Plastic pigtail vs lumen-apposing metal stents for drainage of walled-off necrosis (PROMETHEUS study): an open-label, multicenter randomized trial.

BACKGROUND: Lumen-apposing metal stents (LAMS) have displaced double-pigtail plastic stents (DPS) as the standard treatment for walled-off necrosis (WON),ß but evidence for exclusively using LAMS is limited. We aimed to assess whether the theoretical benefit of LAMS was superior to DPS. METHODS: This multicenter, open-label, randomized trial was carried out in 9 tertiary hospitals. Between June 2017, and Oct 2020, we screened 99 patients with symptomatic WON, of whom 64 were enrolled and randomly assigned to the DPS group (n = 31) or the LAMS group (n = 33). The primary outcome was short-term (4-weeks) clinical success determined by the reduction of collection. Secondary endpoints included long-term clinical success, hospitalization, procedure duration, recurrence, safety, and costs. Analyses were by intention-to-treat. CLINICALTRIALS: gov, NCT03100578. RESULTS: A similar clinical success rate in the short term (RR, 1.41; 95% CI 0.88-2.25; p = 0.218) and in the long term (RR, 1.2; 95% CI 0.92-1.58; p = 0.291) was observed between both groups. Procedure duration was significantly shorter in the LAMS group (35 vs. 45-min, p = 0.003). The hospital admission after the index procedure (median difference, - 10 [95% CI - 17.5, - 1]; p = 0.077) and global hospitalization (median difference - 4 [95% CI - 33, 25.51]; p = 0.82) were similar between both groups. Reported stent-related adverse events were similar for the two groups (36 vs.45% in LAMS vs. DPS), except for de novo fever, which was significantly 26% lower in LAMS (RR, 0.26 [0.08-0.83], p = 0.015). CONCLUSIONS: The clinical superiority of LAMS over DPS for WON therapy was not proved, with similar clinical success, hospital stay and similar safety profile between both groups, yet a significant reduction in procedure time was observed. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT03100578.

The involvement of the hepatic artery is a risk factor for unresectability after neoadjuvant treatment in borderline pancreatic adenocarcinoma.

INTRODUCTION: Borderline Resectable Pancreatic Ductal Adenocarcinoma (BR-PDAC) benefits from neoadjuvant treatment (NAT) with the intent of surgical salvage in the absence of disease progression during chemotherapy (CT) or chemoradiotherapy (CRT). Scarce literature exists about prognostic factors of resectability at the time of diagnosis or during neoadjuvant treatment, especially regarding vascular relationships. MATERIALS: We reviewed our prospective BR-PDAC cohort to determine resectability predictors. We collected data about clinical baseline characteristics, vessels' involvement, type of NAT, CA19-9 evolution, and radiological outcome. We performed a descriptive analysis and a logistic regression model to define resectability predictors; we finally compared overall survival (OS) and progression-free survival (PFS) for those predictors. RESULTS: One hundred patients started NAT, with a resection rate of 44 % (40 pancreaticoduodenectomies, 4 distal pancreatectomies). The most frequent vessel relationship was the abutment of the superior mesenteric artery (44 %), and 26 patients had ≥2 vessels involved. Prognostic factors of resectability were CA19-9 response >10 % (OR 3.07, p = 0.016) and Hepatic Artery involvement (OR 0.21, p = 0.026). Median overall survival was better for CA19-9 responders than for non-responders (20.9 months and 11.8 months respectively, p < 0.001), and similar to normalized CA19-9 (25.0 months, p = 0.48). There were no differences in terms of OS or PFS with the involvement of the HA (17.7 vs 17.1 months, p = 0.367; and 8.7 vs 12.0 months, p = 0.267). CONCLUSION: The involvement of the Hepatic Artery seems to confer a worse prognosis regarding resectability. A decrease of only >10 % of CA19-9 is a predictive factor for resectability and better overall and progression-free survival.

Nonfunctioning, small, incidental pancreatic neuroendocrine tumors: Results of a nonoperative approach cohort. / Tumores neuroendocrinos no funcionantes de páncreas incidentales de pequeño tamaño: Resultados de una serie con manejo no quirúrgico.

