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Antibody-mediated rejection (AMR) after liver transplantation is uncommon but, when present, manifests as graft dysfunction. We report the case of a 54-year-old woman who developed portal hypertension with pleural effusion and ascites secondary to sinusoidal obstruction syndrome (SOS) due to acute AMR following an ABO-matched liver transplantation for autoimmune cirrhosis and hepatocellular carcinoma. Initial immunosuppression comprised basiliximab, decreasing prednisone, tacrolimus, and mycophenolate mofetil. After 1 month, she presented with the massive pleural effusion, slight ascites, and normal liver tests. After excluding common causes of pleural effusion, we performed a liver biopsy that showed atypical rejection with the involvement of large centrilobular veins partially occluded by marked endotheliitis and lax fibrosis suggestive of SOS. Direct immunofluorescence study of C4d showed diffuse endothelial sinusoidal staining, and de novo donor-specific anti-human leukocyte antigen antibodies were detected in his blood. Thus, we diagnosed AMR focused on centrilobular veins and initiated treatment with defibrotide, steroid pulses, and diuretics. However, this was ineffective, and the pleural effusion only resolved when plasmapheresis and intravenous immunoglobulin were started. This case shows that AMR can cause SOS with portal hypertension and present with a pleural effusion, and as such, it should be suspected after excluding other more common causes of effusion.

The main objective of this study was to analyse the results of the surgical treatment of ampullary neuroendocrine tumours (NET) based on transduodenal ampullectomy and pancreatoduodenectomy, in a reference centre in hepatobiliopancreatic pathology.Retrospective, observational study, including all patients operated on for pancreatic and/or duodenal NET in a reference unit of hepatobiliopancreatic pathology and prospectively registered between January 1Of 181 patients operated on for pancreatic and/or duodenal NET, only 9 were located in the ampulla of Vater, which represents 4.9% of all pancreatic and/or duodenal NET. Pancreatoduodenectomy (PD) was performed in 6 patients, while 3 patients underwent transduodenal ampullectomy (TDA). Longer surgical time and more postoperative complications were observed in the PD group. There were no differences in hospital stay. Overall and disease-free survival at 5 years in the PD group compared to ATD was 83.3% vs. 100% and 50% vs. 100%, respectively.Ampullary NET without locoregional involvement or risk factors, can be treated by conservative surgeries such as transduodenal ampullectomy.

Background Annual hospital volume of pancreatoduodenectomies could influence postoperative outcomes. The aim of this study is to establish with a non-arbitrary method the minimum threshold of yearly performed pancreatoduodenectomies in order to improve several postoperative quality outcomes. Method Prospective follow-up of patients submitted to pancreatoduodenectomy in participating hospitals during 1 year. The influence of hospital volume on quality outcomes was analyzed by univariable and multivariable models. The minimum threshold of yearly performed pancreatoduodenectomies to improve outcomes was established by Akaike’s information criteria. Results Data from 877 patients operated in 74 hospitals were analyzed. Of 12 quality outcomes, 9 were influenced by hospital pancreatoduodenectomy volume on multivariable analysis. To decrease the risk of complications and the risk of retrieving an insufficient number of lymph nodes at least 31 pancreatoduodenectomies per year should be performed. To decrease the risk of prolonged length of stay, postoperative death, and affected surgical margins, at least 37, 6, and 14 pancreatoduodenectomies per year should be performed, respectively. Conclusion Several postoperative quality outcomes are influenced by the number of yearly performed pancreatoduodenectomies and could be improved by establishing a minimum threshold of procedures. Number of procedures needed to improve quality outcomes has been established by a non-arbitrary method.

Introduction Intrahepatic cholangiocarcinoma is a primary liver neoplasm whose only curative treatment is surgery. The objective of this study was to determine the prognostic factors for survival of intrahepatic cholangiocarcinoma treated surgically with curative intent. Methods Sixty-seven patients who had been treated surgically for this neoplasm were collected at Bellvitge University Hospital between 1996 and 2017. Epidemiological, clinical, surgical, anatomopathological, morbidity, mortality and survival data have been analysed. Results Postoperative study reflects our centre’s experience in the surgical treatment of intrahepatic cholangiocarcinoma over a period of 21 years. Lymphadenectomy was associated with increased morbidity, and vascular invasion in the pathological study was the most important risk factor in the survival analysis. Conclusions This study reflects our centre's experience in the surgical treatment of intrahepatic cholangiocarcinoma over a period of 21 years. Lymphadenectomy was associated with increased morbidity, and vascular invasion in the pathological study was the most important risk factor in the survival analysis.

Textbook outcome (TBO) is a patient-oriented composite criterion achieved when all desired main health outcomes are realized. The aim was to assess the incidence and the independent factors associated with TBO following LT. This bicentric study included all patients who underwent their first elective liver-only LT between 2011 and 2015. TBO occurred when all the following criteria were fulfilled: no mortality within 90 days, no major complications within 90 days, no reintervention within 90 days (liver graft biopsy, radiological, endoscopic or surgical interventions, or retransplantation), no prolonged intensive care unit stay, and no prolonged hospital stay. Univariable and multivariable analyses were performed to identify factors associated with TBO and to assess whether TBO is an independent factor associated with patient and graft survival. The study population included 530 patients. TBO occurred in 176/530 (33%) patients. Independent factors associated with TBO included the balance of risk score, the use of an intraoperative temporary portacaval shunt, and duration of the operation. TBO was identified as an independent factor associated with graft survival but not patient survival. TBO might be implemented in the patient–doctor decision-making regarding whether to proceed with LT and in the reporting of patient-level hospital performance related to LT.

