Stromal disrupting effects of nab-paclitaxel in pancreatic cancer.

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.

Conventional versus Rosemont endoscopic ultrasound criteria for chronic pancreatitis: interobserver agreement in same day back-to-back procedures.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound (EUS) is a commonly used and fairly sensitive method of assessing changes of chronic pancreatitis (CP) when routine noninvasive imaging has not shown overt features of CP. The aim of this study is to evaluate the interobserver agreement (IOA) for the classic (MSC) and the Rosemont (RC) criteria for the diagnosis of chronic pancreatitis on the basis of clinical practice. PATIENTS AND METHODS: Two experienced endosonographers evaluated on the same day patients referred for EUS in a blinded fashion. Data from the sonographic criteria of both MSC and RC were collected. Agreement was calculated using k statistics. RESULTS: A total of 69 patients were evaluated. The study population included mainly patients without pancreatic diseases, resulting in a low number of sonographic findings. Agreement for the final diagnosis was moderate for both classification systems of chronic pancreatitis (k = 0.53 for conventional and k = 0.46 for Rosemont). CONCLUSIONS: The IOA of EUS in the diagnosis of CP is moderate. The concordance values obtained in clinical practice are similar to those obtained in multicenter studies. The RC does not seem to improve the IOA of MSC.

Impacto clínico de la introducción de la ultrasonografía endoscópica (USE) alta en un hospital de área / No disponible

Objetivos: Evaluar el impacto de la introducción de la ecoendoscopia en la práctica clínica. Métodos: Se analizaron todas las exploraciones realizadas en los primeros 18 meses de implantación de la técnica. Se valoró la concordancia mediante técnicas radiológicas o piezas quirúrgicas en los casos en los que fue posible. Resultados: Se realizaron 277 exploraciones. Sólo se han registrado 2 complicaciones y en ambos casos fue en relación con la sedación. La demanda fue en aumento, alcanzando 70 exploraciones/ 100.000 habitantes. Las indicaciones principales fueron procesos biliares (34,3%) y pancreáticos. No se encontró patología alguna en el 10% de los casos. 29 presentaban coledocolitiasis (93% confirmadas y tratadas endoscópicamente). Se diagnosticaron 19 pancreatitis crónicas (sólo el 15,78% fueron diagnosticadas por tomografía computarizada). Se evaluaron 32 pacientes con pancreatitis aguda idiopática: en 20 de ellos se visualizó microlitiasis (80% fueron colecistectomizados y permanecen asintomáticos tras una media de seguimiento de 21,5 meses), 2 casos de coledocolitiasis, 1 con pancreatitis crónica y 9 casos permanecieron sin filiar la etiología. Hemos realizado 56 punciones: 39 muestras de páncreas en 33 pacientes (fueron diagnósticas en el 81,1%, siendo los diagnósticos más frecuentes el adenocarcinoma y el cistoadenoma seroso), 13 adenopatías y 4 masas abdominales. Conclusiones: La ecoendoscopia es una técnica con una demanda creciente, presenta escasos riesgos y conlleva una mejor toma de decisiones en un importante número de pacientes con enfermedades diversas. Por lo tanto, su inclusión en la práctica clínica rutinaria ha de ser considerado(AU)

Objectives: Evaluation of the impact of EUS in clinical practice. Methods: All exploration performed during the first 18 months of implementation of the technique were analyzed. Agreement was assessed by radiographic techniques or surgical specimens in those cases allowed. Results: 277 exploration were performed. There have been only 2 complications and they were related to sedation in both cases. The demand increased gradually, reaching 70 scans per 100,000 inhabitants. Main indications were bile (34.3%) and pancreatic processes. No pathology was found in 10% of cases; 29 cases had choledocholithiasis (93% confirmed and treated endoscopically). Chronic pancreatitis was diagnosed in 19 cases (only 15.78% of the cases were diagnosed by computed tomography). 32 patients with idiopathic acute pancreatitis were evaluated: 20 of them had evidence of microlithiasis (80% cholecystectomized and asymptomatic after a mean follow-up of 21.5 months), two cases of choledocholithiasis, 1 with chronic pancreatitis and 9 cases remained free of filial etiology. We performed 56 punctures: 39 samples of pancreas in 33 patients (81.1% of the samples were diagnostic; adenocarcinoma and serous cystadenoma were the most common diagnoses), 13 enlarged nodes and 4 abdominal masses. Conclusions: EUS is a growing demand technique that has low risks and leads to better decision-making in a significant number of patients with different diseases. Therefore, its inclusion in routine clinical practice must be considered(AU)

Clinical impact of high-definition endoscopic ultrasonography (EUS) in a district hospital.

OBJECTIVES: Evaluation of the impact of EUS in clinical practice. METHODS: All exploration performed during the first 18 months of implementation of the technique were analyzed. Agreement was assessed by radiographic techniques or surgical specimens in those cases allowed. RESULTS: 277 exploration were performed. There have been only 2 complications and they were related to sedation in both cases. The demand increased gradually, reaching 70 scans per 100,000 inhabitants. Main indications were bile (34.3%) and pancreatic processes. No pathology was found in 10% of cases; 29 cases had choledocholithiasis (93% confirmed and treated endoscopically). Chronic pancreatitis was diagnosed in 19 cases (only 15.78% of the cases were diagnosed by computed tomography). 32 patients with idiopathic acute pancreatitis were evaluated: 20 of them had evidence of microlithiasis (80% cholecystectomized and asymptomatic after a mean follow-up of 21.5 months), two cases of choledocholithiasis, 1 with chronic pancreatitis and 9 cases remained free of filial etiology. We performed 56 punctures: 39 samples of pancreas in 33 patients (81.1% of the samples were diagnostic; adenocarcinoma and serous cystadenoma were the most common diagnoses), 13 enlarged nodes and 4 abdominal masses. CONCLUSIONS: EUS is a growing demand technique that has low risks and leads to better decision-making in a significant number of patients with different diseases. Therefore, its inclusion in routine clinical practice must be considered.