OBJECTIVE: The availability of new imaging techniques has conditioned an increase in the incidental diagnosis of small nonfunctioning pancreatic neuroendocrine tumors (PNET-NF). The best treatment is controversial, some authors advise a conservative approach in selected cases. Our aim is to analyze the evolution of incidental, small size PNET-NF, treated with clinical follow-up without surgery. METHODS: We performed a retrospective analysis of a prospective database of patients diagnosed incidentally with PNET-NF since November 2007 to September 2015. We include those with PNET-NF ≤2cm and asymptomatic. The diagnosis was performed using imaging tests indicating endoscopic ultrasound-guided fine-needle aspiration in case of doubts in the diagnosis. The follow-up was performed at our center, registering clinical and/or radiological changes. RESULTS: We included 24 patients with a median age of 70 years, and a similar distribution in terms of sex. The diagnosis was made through computed tomography multidetector or magnetic resonance imaging and octreotide scan. The tumors were located mainly in the head and neck (46%), with a mean size of 11,5±3,55mm at diagnosis (5-19mm). In 2 cases endoscopic ultrasound fine needle aspiration was used (8%), confirming the diagnosis of low-grade PNET with Ki67<5%. The median follow-up was 39 months (7-100). In 19 patients (79%) they remained the same size, 21% (5) increased its size with a mean of 2,6±2mm (1-6). No cases had progression of disease. CONCLUSION: In selected patients, non-surgical management of PNET-NF is an option to consider, when they are asymptomatic and ≤2cm. Larger studies with more patients and more time of follow-up are needed to validate this non-operative approach.

Tumores neuroendocrinos no funcionantes de páncreas incidentales de pequeno tamano: Resultados de una serie con manejo no quirúrgico / Nonfunctioning, small, incidental pancreatic neuroendocrine tumors. Results of a nonoperative approach cohort

OBJETIVO: La disponibilidad de nuevas técnicas de imagen ha condicionado un incremento en el diagnóstico incidental de pequeños tumores neuroendocrinos pancreáticos no funcionantes (TNP-NF). El mejor tratamiento de estos tumores es controvertido: algunos autores aconsejan una actitud conservadora en casos seleccionados. Nuestro objetivo es analizar la evolución de TNP-NF incidentales de pequeño tamaño, tratados con seguimiento clínico sin cirugía. MÉTODOS: Se realizó un análisis retrospectivo de una base de datos prospectiva de pacientes diagnosticados incidentalmente de TNP-NF desde noviembre de 2007 hasta septiembre de 2015. Incluimos aquellos con TNP-NF≤2 cm y asintomáticos. El diagnóstico se realizó mediante pruebas de imagen, indicando ecoendoscopia-punción en caso de dudas diagnósticas. El seguimiento se hizo en nuestro centro, con registro de cambios clínicos y radiológicos. RESULTADOS:Incluimos a 24 pacientes con una mediana de edad de 70 años y distribución similar en cuanto al sexo. El diagnóstico se realizó mediante tomografía computarizada multidetector, resonancia nuclear magnética y gammagrafía con octreótide. Los tumores se localizaban principalmente en cabeza y cuello (46%), con un tamaño medio de 11,5 ± 3,55 mm al diagnóstico (5-19 mm). En 2 casos se asoció ecoendoscopia-punción (8%), confirmando el diagnóstico de TNP de bajo grado con Ki67 < 5%. La mediana de seguimiento fue de 39 meses (7-100). El 79% (19) mantuvieron el mismo tamaño. El 21% (5) aumentó su tamaño con una media de 2,6±2mm (1-6). En ningún caso hubo progresión de enfermedad. CONCLUSIÓN: En pacientes seleccionados, el manejo no quirúrgico de TNP-NF, asintomáticos y ≤ 2cm es una opción a tener en cuenta. Son necesarios estudios con mayor número de pacientes y un seguimiento mayor para validar esta opción conservadora