Liver retransplantation (LRT) is a controversial indication. Our aim was to evaluate the rate of LRT at our institution, and to analyze its indications and short- and long-term results.We conducted a retrospective study of a prospectively collected database, including 1645 LT from 1984 to 2018. Results have been analyzed depending on type of LRT (early vs late), study period and indications.We performed 150 LRT in 140 patients. The LRT rate was 9%. Of these, 45 LRT were early (30%), and the other 70% were late LRT. The main indications were: ischemic cholangitis (27%), arterial thrombosis (19%), primary non-function (15%), and HCV recurrence (15%). Mean surgery duration (395 vs. 270 min; P = .001), cold ischemia time (435 vs. 390 min; P = .005) and transfused units required (8 vs. 5 RBC; P = .034) were higher in cases of late LRT. Postoperative mortality (10 vs. 20%; P = .01) was better in cases of late LRT. One- and 5-year actuarial survival rates were 71% and 58%, respectively, which were significantly better during the last decade (80% and 64%). Five-year actuarial survival for ischemic cholangitis is better than other indications, such as recurrence of HCV (78 vs. 51%; P = .02).Liver retransplantation is complex and associated with high morbidity and mortality. However, indications and long-term results have improved during recent years. Therefore, LRT is justified.

Resumen Introduccion El retrasplante hepatico (ReTH) es una indicacion de TH controvertida. Nuestro objetivo fue determinar la tasa de ReTH y las indicaciones, morbilidad, mortalidad posoperatoria y supervivencia actuarial del paciente retrasplantado en nuestra serie. Metodos Estudio retrospectivo de una serie prospectiva de 1.645 pacientes trasplantados entre 1984 y 2018. Se analizan los resultados segun el tipo de ReTH (precoz vs. tardio), periodo de estudio e indicaciones. Resultados Hemos realizado 150 ReTH en 140 pacientes. La tasa de ReTH fue de 9%. El 30% (45) de los ReTH fueron precoces, siendo tardios el otro 70% (105). Las causas mas frecuentes fueron: colangitis isquemica (27%), trombosis de la arteria hepatica (19%), fallo primario del injerto (15%) y recidiva de la cirrosis por virus de la hepatitis C (VHC) (15%). La duracion de la cirugia (395 vs. 270 min; p = 0,001), tiempo de isquemia (435 vs. 390 min; p = 0,005) y necesidad transfusional (8 vs. 5 CH; p = 0,034) fue mayor en los casos de ReTH tardio, mientras que la mortalidad posoperatoria (10 vs. 20%; p = 0,01) fue mejor en los casos de ReTH tardio. La supervivencia actuarial a uno y cinco anos fue de 71% y 58%, respectivamente, con una mejoria significativa en la ultima decada (80% y 64%). Por otra parte, la supervivencia en los casos de ReTH por colangitis isquemica es superior que otras indicaciones (78 vs. 51%; p = 0,02). Conclusiones El retrasplante es complejo y esta asociado a una elevada morbimortalidad. Sin embargo, los resultados han mejorado en los ultimos anos por lo que su indicacion esta justificada.

Introduction Total pancreatectomy (TP) is an uncommon operation, with indications that have not been clearly defined and non-standardized postoperative results. We present a national multicentric study on TP and a comparison with the existing literature. Methods A prospective observational study using data from the national registry of patients after pancreaticoduodenectomy and TP performed for any indication during the study period: January 1–December 31, 2015. Results 1016 patients were included from 73 hospitals, 112 of whom had undergone TP. The percentage of TP from the total number of cases was 11%. The mean age was 63.5 years, and 57.2% were males. The most frequently suspected radiological diagnosis was pancreatic cancer (58/112 cases). The most common TP technique was “mesentery artery first” (43/112 cases). Venous resections were performed in 23 patients (20.5%). The percentage of postoperative complications within 90 days was 50%, but major complications (>IIIA) were only 20.7%. The overall 90-day mortality was 8% (9 patients). The average stay was 20.7 days. The 3 most frequent definitive histological diagnoses were: adenocarcinoma of the pancreas, intraductal papillary mucinous neoplasm and chronic pancreatitis. The R0 rate was 67.8%. Conclusions This study shows that the morbidity and mortality results of TP in Spain are similar or superior to previous publications. More precise TP studies are necessary, focused on specific complications such as endocrine insufficiency.

