforación Intestinal , Neoplasias del Colon Sigmoide , Adenocarcinoma/complicaciones , Anciano , Colon Sigmoide/diagnóstico por imagen , Femenino , Humanos , Perforación Intestinal/diagnóstico por imagen , Perforación Intestinal/etiología , Neoplasias del Colon Sigmoide/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Notch/Hes1 signaling has been shown to play a role in determining the fate of pancreatic progenitor cells. However, its function in postnatal pancreatic maturation is not fully elucidated. METHODS: We generated conditional Hes1 knockout and/or Notch intracellular domain (NICD) overexpression mice in Ptf1a- or Pdx1-positive pancreatic progenitor cells and analyzed pancreatic tissues. RESULTS: Both Ptf1acre/+; Hes1f/f and Ptf1acre/+; Rosa26NICD mice showed normal pancreatic development at P0. However, exocrine tissue of the pancreatic tail in Ptf1acre/+; Hes1f/f mice atrophied and was replaced by fat tissue by 4 weeks of age, with increased apoptotic cells and fewer centroacinar cells. This impaired exocrine development was completely rescued by NICD overexpression in Ptf1acre/+; Hes1f/f; Rosa26NICD mice, suggesting compensation by a Notch signaling pathway other than Hes1. Conversely, Pdx1-Cre; Hes1f/f mice showed impaired postnatal exocrine development in both the pancreatic head and tail, revealing that the timing and distribution of embryonic Hes1 expression affects postnatal exocrine tissue development. CONCLUSIONS: Notch signaling has an essential role in pancreatic progenitor cells for the postnatal maturation of exocrine tissue, partly through the formation of centroacinar cells.
Asunto(s)
Páncreas/metabolismo , Factor de Transcripción HES-1/farmacología , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Modelos Animales de Enfermedad , Ratones , Transducción de Señal/fisiología , Células Madre/metabolismo , Células Madre/fisiologíaRESUMEN
Three-dimensional (3D) photonic crystals can block photons in any direction and are expected to make possible their ultimate control. However, creating 3D crystals without any unintentional defects over large areas at optical wavelengths has been challenging. For example, opal-based crystals inevitably contain unintentional defects, it is difficult to increase the sizes of micro-manipulated crystals over approximately 6 microm and producing stacked 3D crystals with thin 2D layers requires complicated and time-consuming processes. So far, these difficulties have hindered 3D photonic-crystal research. Here, we demonstrate a novel top-down approach to creating 3D crystals that overcomes these difficulties and significantly simplifies the process. We have developed a double-angled deep-etching method, which enables the direct creation of 3D woodpile crystals in single-crystalline silicon. A strong photonic bandgap effect with >20 dB attenuation in all directions has been achieved. Furthermore, bonding a light emitter onto or between 3D crystals created in this way has been shown to enhance or suppress spontaneous emission.
RESUMEN
Chronic pancreatitis (CP) is a progressive inflammatory disease that eventually results in the impairment of exocrine and endocrine functions of the pancreas. Recent studies have shown an association between mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene and CP. SPINK1 provides the first line of defense against prematurely activated trypsinogen by physically blocking the active site of trypsin. The IVS3+2T>C (c.194+2T>C) mutation is a loss-of-function splicing mutation; it affects the consensus splicing donor site in intron 3 and may cause the skipping of the entire exon 3, where the trypsin-binding site is located. We report here three CP patients carrying this mutation in a homozygous form, with no noticeable family history of pancreatitis. The first patient is a 25-year-old male with juvenile-onset idiopathic CP. He suffered from repeated attacks of pancreatitis since 5 years old and underwent pancreatico-jejunostomy. He complained of epigastralgia, and was diagnosed as obstructive pancreatitis in the area of the accessory pancreatic duct. The second patient is a 75-year-old male with alcoholic CP. He did not have apparent attacks of pancreatitis, but had numerous calcifications throughout the pancreas and confirmed exocrine failure and diabetes mellitus. The last patient is a 44-year-old female with late-onset idiopathic CP. She suffered from repeated attacks of pancreatitis since 32 years old. She had numerous stones in the main pancreatic duct in the pancreas head and confirmed exocrine failure. The clinical courses of these patients are apparently different, indicating the phenotypic variability of the SPINK1 IVS3+2T>C mutation-associated CP.