OBJECTIVE: The availability of new imaging techniques has conditioned an increase in the incidental diagnosis of small nonfunctioning pancreatic neuroendocrine tumors (PNET-NF). The best treatment is controversial, some authors advise a conservative approach in selected cases. Our aim is to analyze the evolution of incidental, small size PNET-NF, treated with clinical follow-up without surgery. METHODS: We performed a retrospective analysis of a prospective database of patients diagnosed incidentally with PNET-NF since November 2007 to September 2015. We include those with PNET-NF ≤ 2cm and asymptomatic. The diagnosis was performed using imaging tests indicating endoscopic ultrasound-guided fine-needle aspiration in case of doubts in the diagnosis. The follow-up was performed at our center, registering clinical and/or radiological changes. RESULTS: We included 24 patients with a median age of 70 years, and a similar distribution in terms of sex. The diagnosis was made through computed tomography multidetector or magnetic resonance imaging and octreotide scan. The tumors were located mainly in the head and neck (46%), with a mean size of 11,5 ± 3,55 mm at diagnosis (5-19 mm). In 2 cases endoscopic ultrasound fine needle aspiration was used (8%), confirming the diagnosis of low-grade PNET with Ki67 < 5%. The median follow-up was 39 months (7-100). In 19 patients (79%) they remained the same size, 21% (5) increased its size with a mean of 2,6 ± 2 mm (1-6). No cases had progression of disease. CONCLUSION: In selected patients, non-surgical management of PNET-NF is an option to consider, when they are asymptomatic and ≤ 2 cm. Larger studies with more patients and more time of follow-up are needed to validate this non-operative approach

Tratamiento quirúrgico de los tumores neuroendocrinos no funcionantes de páncreas basado en 3 escenarios clínicos / Surgical treatment of non-functioning pancreatic neuroendocrine tumours based on three clinical scenarios

INTRODUCCIÓN: El tratamiento de los tumores neuroendocrinos pancreáticos no funcionantes (TNEPNF) es la resección en caso de enfermedad localizada o metástasis hepáticas resecables. Existe controversia en metástasis hepáticas irresecables. MÉTODOS: Analizamos los datos perioperatorios y de supervivencia de 63 pacientes resecados por TNEPNF entre 1993 y 2012, dividiéndolos en 3 escenarios: A, resección pancreática (44 pacientes); B, resección pancreática y hepática por metástasis hepáticas sincrónicas (12 pacientes), y C, resección pancreática en presencia de metástasis hepáticas irresecables (6 pacientes). Se estudiaron factores pronósticos de supervivencia y recidiva. RESULTADOS: Las cirugías más frecuentes fueron, pancreatectomía corporocaudal (51%) y duodenopancreatectomía cefálica (38%). El 44% de los pacientes requirieron una cirugía asociada, resecando sincrónicamente páncreas e hígado en 9. Dos pacientes recibieron un trasplante hepático durante el seguimiento. Según la clasificación de la OMS, se distribuyeron en G1: 10 (16%), G2: 45 (71%) y G3: 8 (13%). La morbimortalidad postoperatoria fue del 49 y del 1,6%, respectivamente. Al cierre del estudio, 43 (68%) seguían vivos, con una supervivencia actuarial media de 9,6 años. La clasificación de la OMS y la recidiva fueron factores de riesgo de mortalidad en el estudio multivariante. La supervivencia actuarial mediana por escenarios fue de 131 meses (A), 102 meses (B) y 75 meses (C), sin diferencias estadísticamente significativas. CONCLUSIONES: El tratamiento del TNEPNF sin enfermedad a distancia es la resección. Las metástasis hepáticas resecables en los tumores bien diferenciados deben resecarse. La resección del tumor pancreático con metástasis hepáticas sincrónicas irresecables debe considerarse en TNEPNF bien diferenciados. El grado de clasificación de la OMS y la recidiva son factores de riesgo de mortalidad a largo plazo