Resumen Introduccion La pancreatectomia total (PT) es una intervencion infrecuente, con unas indicaciones no claramente definidas y unos resultados postoperatorios no estandarizados. Presentamos un estudio multicentrico nacional sobre PT y una comparacion con la literatura existente. Metodos Estudio prospectivo observacional realizado mediante el registro nacional de pacientes operados de duodenopancreatectomia cefalica y PT realizadas por cualquier indicacion durante el periodo comprendido entre el 1 enero y el 31 diciembre del 2015. Resultados Se incluyo a 1.016 pacientes, pertenecientes a 73 centros; de ellos, 112 correspondian a PT. El porcentaje de PT/numero total de casos es del 11%. La edad media fue 63,5 anos y eran varones un 57,2%. El diagnostico radiologico de sospecha mas frecuente fue cancer de pancreas (58/112 casos). La tecnica de la PT mas habitual fue «arteria mesenterica primero» (43/112 casos). Se efectuaron resecciones venosas en 23 pacientes (20,5%). El porcentaje de complicaciones postoperatorias a 90 dias fue 50%, pero las complicaciones mayores (> IIIA) solo el 20,7%. La mortalidad global a 90 dias fue del 8% (9 pacientes). La estancia media fue 20,7 dias. Los 3 diagnosticos histologicos definitivos mas frecuentes fueron: adenocarcinoma de pancreas, neoplasia mucinosa papilar intraductal y pancreatitis cronica. La tasa de R0 fue del 67,8%. Conclusiones Este estudio demuestra que los resultados de morbimortalidad de la PT en Espana son similares o superiores a los publicados previamente. Es necesario un estudio mas especifico sobre PT centrado en complicaciones especificas, como la insuficiencia endocrina.

Resumen Introduccion En 2007 se consensuo un protocolo asistencial entre los tres centros de trasplante hepatico (TH) de Cataluna, que contemplaba el trasplante hepatico (TH) asociado a quimiorradioterapia neoadyuvante como tratamiento del colangiocarcinoma perihiliar (CCAp) irresecable. Objetivo Analizar la aplicabilidad del TH en los pacientes con CCAp incluidos en el protocolo y la supervivencia por intencion de tratamiento. Metodos Estudio observacional multicentrico que incluye a pacientes de edad ≤ 68 anos, diagnosticados de CCAp ≤3 cm (diametro radial), irresecable, sin afectacion ganglionar o metastasis a distancia. Los pacientes recibieron tratamiento neoadyuvante basado en radioterapia externa en una dosis total de 45 Gy, asociado con bolos de 5-fluoracilo durante los tres primeros dias de irradiacion y posteriormente capecitabina oral. Aquellos en los que no se objetivo signos de progresion se incluyeron en la lista de espera para TH. Resultados Entre 2007 y 2018, 13 pacientes fueron incluidos en dicho protocolo. Ocho de los 13 pacientes (61%) fueron trasplantados tras un tiempo en lista de espera de 122 dias (rango 5-192). La supervivencia por intencion de tratamiento a 1 y 5 anos fue del 69 y 39%. La supervivencia global post-TH a 1 y 5 anos fue del 87 y 62%, con una probabilidad de recidiva del 29% a los cinco anos post-TH. Conclusion La aplicabilidad del trasplante hepatico combinado con quimiorradioterapia neoadyuvante ha sido del 61% en nuestra serie y debe ser considerado como un tratamiento potencialmente curativo para pacientes seleccionados con CCAp irresecable y sin enfermedad metastasica.

Introduction Chronic pain in chronic pancreatitis is difficult to manage. The objective of our study is to assess the control of pain that is refractory to medical treatment in patients with an inflammatory mass in the head of the pancreas, as well as to compare the two surgical techniques. Methods A retrospective study included patients treated surgically between 1989 and 2011 who had been refractory to medical treatment with inflammation of the head of the pancreas. An analysis of the short and long-term results was done to compare patients who had undergone pancreaticoduodenectomy (PD) and/or resection of the head of the pancreas with duodenal preservation (RHPDP). Results 22 PD and 12 RHPDP were performed. Postoperative complications were observed in 14% of patients, the most frequent being delayed gastric emptying (14.7%) and pancreatic fistula (11.7%). No statistically significant differences were found in terms of surgical technique. Pain control was satisfactory in 85% of patients, 43% presented de novo diabetes mellitus, and 88% returned to their work activities. Fourteen patients died during follow-up, 7 due to malignancies, and some were related to tobacco use and alcohol consumption. The overall 5 and 10 year survival rates were 88% and 75% respectively. Conclusion Cephalic resection in patients with intractable pain in chronic pancreatitis is an effective therapy that provides good long-term results in terms of pain control, with no significant differences between the two surgical techniques. Patients with chronic pancreatitis have a high mortality rate associated with de novo malignancies.