Asunto(s)
Mutación/genética , Pancreatitis Crónica/genética , Inhibidor de Tripsina Pancreática de Kazal/genética , Adulto , Anciano , Alcohólicos , Exones , Femenino , Enfermedades Genéticas Congénitas/genética , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , Homocigoto , Humanos , Intrones , Masculino , Miopatía del Núcleo Central/genética , Atrofia Óptica Autosómica Dominante/genética , Pancreatitis/genética , Pancreatitis Alcohólica/genética , Serina Proteasas , Inhibidores de Serina Proteinasa/genética , Tripsina/genética , Trastornos Innatos del Ciclo de la UreaRESUMEN
Stenotic pancreatico-enteric anastomosis is one of the serious late complications after a pancreaticoduodenectomy. We report a case of stenotic pancreaticojejunostomy with a pancreatic juice fistula drained externally, which was treated using percutaneous procedures combined with a rendezvous method. A 77-year-old woman was referred to our hospital for an endoscopic treatment to remove a percutaneous drainage tube from a fluid collection due to pancreatic juice fistula. She had undergone pylorus-preserving pancreatoduodenectomy with Roux-en-Y reconstruction due to duodenal carcinoma of Vater's papilla 1 year before the referral to our hospital. Soon after the operation, she had developed a fluid collection adjacent to the anastomosis due to pancreatic juice fistulas and subsequently had undergone its percutaneous drainage. After admission, we tried to dilate the stenotic anastomosis with an endoscopic procedure from the anastomosed jejunal lumen, using an oblique-viewing endoscope. The endoscope reached a portion of the anastomosis, but did not allow us to visualize the entire anastomosis. We punctured the main pancreatic duct under ultrasonography and fluoroscopy, and advanced the needle into the anastomosed jejunum through the stenotic anastomosis. After putting a guidewire into the anastomosed jejunum through the needle, we introduced an oblique-viewing endoscope into the anastomosed jejunum and caught hold of the guidewire using grasping forceps. Maintaining tension on the guidewire with a slight pulling force, with some effort we were able to place a 5-Fr drainage catheter into the jejunum percutaneously and through the anastomosis via the main pancreatic duct. Three weeks after these procedures, we performed balloon dilation of the anastomosis. One week after balloon dilation, removed the percutaneous catheter.
Asunto(s)
Endoscopía del Sistema Digestivo/métodos , Conductos Pancreáticos/cirugía , Pancreatoyeyunostomía/efectos adversos , Pancreatitis/cirugía , Punciones/métodos , Anciano , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Estudios de Seguimiento , Humanos , Pancreatitis/etiologíaRESUMEN
Endoscopic retrograde cholangiopancreatography (ERCP) in patients after Billroth II or Roux-en-Y reconstruction is challenging because of difficulties in insertion of the endoscope into the afferent loop, which is a great distance away from the papilla of Vater, and cannulation into the desired duct from a reverse position. To facilitate ERCP, various endoscopes have been selected according to operator preference. Previously, we reported that an oblique-viewing endoscope (XK-200; Olympus, Tokyo, Japan) can contribute to successful performance of ERCP and associated procedures in Billroth II gastrectomy patients. We report here our experience with two post-gastrectomy patients with chronic pancreatitis who were treated with an oblique-viewing endoscope from the minor papilla.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Endoscopios , Gastrectomía , Gastroenterostomía , Seudoquiste Pancreático/cirugía , Pancreatitis Crónica/cirugía , Adulto , Humanos , Masculino , Persona de Mediana Edad , Conductos Pancreáticos , Seudoquiste Pancreático/diagnóstico , Seudoquiste Pancreático/etiología , Pancreatitis Crónica/diagnóstico , Pancreatitis Crónica/etiologíaRESUMEN