INTRODUCTION: The treatment of patients with non-functioning pancreatic neuroendocrine tumours (NFPNET) is resection in locally pancreatic disease, or with resectable liver metastases. There is controversy about unresectable liver disease. METHODS: We analysed the perioperative data and survival outcome of 63 patients who underwent resection of NFPNET between 1993 and 2012. They were divided into 3 scenarios: A, pancreatic resection (44 patients); B, pancreatic and liver resection in synchronous resectable liver metastases (12 patients); and C, pancreatic resection in synchronous unresectable liver metastases (6 patients). The prognostic factors for survival and recurrence were studied. RESULTS: Distal pancreatectomy (51%) and pancreaticoduodenectomy (38%) were more frequently performed. Associated surgery was required in 44% of patients, including synchronous liver resections in 9 patients. Two patients received a liver transplant during follow-up. According to the WHO classification they were distributed into G1: 10 (16%), G2: 45 (71%), and G3: 8 (13%). The median hospital stay was 11 days. Postoperative morbidity and mortality were 49% and 1.6%, respectively. At the closure of the study, 43 (68%) patients were still alive, with a mean actuarial survival of 9.6 years. The WHO classification and tumour recurrence were risk factors of mortality in the multivariate analysis. The median actuarial survival by scenarios was 131 months (A), 102 months (B), and 75 months (C) without statistically significant differences. CONCLUSIONS: Surgical resection is the treatment for NFPNET without distant disease. Resectable liver metastases in well-differentiated tumours must be resected. The resection of the pancreatic tumour with unresectable synchronous liver metastasis must be considered in well-differentiated NFPNET. The WHO classification grade and recurrence are risk factors of long-term mortality

Surgical treatment of non-functioning pancreatic neuroendocrine tumours based on three clinical scenarios. / Tratamiento quirúrgico de los tumores neuroendocrinos no funcionantes de páncreas basado en 3 escenarios clínicos.

INTRODUCTION: The treatment of patients with non-functioning pancreatic neuroendocrine tumours (NFPNET) is resection in locally pancreatic disease, or with resectable liver metastases. There is controversy about unresectable liver disease. METHODS: We analysed the perioperative data and survival outcome of 63 patients who underwent resection of NFPNET between 1993 and 2012. They were divided into 3 scenarios: A, pancreatic resection (44patients); B, pancreatic and liver resection in synchronous resectable liver metastases (12patients); and C, pancreatic resection in synchronous unresectable liver metastases (6patients). The prognostic factors for survival and recurrence were studied. RESULTS: Distal pancreatectomy (51%) and pancreaticoduodenectomy (38%) were more frequently performed. Associated surgery was required in 44% of patients, including synchronous liver resections in 9patients. Two patients received a liver transplant during follow-up. According to the WHO classification they were distributed into G1: 10 (16%), G2: 45 (71%), and G3: 8 (13%). The median hospital stay was 11days. Postoperative morbidity and mortality were 49% and 1.6%, respectively. At the closure of the study, 43 (68%) patients were still alive, with a mean actuarial survival of 9.6years. The WHO classification and tumour recurrence were risk factors of mortality in the multivariate analysis. The median actuarial survival by scenarios was 131months (A), 102months (B), and 75months (C) without statistically significant differences. CONCLUSIONS: Surgical resection is the treatment for NFPNET without distant disease. Resectable liver metastases in well-differentiated tumours must be resected. The resection of the pancreatic tumour with unresectable synchronous liver metastasis must be considered in well-differentiated NFPNET. The WHO classification grade and recurrence are risk factors of long-term mortality.

Tratamiento quirúrgico del adenocarcinoma pancreático mediante duodenopancreatectomía cefálica (parte 2). Seguimiento a largo plazo tras 204 casos / Surgical treatment of pancreatic adenocarcinoma using cephalic duodenopancreatectomy (Part 2). Long term follow up after 204 cases

Objetivo: Definir factores pronóstico de supervivencia a largo plazo tras la duodenopancreatectomía cefálica por adenocarcinoma pancreático. Introducción: La cirugía es el tratamiento aceptado en el adenocarcinoma de páncreas cefálico, sin embargo la supervivencia a largo plazo sigue siendo baja. Material y métodos: Hemos recogido la experiencia en el tratamiento del adenocarcinoma de cabeza de páncreas (ADCP) en el Hospital Universitari de Bellvitge mediante duodenopancreatectomía cefálica (DPC) desde 1991 hasta 2007. Resultados: Se realizaron 204 DPC por ADCP. El estudio histológico evidenció que el tumor resecado tenía un tamaño superior a 3cm. en 70, con permeación linfática en un 73%, invasión perineural en 89% y afectación linfática en 71%. En 120 pacientes se resecaron más de 15 adenopatías. Tras la cirugía, se administró tratamiento adyuvante a 113 pacientes (60%). Se contabilizaron 148 fallecimientos (73%), estando vivos al cierre del mismo 55 (27%). La supervivencia actual media fue de 2,54 años (IC95% 2,02–3,07) y la supervivencia actuarial a 5 años de 13,55% (IC95% 7,69–19,41). El estudio de factores de riesgo de mortalidad reveló que el sexo femenino (p=0,005), la ausencia de transfusión perioperatoria (p=0,003), la resección de más de 15 adenopatías en la intervención (p=0,004) y la administración de tratamiento adyuvante (p=0,004) comportaron mejor pronóstico a largo plazo. El estudio multivariante demostró que transfusión y sexo fueron las variables de interés. Conclusiones: La cirugía del adenocarcinoma de cabeza de páncreas debe incluir una linfadenectomía suficiente y debe realizarse con baja morbilidad y sin necesidad de transfusión perioperatoria (AU)