Resumen Introduccion El dolor cronico en la pancreatitis cronica es de dificil manejo. El objetivo de nuestro trabajo es la valoracion del control del dolor refractario al tratamiento medico en pacientes afectos de masa inflamatoria en la cabeza pancreatica, asi como comparar dos tecnicas quirurgicas realizadas. Metodos Estudio retrospectivo sobre pacientes intervenidos entre 1989 y 2011 refractarios al tratamiento medico con predominio inflamatorio en la cabeza pancreatica. Se realizo un estudio comparativo a corto y a largo plazo entre los pacientes intervenidos mediante duodenopancreatectomia cefalica (DPC) y/o pancreatectomia cefalica con preservacion duodenal (PCPD). Resultados Se realizaron 22 DPC y 12 PCPD. En el 44% de los casos se presentaron complicaciones posquirurgicas, siendo las mas frecuentes el vaciamiento gastrico retardado (14,7%) y la fistula pancreatica (11,7%). No se evidenciaron diferencias estadisticamente significativas segun la tecnica quirurgica. Se consiguio el control del dolor de forma satisfactoria en el 85% de los pacientes, hubo un 43% de diabetes mellitus de novo, y la reincorporacion a la actividad laboral fue del 88%. Catorce pacientes fallecieron durante el seguimiento; de ellos, 7 a causa de neoplasias, algunas de ellas relacionadas con el consumo de tabaco y alcohol. La supervivencia global a 5 y 10 anos fue del 88 y del 75%, respectivamente. Conclusion La reseccion cefalica en pacientes con dolor intratable en la pancreatitis cronica es una terapeutica eficaz, con buenos resultados a largo plazo en terminos de control del dolor y sin diferencias significativas entre ambas tecnicas quirurgicas. Los pacientes con pancreatitis cronica presentan una elevada mortalidad asociada a neoplasias de novo.

Introduction: The access of surgeons to liver transplant teams in Spain is heterogeneous. This study aims to portray the current human resources of Spanish transplant teams, distribution of transplant duties among team members, how transplant team members acquire their skills, their leaders' view of their future, as well the motivations of Spanish General Surgery residents to choose transplantation as their future career choice. Methods: Two different surveys were created, one for head surgeons and one for residents, about the number of team members and their training, recruitment, organization of tasks and motivation to work in transplantation. The questionnaires were e-mailed to both the transplant program directors and the surgical residents. Results: There are on average 8 surgeons in each transplant unit. More than four surgeons perform the hepatectomy in 54.2% of the groups, while the graft implantation is performed by more than 4 surgeons at just 25% of the centers. Forty-two percent of the transplant chiefs advocated a fellowship training system, and 87.5% believe that generational turnover is guaranteed. Out of 525 residents, 101 responded. Regarding training, 12.8% had no interest in transplantation. Concerning their work preferences, 37.6% were not interested in transplantation because it is excessively demanding, and 52.5% would not like to be part of a liver transplant team in the future. Conclusions: The generational turnover seems to be guaranteed according to liver transplant program directors. The new generations of surgeons generally opt for other areas of surgery other than transplantation. Studies with a greater number of responses are necessary to validate these results (C) 2019 AEC. Published by Elsevier Espana, S.L.U. All rights reserved.

Resumen Introduccion El acceso de los cirujanos a los equipos de trasplante hepatico en Espana se realiza de manera heterogenea. El objetivo de este estudio ha sido cuantificar los recursos humanos de los equipos de trasplante espanoles, la distribucion de las diferentes tareas del trasplante entre los miembros del equipo, el mecanismo mediante el cual se adquieren las habilidades, la vision de sus lideres sobre su continuidad, asi como las motivaciones de los residentes de cirugia general espanoles para elegir el trasplante como su futura carrera profesional. Metodos Se elaboraron dos encuestas diferentes, para los jefes de equipo y para residentes, sobre numero de personas, capacitacion, reclutamiento, organizacion de tareas y motivacion para trabajar en trasplantes. Los cuestionarios se enviaron por correo electronico tanto a los directores de programa de trasplante como a los residentes de cirugia. Resultados Hay en promedio 8 cirujanos en cada unidad de trasplante. Mas de 4 cirujanos realizan la hepatectomia en el 54,2% de los grupos, mientras que el implante lo realiza mas de 4 cirujanos en solo el 25% de los centros. El 42% de los jefes de trasplante hepatico aboga por un sistema tipo fellowship y el 87,5% cree que el recambio generacional esta garantizado. De los 525 residentes, 101 respondieron. Respecto a la formacion, un 12,8% no tiene interes en el trasplante. En cuanto a sus preferencias laborales, el 37,6% no esta interesado en el trasplante por ser excesivamente exigente, y el 52,5% no desea ser parte de un equipo de trasplante de higado en el futuro. Conclusiones El recambio generacional parece estar garantizado segun los directores de programa de trasplante de higado. Las nuevas generaciones de cirujanos generalmente optan por otras areas de cirugia diferentes al trasplante. Son necesarios estudios con mayor numero de respuestas para validar estos resultados.

Several techniques have been proposed for liver transplantation with inadequate hepatic artery (HA) anastomosis. We aimed to analyze outcomes of arterial reconstruction with the splenic artery (SA). This was a prospective study of our experience with recipients who underwent arterial anastomosis on the SA compared with patients who underwent standard HA. We included 54 patients in the SA group and 1405 in the HA group. Patients in SA group were more frequently retransplantation (31% vs. 8%; P = 0.001), required more transfusion (11 ± 12 vs. 6 ± 9.9 PRC; P = 0.001), had longer surgeries (424 ± 95 vs. 394 ± 102 min; P = 0.03), and longer hospital stays (28 ± 29 vs. 20 ± 18 days; P = 0.002). There were no differences in vascular and biliary complications (15% and 7%; P = 0.18; and 32% and 23%; P = 0.32), primary dysfunction (11% and 9%; P = 0.74), reoperation (12% and 10%; P = 0.61), postoperative mortality (13% and 7%; P = 0.12) and 5 years survival (66% vs. 63%; P = 0.71). Following primary transplantation, there were no differences. The outcomes of arterial reconstruction using the recipients' SA in adult liver transplantation are comparable to those for standard HA reconstruction after a first transplant.