Intrahepatic cholangiocarcinoma (ICC) is frequently driven by aberrant KRAS activation and develops in the liver with chronic inflammation. Although the Notch signaling pathway is critically involved in ICC development, detailed mechanisms of Notch-driven ICC development are still unknown. Here, we use mice whose Notch signaling is genetically engineered to show that the Notch signaling pathway, specifically the Notch/Hes1 axis, plays an essential role in expanding ductular cells in the liver with chronic inflammation or oncogenic Kras activation. Activation of Notch1 enhanced the development of proliferating ductal cells (PDC) in injured livers, while depletion of Hes1 led to suppression. In correlation with PDC expansion, ICC development was also regulated by the Notch/Hes1 axis and suppressed by Hes1 depletion. Lineage-tracing experiments using EpcamcreERT2 mice further confirmed that Hes1 plays a critical role in the induction of PDC and that ICC could originate from PDC. Analysis of human ICC specimens showed PDC in nonneoplastic background tissues, confirming HES1 expression in both PDC and ICC tumor cells. Our findings provide novel direct experimental evidence that Hes1 plays an essential role in the development of ICC via PDC. SIGNIFICANCE: This study contributes to the identification of the cells of origin that initiate ICC and suggests that HES1 may represent a therapeutic target in ICC.
Asunto(s)
Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Factor de Transcripción HES-1/genética , Factor de Transcripción HES-1/metabolismo , Animales , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Dieta/efectos adversos , Humanos , Ratones Noqueados , Ratones Transgénicos , Proteínas Proto-Oncogénicas p21(ras)/genética , Receptores Notch/metabolismoRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) features abundant stromal cells with an excessive extracellular matrix (ECM), termed the desmoplastic reaction. CXCR4 is a cytokine receptor for stromal cell-derived factor-1 (CXCL12) expressed in PDAC, but its roles in PDAC and the characteristic desmoplastic reaction remain unclear. Here, we generated a mouse model of PDAC with conditional knockout of Cxcr4 (KPC-Cxcr4-KO) by crossing Cxcr4 flox mice with Pdx1-Cre;KrasLSL-G12D/+;Trp53LSL-R172H/+ (KPC-Cxcr4-WT) mice to assess the development of pancreatic intraepithelial neoplasia (PanIN) and pancreatic cancers. Tumor cell characteristics of those two types were analyzed in vitro. In addition, CXCR4 expression in human pancreatic cancer specimens was evaluated by IHC staining. In KPC-Cxcr4-KO mice, the number and pathologic grade of PanIN lesions were reduced, but the frequency of pancreatic cancers did not differ from that in KPC-Cxcr4-WT mice. The pancreatic tumor phenotype in KPC-Cxcr4-KO mice was significantly larger and undifferentiated, characterized by abundant vimentin-expressing cancer cells, significantly fewer fibroblasts, and markedly less deposition of ECM. In vitro, KPC-Cxcr4-KO tumor cells exhibited higher proliferative and migratory activity than KPC-Cxcr4-WT tumor cells. Myofibroblasts induced invasion activity in KPC-Cxcr4-WT tumor cells, showing an epithelial-mesenchymal interaction, whereas KPC-Cxcr4-KO tumor cells were unaffected by myofibroblasts, suggesting their unique nature. In human pancreatic cancer, undifferentiated carcinoma did not express CXCR4 and exhibited histologic and IHC features similar to those in KPC-Cxcr4-KO mice. In summary, the CXCL12/CXCR4 axis may play an important role in the desmoplastic reaction in PDAC, and loss of CXCR4 induces phenotype changes in undifferentiated carcinoma without a desmoplastic reaction. SIGNIFICANCE: The current study uncovers CXCR4 as a key regulator of desmoplastic reaction in PDAC and opens the way for new therapeutic approaches to overcome the chemoresistance in patients with PDAC.