Introduction: Surgery is the accepted treatment in adenocarcinoma of the head of the pancreas; however, the long-term survival continues to be low. The aim of this study is to define prognos:tic factors of long-term survival after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma. Material and methods: We have collected data on the treatment of adenocarcinoma of the head of the pancreas (ADHP) by means of a cephalic duodenopancreatectomy (CDP) performed n the Bellvitge University Hospital (Barcelona) from 1991 to 2007. Results: A total of 204 CDP due to ADHP were performed. The histology showed that the resected tumour was larger than 3cms in 70 cases, with lymphatic infiltration in 73%, perineural invasion in 89%, and lymphatic involvement in 89%. More than 15 lymph nodes were resected in 120 patients. A total of 113 (60%) patients received adjuvant treatment after surgery. There were 148 (73%) deaths, of which 55 (27%) were alive at closure. The actual mean survival was 2.54 years (95% CI; 2.02–3.07) and an actuarial survival at 5 years of 13.55% (95% CI; 7.69–19.41). The study of mortality risk factors showed that, female gender, absence of peri-operative transfusion (p=0.003), the resection of more than 15 lymph nodes during the operation (P=0.004), and the administration of adjuvant treatment (p=0.004) had a better long-term prognosis. The multivariate analysis showed that transfusion and gender were the most significant variables. Conclusions: Surgery of head of the pancreas adenocarcinoma must include an adequate lymphadectomy, and must be performed with a low morbidity and without the need of a peri-operative transfusion (AU)

[Surgical treatment of pancreatic adenocarcinoma using cephalic duodenopancreatectomy (Part 2). Long term follow up after 204 cases]. / Tratamiento quirúrgico del adenocarcinoma pancreático mediante duodenopancreatectomía cefálica (parte 2). Seguimiento a largo plazo tras 204 casos.

INTRODUCTION: Surgery is the accepted treatment in adenocarcinoma of the head of the pancreas; however, the long-term survival continues to be low. The aim of this study is to define prognostic factors of long-term survival after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma. MATERIAL AND METHODS: We have collected data on the treatment of adenocarcinoma of the head of the pancreas (ADHP) by means of a cephalic duodenopancreatectomy (CDP) performed n the Bellvitge University Hospital (Barcelona) from 1991 to 2007. RESULTS: A total of 204 CDP due to ADHP were performed. The histology showed that the resected tumour was larger than 3cms in 70 cases, with lymphatic infiltration in 73%, perineural invasion in 89%, and lymphatic involvement in 89%. More than 15 lymph nodes were resected in 120 patients. A total of 113 (60%) patients received adjuvant treatment after surgery. There were 148 (73%) deaths, of which 55 (27%) were alive at closure. The actual mean survival was 2.54 years (95% CI; 2.02-3.07) and an actuarial survival at 5 years of 13.55% (95% CI; 7.69-19.41). The study of mortality risk factors showed that, female gender, absence of peri-operative transfusion (p=0.003), the resection of more than 15 lymph nodes during the operation (P=0.004), and the administration of adjuvant treatment (p=0.004) had a better long-term prognosis. The multivariate analysis showed that transfusion and gender were the most significant variables. CONCLUSIONS: Surgery of head of the pancreas adenocarcinoma must include an adequate lymphadectomy, and must be performed with a low morbidity and without the need of a peri-operative transfusion.