Objective To define technically difficult liver transplantation (Diff-LT). Summary background data Currently, there is no acknowledged definition of Diff-LT. Methods This retrospective study included all first consecutive liver-only transplantations performed in two centers from 2011 to 2015. Diff-LT was defined as the combination of the number of blood units transfused, cold ischemia time, and duration of operation, all at or above the median value of the entire population. The correlation of Diff-LT with short- (including the comprehensive complication index [CCI]) and long-term outcomes was assessed. Outcomes were also compared to the 90-day benchmark cutoffs of LT. Predictors of Diff-LT were identified by multivariable analysis, first using only recipient data and then using all recipient, donor, graft, and surgical data. Results The study population included 467 patients. The incidence of Diff-LT was 18.8%. Diff-LT was associated with short-term outcomes, including the CCI and mortality, but not with patient or graft long-term survival. Previous abdominal surgery, intensive care unit-bound at the time of LT, split graft use, non-standard arterial reconstruction, and porto-systemic shunt ligation were independent predictors of Diff-LT. The proportion of variables below the corresponding LT 90-day benchmark cutoffs was 8/13 (61.5%) for non-Diff-LT, and 4/13 (30.8%) for Diff-LT. Conclusions Diff-LT, as defined, occurred frequently. Adjusting modifiable variables might decrease the risk of Diff-LT and improve the postoperative course. This definition of Diff-LT might be useful for patient information, comparison between centers and surgeons, and as a metric in future trials.

Objective To evaluate the short- and long-term outcomes of renoportal anastomosis (RPA) in a large multicentric series. Summary background The current knowledge on RPA for portal reconstruction during liver transplantation (LT) in patients with diffuse portal vein thrombosis (PVT) and a large splenorenal shunt (SRS) is poor and limited to case reports and small case series. Methods All consecutive LTs with RPA performed in 5 centers between 1998 and 2020 were included. RPA was physiological provided it drained the splanchnic venous return through a large SRS (≥1 cm diameter). Complications of portal hypertension (PHT), long-term RPA patency, and patient and graft survival were assessed. RPA success was achieved provided the 3 following criteria were all fulfilled: patients were alive with patent RPA and without clinical PHT. Results RPA was attempted and feasible in 57 consecutive patients and was physiological in 51 patients (89.5%). Ninety-day mortality occurred in 5 (8.5%) patients, and PHT-related complications occurred in 42.9% of patients. With a median follow-up of 63 months, the 1-, 3- and 5-year patient and graft survival rates were 87%, 83%, and 76% and 82%, 80%, and 73%, respectively. The primary and primary-assisted patency rates at 5 years were 84.5% and 94.3%, respectively. Success was achieved in 90% (27/30) of patients with a follow-up ≥ 5 years. Conclusions Despite a high rate of PHT-related complications, excellent long-term patient and graft survival could be achieved. RPA could be considered successful in the vast majority of patients. The expanded use of RPA is warranted.

International audience; Transplant and patient survival are the validated endpoints to assess the success of liver transplantation (LT). This study evaluates arterial and biliary complication-free survival (ABCFS) as a new metric. ABC, considered as an event, was an arterial or biliary complication of Dindo-Clavien grade ≥III complication dated at the interventional, endoscopic, or surgical treatment required to correct it. ABCFS was defined as the time from the date of LT to the dates of first ABC, death, relisting, or last follow-up (transplant survival is time from LT to repeat LT or death). Following primary whole LT (n = 532), 106 ABCs occurred and 99 (93%) occurred during the first year after LT. An ABC occurring during the first year after LT (overall rate 19%) was an independent factor associated with transplant survival (hazard ratio [HR], 3.17; P < 0.001) and patient survival (HR, 2.7; P = 0.002) in univariate and multivariate analyses. This result was confirmed after extension of the cohort to splitliver graft, donation after circulatory death, or re-LT (n = 658). Data from 2 external cohorts of primary whole LTs (n = 249 and 229, respectively) confirmed that the first-year ABC was an independent prognostic factor for transplant survival but not for patient survival. ABCFS was correlated with transplant and patient survival (ρ = 0.85 [95% CI, 0.78-0.90] and 0.81 [95% CI, 0.71-0.88], respectively). Preoperative factors known to influence 5-year transplant survival influenced ABCFS after 1 year of follow-up. The 1-year ABCFS was indicative of 5-year transplant survival. ABCFS is a reproducible metric to evaluate the results of LT after 1 year of follow-up and could serve as a new endpoint in clinical trials.

Background Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils (i.e. amyloid). Apart from the common Val30Met mutation there is a very heterogeneous group of non-Val30Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results Three patients needed a staged (1 patient) or simultaneous (2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac (allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions This is the first report in (liver) transplant literature about the rare Val122del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.