Asunto(s)
Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/patología , Receptores CXCR4/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Diferenciación Celular/genética , Movimiento Celular , Quimiocina CXCL12/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas Experimentales/patología , Neoplasias Hepáticas Experimentales/secundario , Ratones Endogámicos C57BL , Ratones Noqueados , Miofibroblastos/metabolismo , Miofibroblastos/patología , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/genéticaRESUMEN
Pancreatic neuroendocrine tumors (PanNET) were classified into grades (G) 1 to 3 by the World Health Organization in 2017, but the precise mechanisms of PanNET initiation and progression have remained unclear. In this study, we used a genetically engineered mouse model to investigate the mechanisms of PanNET formation. Although pancreas-specific deletion of the Rb gene (Pdx1-Cre;Rbf/f ) in mice did not affect pancreatic exocrine cells, the α-cell/ß-cell ratio of islet cells was decreased at 8 months of age. During long-term observation (18-20 months), mice formed well-differentiated PanNET with a Ki67-labeling index of 2.7%. In contrast, pancreas-specific induction of a p53 mutation (Pdx1-Cre;Trp53R172H ) had no effect on pancreatic exocrine and endocrine tissues, but simultaneous induction of a p53 mutation with Rb gene deletion (Pdx1-Cre;Trp53R172H;Rb f/f ) resulted in the formation of aggressive PanNET with a Ki67-labeling index of 24.7% over the short-term (4 months). In Pdx1-Cre;Trp53R172H;Rbf/f mice, mRNA expression of Pten and Tsc2, negative regulators of the mTOR pathway, significantly decreased in the islet cells, and activation of the mTOR pathway was confirmed in subsequently formed PanNET. Thus, by manipulating Rb and p53 genes, we established a multistep progression model from dysplastic islet to indolent PanNET and aggressive metastatic PanNET in mice. These observations suggest that Rb and p53 have distinct roles in the development of PanNET. SIGNIFICANCE: Pancreas-specific manipulation of Rb and p53 genes induced malignant transformation of islet cells, reproducing stepwise progression from microadenomas to indolent (grade 1) and subsequent aggressive PanNETs (grade 2-3).
Asunto(s)
Transformación Celular Neoplásica/genética , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/genética , Proteína de Retinoblastoma/genética , Proteína p53 Supresora de Tumor/genética , Animales , Ratones , Ratones TransgénicosRESUMEN
BACKGROUND: Marked duodenal stenosis makes endoscopic biliary stenting (EBS) impossible, although it is the most common method for treating obstructive jaundice in patients with benign or malignant biliary strictures. Large-balloon dilation can be used to enable endoscope passage in the GI tract. OBJECTIVE: We describe 4 cases of successful EBS combined with the use of a large balloon for the treatment of difficult duodenal strictures in patients with benign and malignant biliary strictures. DESIGN: A retrospective case series. SETTING: Two tertiary referral centers. PATIENTS: Four patients: 1 with hilar carcinoma, 1 with gallbladder carcinoma, and 2 with chronic pancreatitis. INTERVENTIONS: After duodenal dilation, the slightly deflated balloon was pushed with the endoscope into the major papilla through the duodenal stricture (pushing method used in 2 patients). In the cases in which the major papilla was not accessible with the pushing method, a large dilation balloon was deflated completely after dilation, advanced beyond the stricture into the third portion of the duodenum, and reinflated to the maximum size. Pulling the dilation balloon catheter into the working channel while hooking the inflated balloon as the anchor at the anal side of the duodenal stricture, the endoscope was straightened to advance to the major papilla (hooking method used in 2 patients). MAIN OUTCOME MEASUREMENT: Successful EBS. RESULTS: Reaching the major papilla and EBS was accomplished in all 4 patients. LIMITATION: Small number of cases. CONCLUSIONS: Use of large-balloon dilation can contribute to successful ERCP in patients with difficult duodenal strictures.
