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Several organ allocation protocols give priority to wait-listed simultaneous kidney-pancreas (SPK) transplant recipients to mitigate the higher cardiovascular risk of patients with diabetes mellitus on dialysis. The available information regarding the impact of preemptive simultaneous kidney-pancreas transplantation on recipient and graft outcomes is nonetheless controversial. To help resolve this, we explored the influence of preemptive simultaneous kidney-pancreas transplants on patient and graft survival through a retrospective analysis of the OPTN/UNOS database, encompassing 9690 simultaneous transplant recipients between 2000 and 2017. Statistical analysis was performed applying a propensity score analysis to minimize bias. Of these patients, 1796 (19%) were transplanted preemptively. At ten years, recipient survival was significantly superior in the preemptive group when compared to the non-preemptive group (78.9% vs 71.8%). Dialysis at simultaneous kidney-pancreas transplantation was an independent significant risk for patient survival (hazard ratio 1.66 [95% confidence interval 1.32-2.09]), especially if the dialysis duration was 12 months or longer. Preemptive transplantation was also associated with significant superior kidney graft survival compared to those on dialysis (death-censored: 84.3% vs 75.4%, respectively; estimated half-life of 38.57 [38.33 -38.81] vs 22.35 [22.17 - 22.53] years, respectively). No differences were observed between both groups neither for pancreas graft survival nor for post-transplant surgical complications. Thus, our results sustain the relevance of early referral for pancreas transplantation and the importance of pancreas allocation priority in reducing patient mortality after simultaneous kidney-pancreas transplantation.

Pancreas transplantation is, at present, the only curative treatment for type-1 diabetes that maintains normoglycemia thus avoiding complications arising from poor glycemic control. Despite its great benefits, the number of pancreas transplants has decreased significantly since its inception in the late 1960s, largely due to demographic changes and the consequent suboptimal quality of donors. The selection criteria for pancreas donors mainly depend on morphological variables such as fatty infiltration, fibrosis, or edema, as well as both functional (amylase and lipase) and clinical variables of the donor. However, the final criterion in the decision-making process is the somewhat subjective assessment of a trained surgeon. That being said, the recent incorporation of graft perfusion machines into clinical practice seems to be changing the work dynamics of the donor organ retrieval team, facilitating decision-making based on objective morphological and functional criteria. Normothermic perfusion using perfusate with supplemental oxygen replicates near physiological parameters thus being a promising strategy for organ preservation. Nevertheless, optimum perfusion parameters are difficult to establish in pancreas transplantation given its complex vascular anatomy combined with an intrinsically low blood flow. The objective of this work is to analyze the results published in the recent literature relating to the considerations of ex-vivo normothermic graft perfusion machines and their usefulness in the field of pancreas transplantation.

The European Society for Organ Transplantation (ESOT) has created a platform for the development of rigorous and regularly updated evidence based guidelines for clinical practice in the transplantation field. A dedicated Guideline Taskforce, including ESOT-council members, a representative from the Centre for Evidence in Transplantation, editors of the journal Transplant International has developed transparent procedures to guide the development of guidelines, recommendations, and consensus statements. During ESOT's first Consensus Conference in November 2022, leading experts will present in-depth evidence based reviews of nine themes and will propose recommendations aimed at reaching a consensus after public discussion and assessment by an independent jury. All recommendations and consensus statements produced for the nine selected topics will be published including the entire evidence-based consensus-finding process. An extensive literature review of each topic was conducted to provide final evidence and/or expert opinion.

Information about the impact of diabetic neuropathy (DN) on outcomes after pancreas transplantation (PT) is scarce. We assessed the independent relationship between DN markers with both graft survival and incident cardiovascular disease (CVD) after transplantation.A cohort study in individuals with type 1 diabetes and end-stage kidney disease who underwent PT between 1999 and 2015 was conducted. DN was assessed with vibration perception thresholds (VPTs) and orthostatic hypotension (pre-PT and 6 mo, 2-3, 5-6, and 8-10 y after transplantation). Pretransplantation and posttransplantation DN markers were related with graft failure/dysfunction and incident CVD during follow-up.We included 187 participants (70% men, age 39.9 ± 7.1 y, diabetes duration 27.1 y), with a median follow-up of 11.3 y. Abnormal VPTs (≥25 V) were observed in 53%. After transplantation, VPTs improved (22.4 ± 8.4 pretransplant versus 16.1 ± 6.1 V at 8-10 y post-PT; P0.001); additionally, the prevalence of abnormal VPTs decreased (53% pretransplant versus 24.4% at 8-10 y; P0.001). After adjusting for age, sex, diabetes duration, blood pressure, body mass index, and previous CVD, pretransplant VPTs ≥25 V were independently associated with pancreas graft failure/dysfunction (hazard ratio [HR], 2.01 [1.01-4.00]) and incident CVD (HR, 2.57 [1.17-5.64]). Furthermore, persistent abnormal VPTs after 6 mo posttransplantation were associated with the worst outcomes (HR, 2.80 [1.25-6.23] and HR, 3.19 [1.14-8.96], for graft failure/dysfunction and incident CVD, respectively).In individuals with type 1 diabetes and end-stage kidney disease, PT was associated with an improvement of VPTs. This simple and widely available DN study was independently associated with pancreas graft function and CVD posttransplantation.