BACKGROUND Delaying initiation of tacrolimus after liver transplantation (LT) is a potential renal-sparing strategy. We assessed safety and efficacy of delayed initiation of prolonged-release tacrolimus (PR-T) in de novo LT. MATERIAL AND METHODS This was a single-center, single-arm, prospective, 12-month observational study of hepatitis C virus-negative orthotopic LT patients. Immunosuppression included PR-T (initially 0.1 or 0.2 mg/kg/day) initiated on Day 3 post LT, basiliximab (20 mg) on post-transplantation Day 0 and Day 4, and intraoperative corticosteroids (500 mg). Patients received maintenance corticosteroids and mycophenolate mofetil (MMF) according to center protocol. MMF dose was adjusted according to thrombocyte count. The primary endpoint was the estimated glomerular filtration rate (eGFR) measured using the Modification of Diet in Renal Disease 4-variable formula at 12 months. Secondary endpoints included biopsy-confirmed acute rejection (BCAR) and dialysis requirement. Adverse events were recorded. RESULTS Sixty-nine patients (mean age 55.0 years) were included. Most patients started MMF on Day 1 (60.9%) or Day 2 (10.1%), and PR-T on Day 3 (55.1%) or Day 4 (29.0%). Mean tacrolimus trough levels (ng/mL) were: Day 7, 9.5±6.3; Day 10, 9.4±5.4; Month 1, 8.0±3.1; Month 3, 7.8±3.7; Month 6, 8.0±4.1; and Month 12, 7.2±3.1. Mean 12-month eGFR was 77.2±24.5 mL/min/1.73 m2; 72.5% of patients had eGFR >60 mL/min/1.73 m² at 12 months; 89.9% had no eGFR measurements

OBJECTIVE: To use the concept of benchmarking to establish robust and standardized outcome references after pancreatico-duodenectomy (PD). BACKGROUND: Best achievable results after PD are unknown. Consequently, outcome comparisons among different cohorts, centers or with novel surgical techniques remain speculative. METHODS: This multicenter study analyzes consecutive patients (2012-2015) undergoing PD in 23 international expert centers in pancreas surgery. Outcomes in patients without significant comorbidities and major vascular resection (benchmark cases) were analyzed to establish 20 outcome benchmarks for PD. These benchmarks were tested in a cohort with a poorer preoperative physical status (ASA class ≥3) and a cohort treated by minimally invasive approaches. RESULTS: Two thousand three hundred seventy-five (38%) low-risk cases out of a total of 6186 PDs were analyzed, disclosing low in-hospital mortality (≤1.6%) but high morbidity, with a 73% benchmark morbidity rate cumulated within 6 months following surgery. Benchmark cutoffs for pancreatic fistulas (B-C), severe complications (≥ grade 3), and failure-to-rescue rate were 19%, 30%, and 9%, respectively. The ASA ≥3 cohort showed comparable morbidity but a higher in hospital-mortality (3% vs 1.6%) and failure-to-rescue rate (16% vs 9%) than the benchmarks. The proportion of benchmark cases performed varied greatly across centers and continents for both open (9%-93%) and minimally invasive (11%-62%) PD. Centers operating mostly on complex PD cases disclosed better results than those with a majority of low-risk cases. CONCLUSION: The proposed outcome benchmarks for PD, established in a large-scale international patient cohort and tested in 2 different cohorts, may allow for meaningful comparisons between different patient cohorts, centers, countries, and surgical techniques.

Background Delayed gastric emptying (DGE) is the most important cause of an extended hospital stay after pancreatoduodenectomy. Reports suggest that a Roux-en-Y gastroenteric anastomosis may have lower incidence of DGE than a Billroth II reconstruction. The primary aim of this RCT was to compare Billroth II (single loop) and Roux-en-Y (double loop) after pancreatoduodenectomy to determine whether Roux-en-Y reconstruction is associated with a lower incidence of DGE. Secondary endpoints were postoperative complications. Methods This was a randomized unblinded single-centre trial without masked evaluation of the main outcome. Patients undergoing pancreatoduodenectomy between 2013 and 2015 were randomized to undergo one of two types of gastroenteric anastomosis for reconstruction. Results A total of 80 patients were randomized, 40 in each group. The incidence of DGE was the same in patients undergoing Billroth II or Roux-en-Y gastroenteric anastomosis (both 18 of 40 patients; P = 1·000). The grade of DGE was also similar in the Billroth II and Roux-en-Y groups (grade A, both 10 of 40; grade B, 5 of 40 versus 6 of 40; grade C, 3 of 40 versus 2 of 40; P = 0·962). The mortality rate was 3 per cent, with no significant difference between the two groups. There were no differences in the overall rate of postoperative morbidity, relaparotomy rate or duration of hospital stay. Conclusion The incidence and severity of DGE does not differ between single- or double-loop gastroenteric anastomosis performed after pancreatoduodenectomy. Registration number: NCT00915863 (http://www.clinicaltrials.gov).