Asunto(s)
Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Colangitis/terapia , Colestasis/terapia , Obstrucción Duodenal/terapia , Stents , Adulto , Anciano , Ampolla Hepatopancreática , Colangitis/diagnóstico por imagen , Colangitis/mortalidad , Colestasis/diagnóstico por imagen , Colestasis/mortalidad , Obstrucción Duodenal/diagnóstico por imagen , Obstrucción Duodenal/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: We report that an oblique-viewing endoscope facilitates endoscopic retrograde cholangiopancreatography (ERCP) in Billroth II reconstruction. With this endoscope, we carried out ERCP in Roux-en-Y reconstruction. METHODS: Fifteen patients with Roux-en-Y reconstruction were enrolled. Eleven of these patients had undergone gastrectomy, while Whipple's operation or choledochectomy had each been carried out in two patients. Among the 11 post-gastrectomy patients, eight had bile duct stones, and there was one case each of pancreatic abscess with chronic pancreatitis, bile duct obstruction due to gallbladder, or pancreatic cancer. The remaining four patients suffered from stenotic anastomosis of choledochojejunostomy. All procedures were carried out with an oblique-viewing endoscope. RESULTS: The papilla of Vater or anastomosis was reached in 10 patients. In these 10 patients, all planned procedures were completed. Endoscopic papillary balloon dilatation (EPBD) was carried out in three patients with bile duct stones. The remaining three patients with bile duct stones underwent sphincterotomy with tube stent placement, EPBD after sphincterotomy with biliary tube stent placement, and biliary tube stent placement, respectively. Pancreatic stent placement via the minor papilla was carried out in one patient with pancreatic abscess, and a biliary tube stent was introduced in the patient with gallbladder cancer. Two patients underwent cutting of a stenotic anastomosis with a needle knife, followed by balloon dilatation. None of the patients experienced any complications. CONCLUSION: The results appear to support the feasibility of using an oblique-viewing endoscope for ERCP in Roux-en-Y reconstruction. Further studies including a large population of patients should be planned to confirm these results.
Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/instrumentación , Yeyuno/cirugía , Estómago/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis en-Y de Roux , Conducto Colédoco/cirugía , Endoscopios , Femenino , Gastrectomía , Gastroenterostomía , Humanos , Masculino , Persona de Mediana Edad , PancreaticoduodenectomíaRESUMEN
A 46-year-old female patient was referred to our hospital for endoscopic treatment of stenotic pancreatogastrostomy. She had undergone pylorus-preserving pancreatoduodenectomy due to duodenal carcinoma of the papilla of Vater 5 years before referral. Two years after the operation, she had to be hospitalized several times during a 1-year period because of acute recurrent pancreatitis caused by stenosis of the anastomosis of the pancreatoduodenostomy. An endoscopic ultrasound (EUS)-guided rendezvous technique was selected to puncture the main pancreatic duct via a transgastric approach. We identified the dilated main pancreatic duct with a convex array echoendoscope from the lower gastric body near the anastomosis and successfully punctured the dilated main pancreatic duct. The guidewire passed through the stenosis to the gastric cavity and we could place a stent through the stenotic anastomosis. After the procedure, the patient has not experienced acute recurrent pancreatitis for 9 months. Pancreatogastrostomy has been the preferred method used to carry out post-pancreatoduodenectomy reconstruction. However, stenosis of the anastomosis has been reported as one of the late complications of pancreatogastrostomy. The main symptom of this complication is recurrent epigastralgia due to obstructive pancreatitis. As a result, patients are compelled to stay in the hospital for an extended duration with no oral intake allowed. Surgical resection of the stenosis is often the treatment of choice but can be troublesome due to post-operative adhesions. Here, we report a case of pancreatogastrostomy complicated by stenosis, which was treated using the EUS-guided rendezvous technique.