BackgroundNeoadjuvant therapy (NAT) for pancreatic adenocarcinoma (PDAC) patients has shown promising results in non-randomized trials. This is a multi-institutional phase II trial of NAT in resectable PDAC patients.MethodsPatients with confirmed resectable PDAC after agreement by two expert radiologists were eligible. Patients received three cycles of GEM (1000mg/m(2)/week) plus daily erlotinib (ERL) (100mg/day). After re-staging, patients without progressive disease underwent 5 weeks of therapy with GEM (300mg/m(2)/week), ERL 100mg/day and concomitant radiotherapy (45Gy). Efficacy was assessed using tumor regression grade (TRG) and resection margin status. Using a single-arm Simon's design, considering the therapy not useful if R070% (alpha 5%, beta 10%), 24 patients needed to be recruited. This trial was registered at ClinicalTrials.gov, number NCT01389440.ResultsTwenty-five patients were enrolled. Adverse effects of NAT were mainly mild gastrointestinal disorders. Resectability rate was 76%, with a R0 rate of 63.1% among the resected patients. Median overall survival (OS) and disease-free survival (DFS) were 23.8 (95% CI 11.4-36.2) and 12.8 months (95% CI 8.6-17.1), respectively. R0 resection patients had better median OS, compared with patients with R1 resection or not resected (65.5 months vs. 15.5 months, p=0.01). N0 rate among the resected patients was 63.1%, and showed a longer median OS (65.5 vs. 15.2 months, p=0.009).ConclusionThe results of this study confirm promising oncologic results with NAT for patients with resectable PDAC. Therefore, the present trial supports the development of phase II randomized trials comparing NAT vs. upfront surgery in resectable pancreatic cancer.

The aim of this study was to evaluate whether the placement of a coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent (LAMS) may improve the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs).This was a retrospective cohort study including patients with PFCs and an indication for transmural drainage. Two strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist's discretion.A total of 41 patients were treated (21 LAMS alone; 20 LAMS plus DPS). The characteristics of the PFCs, and the technical and clinical success rates did not differ between groups. The LAMS alone group had a significantly higher rate of adverse events than the LAMS plus DPS group (42.9 % vs. 10.0 %;The addition of a coaxial DPS to LAMS was associated with a lower rate of adverse events in EUS-guided drainage of PFCs.The aim of this study was to evaluate whether the placement of a coaxial double-pigtail plastic stent (DPS) within a lumen-apposing metal stent (LAMS) may improve the safety of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs).This was a retrospective cohort study including patients with PFCs and an indication for transmural drainage. Two strategies (LAMS alone or LAMS plus DPS) were used at the endoscopist’s discretion.A total of 41 patients were treated (21 LAMS alone; 20 LAMS plus DPS). The characteristics of the PFCs, and the technical and clinical success rates did not differ between groups. The LAMS alone group had a significantly higher rate of adverse events than the LAMS plus DPS group (42.9 % vs. 10.0 %;The addition of a coaxial DPS to LAMS was associated with a lower rate of adverse events in EUS-guided drainage of PFCs.

Introduction The need for fluoroscopy guidance in patients undergoing endoscopic ultrasound-guided transmural drainage (EUS-TMD) of peripancreatic fluid collections (PFCs) remains unclear. Aims The aim of this study was to compare general outcomes of EUS-TMD of PFCs under fluoroscopy (F) vs fluoroless (FL). Methods This is a comparative study with a retrospective analysis of a prospective and consecutive inclusion database at a tertiary centre, from 2009 to 2015. All patients were symptomatic pseudocyst (PSC) and walled-off pancreatic necrosis (WON). Two groups were assigned depending on availability of fluoroscopy. The groups were heterogeneous in terms of their demographic characteristics, PFCs and procedure. The main outcome measures included technical and clinical success, incidences, adverse events (AEs), and follow-up. Results Fifty EUS-TMD of PFCs from 86 EUS-guided drainages were included during the study period. Group F included 26 procedures, PSC 69.2%, WON 30.8%, metal stents 61.5% (46.1% lumen-apposing stent) and plastic stents 38.5%. Group FL included 24 procedures, PSC 37.5%, WON 62.5%, and metal stents 95.8% (lumen-apposing stents). Technical success was 100% in both groups, and clinical success was similar (F 88.5%, FL 87.5%). Technical incidences and intra-procedure AEs were only described in group F (7.6% and 11.5%, respectively) and none in group FL. Procedure time was less in group FL (8 min, p = 0.0341). Conclusions Fluoroless in the EUS-TMD of PFCs does not involve more technical incidences or intra-procedure AEs. Technical and clinical success was similar in the two groups.

A survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (< 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country. Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95 %: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95 %: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95 %: 7,6-13,3; rango, 2-33). Solo el 41,2 % de los grupos utilizaban soporte nutricional antes de la cirugía (< 50 % habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4 % habían intentado administrar una dieta oral precoz, pero el 88,2 % de los grupos usaron algún tipo de soporte nutricional y el 26,5 % usaron NP en el 100 % de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6 % utilizaron NP siempre y NE en el 19,3 % de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4 % de las unidades usan nutrición oral precoz y el 32,3 % emplean la NE tras este tipo de cirugía. El 22,6 % de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación.

Liver transplantation (LT) after neoadjuvant chemoradiotherapy in patients with unresectable hilar cholangiocarcinoma (HC) is an accepted treatment strategy [1]. Neoadjuvant therapy is associated with an increased risk of arterial and portal complications after LT [1,2]. In most cases, radiation therapy makes the use of the native hepatic artery inadvisable, and an aortic anastomosis is needed, either with or without a graft [2]. The development of a mycotic pseudoaneurysm after LT is a rare complication that is associated with a high incidence of graft failure and mortality. Radiotherapy, local infections and the use of grafts are known risk factors for the development of a mycotic pseudoaneurysm, which is always challenging to manage [3].

Background and aim Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. Material and methods A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher’s exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. Results RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). Conclusion RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.

MicroRNAs from the miR-200 family are commonly associated with the inhibition of the metastatic potential of cancer cells, following inhibition of ZEB transcription factors expression and epithelial-to-mesenchymal transition. However, previous studies performed in pancreatic adenocarcinoma revealed a more complex picture challenging this canonical model. To gain better insights into the role of miR-200 family members in this disease, we analyzed the expression of miR-200a, miR-200b, miR-200c, miR-141, miR-429, and miR-205, and ZEB1, ZEB2, and CDH1 in pancreatic tumors and matching normal adjacent parenchyma and patient-derived xenografts. We found that miR-200a, miR-429, and miR-205 are frequently overexpressed in pancreatic tumors, whereas CDH1 is downregulated, and ZEB1 and ZEB2 levels remain unchanged. Furthermore, we measured a positive correlation between miR-200 family members and CDH1 expression, and a negative correlation between ZEB1 and miR-200c, miR-141, and miR-205 expression, respectively. Interestingly, we identified significant changes in expression of epithelial-to-mesenchymal transition regulators and miR-200 members in patient-derived xenografts. Lastly, functional studies revealed that miR-141 and miR-429 inhibit the tumorigenic potential of pancreatic cancer cells. Taken together, this comprehensive analysis strongly suggests that miRNAs from the miR-200 family, and in particular miR-429, may act as a tumor suppressor gene in pancreatic cancer. Keywords: pancreatic cancer, patient-derived xenograft, miR-200 family, miR-429

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.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.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 Ki675%. 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.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.

Resumen Objetivo La disponibilidad de nuevas tecnicas de imagen ha condicionado un incremento en el diagnostico incidental de pequenos tumores neuroendocrinos pancreaticos 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 evolucion de TNP-NF incidentales de pequeno tamano, tratados con seguimiento clinico sin cirugia. Metodos Se realizo un analisis 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 asintomaticos. El diagnostico se realizo mediante pruebas de imagen, indicando ecoendoscopia-puncion en caso de dudas diagnosticas. El seguimiento se hizo en nuestro centro, con registro de cambios clinicos y radiologicos. Resultados Incluimos a 24 pacientes con una mediana de edad de 70 anos y distribucion similar en cuanto al sexo. El diagnostico se realizo mediante tomografia computarizada multidetector, resonancia nuclear magnetica y gammagrafia con octreotide. Los tumores se localizaban principalmente en cabeza y cuello (46%), con un tamano medio de 11,5 ± 3,55 mm al diagnostico (5-19 mm). En 2 casos se asocio ecoendoscopia-puncion (8%), confirmando el diagnostico de TNP de bajo grado con Ki67 Conclusion En pacientes seleccionados, el manejo no quirurgico de TNP-NF, asintomaticos y ≤2 cm es una opcion a tener en cuenta. Son necesarios estudios con mayor numero de pacientes y un seguimiento mayor para validar esta opcion conservadora.

Resumen Introduccion La duodenopancreatectomia cefalica (DPC) es el tratamiento de eleccion de los tumores del area periampular. Esta intervencion presenta una elevada morbilidad postoperatoria, y suele estar contraindicada en los pacientes con hepatopatia cronica (CH). Analizar los resultados de la DPC en pacientes cirroticos, y compararlos con los de pacientes no cirroticos. Metodos Entre abril de 1994 y noviembre de 2014 registramos de forma prospectiva a todos los pacientes a los que se les realizo una DPC por cancer del area periampular en el Hospital Universitari de Bellvitge. Se recogieron de forma prospectiva variables preoperatorias, intraoperatorias y del postoperatorio inmediato. Se definio grupo de estudio a los pacientes tratados mediante DPC y afectos de cirrosis hepatica (grupo CH), y grupo control a pacientes intervenidos sin cirrosis hepatica (grupo NCH); se realizo un estudio caso/control (1/2). Resultados Registramos a 15 pacientes del grupo CH, todos ellos con una buena funcion hepatica (Child A), y a 30 del grupo NCH. La causa de la hepatopatia fue VHC (60%) y enolismo (40%). En los 3 instantes estudiados, los pacientes del grupo CH presentaron una cifra de plaquetas en sangre inferior y una ratio de protrombina superior, respecto al grupo NCH. La morbilidad postoperatoria fue del 60%, con una estancia media de 25 ± 19 dias; sin diferencias significativas en la incidencia de complicaciones entre el grupo CH y NCH (73 vs. 53%; p = 0,1). La presencia de ascitis durante el postoperatorio fue superior en el grupo CH respecto al NCH (28 vs. 0%; p Conclusiones La DPC es una intervencion segura entre los pacientes hepatopatas con buena funcion hepatica preoperatoria, a pesar de comportar una elevada morbilidad.