Introduction The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour

BACKGROUND AND AIMS The evidence regarding the benefits of performing preemptive SPK (pSPK) is controversial. The aim of the present study was to evaluate the impact of pSPK on long-term patient and grafts outcomes when compared with npSPK and pKTA through a national registry study with recipients reported to the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) registry, and to analyse the potential benefits associated with pSPK not only in patients with T1D but also in patients with T2D. METHOD To explore the survival advantage of performing a pSPK, we compared the outcomes in pSPK with nonpreemptive SPK (npSPK) recipients between 2000 and 2017 from the OPTN/UNOS registry. To account for the potential benefit provided solely by the kidney transplant, we further compared to recipients of preemptive Kidney Transplantation Alone (pKTA) with diabetes. A propensity score analysis was applied. RESULTS A total of 1522 patients received a pSPK, 7894 an npSPK and 3343 a pKTA. Overall recipient survival was superior for the pSPK group when compared with the pKTA (97.7%, and 80.9% versus 97.7% and 72.9% at 1 and 10 years, respectively, P CONCLUSION In conclusion, the observed survival benefit of performing an SPK preemptively reinforces the need for early referral for transplantation in patients with insulin-dependent diabetes and advanced chronic kidney disease.

BACKGROUND AND AIMS ‘Stress hyperglycaemia’ is a condition characterized by elevated blood glucose levels during stress or illness. It is often multifactorial and leads to transient insulin resistance and/or insulin deficiency in critical ill patients. Patients with stress hyperglycaemia could be potential pancreas donors, although there is some concern about the influence of donor insulin use on pancreas graft survival. Studies have reported that stress hyperglycaemia increases the risk toward the development of type 2 diabetes (T2D) on the long term, but the patient profiles were of those not usually considered for pancreas donation. The objective of our study was to assess the impact of insulin requirements during intensive care unit (ICU) in surviving patients who otherwise would be potentially eligible for pancreas donation. The risk of T2D at 3 years after discharge was assessed to understand the pancreas function recovery after stress hyperglycaemia. METHOD we developed a retrospective study including patients admitted in the ICU between March 2011 and December 2017 due to severe neurological acute conditions [subarachnoid haemorrhage (SAH), head trauma, non-SAH haemorrhage or stroke]. Inclusion criteria were as follows: severe neurological condition requiring need for intubation, age RESULTS A total of 76 patients were included, with insulin requirement during ICU admission reported in only 5 (6.6%). Median age was 45 years (IQR 35–52), 50% were males, median Charlson index was 0, and 25 (32.9%) had present or past smoking habit. Hypertension was present in 11 (14.5%) and dyslipidaemia in 7 (9.2%). The main admission cause was SAH in 45 patients (59.2%) followed by head trauma in 21 (27.6%). As for hyperglycaemic factors, during admission, 6 (7.9%) received parenteral nutrition, 48 (63%) had an infectious complication, 51 (67%) received corticosteroids and 49 (64.5%) were under propofol sedation. A total of 55 (72.4%) received noradrenaline. Median amylase, lipase, AST and ALT peak were 115 U/L (69.5–233), 70 U/L (34–222), 51 U/L (33.25–101.5) and 94 U/L (35.5–165), respectively. Median ICU and hospital stay were 10 (5–17.75) and 29 (19–42.75) days, respectively. Those who required insulin had longer ICU stay compared with the median of the overall cohort (25 versus 10 days); all of them received corticosteroids and were diagnosed with SAH. At 3 years of follow-up, only three patients (3.9%) were diagnosed with T2D, but none of them had received insulin during admission. One patient was diagnosed 7 months after discharge and the other two were diagnosed 1 year after discharge. Three patients died during the follow-up, but any of them also required insulin during admission. CONCLUSION Insulin requirement in patients with severe neurological acute conditions who could meet criteria for pancreas donation was less common than expected, despite large use of corticoids, infectious complications and propofol sedation as hyperglycaemic factors. Remarkably, only three patients were diagnosed of T2D during the follow-up and none of them received insulin during admission. Prospective studies are needed in order to understand pancreas recovery after stress hyperglycaemia.

Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients’ experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient’s perspective will consolidate our program and may add new prototype service design components.

The aim of this minireview is to compare various pancreas transplantation exocrine drainage techniques i.e., bladder vs enteric. Both techniques have different difficulties and complications. Numerous comparisons have been made in the literature between exocrine drainage techniques throughout the history of pancreas transplantation, detailing complications and their impact on graft and patient survival. Specific emphasis has been made on the early postoperative management of these complications and the related surgical infections and their consequences. In light of the results, a number of bladder-drained pancreas grafts required conversion to enteric drainage. As a result of technical improvements, outcomes of the varied enteric exocrine drainage techniques (duodenojejunostomy, duodenoduodenostomy or gastric drainage) have also been discussed i.e., assessing specific risks vs benefits. Pancreatic exocrine secretions can be drained to the urinary or intestinal tracts. Until the late 1990s the bladder drainage technique was used in the majority of transplant centers due to ease of monitoring urine amylase and lipase levels for evaluation of possible rejection. Moreover, bladder drainage was associated at that time with fewer surgical complications, which in contrast to enteric drainage, could be managed with conservative therapies. Nowadays, the most commonly used technique for proper driving of exocrine pancreatic secretions is enteric drainage due to the high rate of urological and metabolic complications associated with bladder drainage. Of note, 10% to 40% of bladder-drained pancreata eventually required enteric conversion at no detriment to overall graft survival. Various surgical techniques were originally described using the small bowel for enteric anastomosis with Roux-en-Y loop or a direct side-to-side anastomosis. Despite the improvements in surgery, enteric drainage complication rates ranging from 2%-20% have been reported. Treatment depends on the presence of any associated complications and the condition of the patient. Intra-abdominal infection represents a potentially very serious problem. Up to 30% of deep wound infections are associated with an anastomotic leak. They can lead not only to high rates of graft loss, but also to substantial mortality. New modifications of established techniques are being developed, such as gastric or duodenal exocrine drainage. Duodenoduodenostomy is an interesting option, in which the pancreas is placed behind the right colon and is oriented cephalad. The main concern of this technique is the challenge of repairing the native duodenum when allograft pancreatectomy is necessary. Identification and prevention of technical failure remains the main objective for pancreas transplantation surgeons. In conclusion, despite numerous techniques to minimize exocrine pancreatic drainage complications e.g., leakage and infection, no universal technique has been standardized. A prospective study/registry analysis may resolve this.

Purpose To assess the effectiveness, safety, and overall survival (OS) of thermal ablation as upfront treatment of intrahepatic colangiocarcinoma (ICC) in patients with cirrhosis. Materials and Methods This was a retrospective analysis of all biopsy-confirmed ICC in cirrhotic patients treated in the authors’ unit from 2001 to 2017. Baseline characteristics, ablation procedures, and complications were recorded, and time to recurrence (TTR) and OS were calculated. Twenty-seven patients were identified. Seventy percent had Child-Pugh A disease, and most had clinically significant portal hypertension. Median tumor size was 21 mm. Twenty-one cases were uninodular, and 10 were single ≤ 2 cm. Results Complete radiologic necrosis was achieved in 25 cases (92.6%). Median OS was 30.6 months (95% confidence interval [CI], 22.6–46.5), and recurrence was detected in 21 cases (77.8%) with a TTR of 10.1 months (95% CI, 7.7–20.9). In those patients with single ≤ 2-cm ICC, the OS was 94.5 months (95% CI, 11.7–not reached). Differences in OS were statistically significant between patients with single ICC ≤ 2 cm and patients with single ICC > 2 cm (P = .04) and between patients with single ICC > 2 cm and patients with multinodular ICC (P = .02). Only 1 patient had a treatment-related complication. Conclusions Thermal ablation is a safe and effective treatment for ICC in patients with cirrhosis who are not candidates for surgery. The OS is similar to that reported in surgical series, but the initial treatment success is hampered by a high rate of tumor recurrence. Encouraging long-term survival after thermal ablation is achieved in patients with single ≤ 2-cm ICC.

Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000–2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions., This work was supported by grant from Ministerio de Ciencia, Innovación y Universidades, reference PID2019-104130RB-I00 awarded to EF-P.

Pancreas graft status in simultaneous pancreas-kidney transplant (SPKTx) is currently assessed by nonspecific biochemical markers, typically amylase or lipase. Identifying a noninvasive biomarker with good sensitivity in detecting early pancreas graft rejection could improve SPKTx management.Here, we developed a pilot study to explore donor-derived cell-free DNA (dd-cfDNA) performance in predicting biopsy-proven acute rejection (P-BPAR) of the pancreas graft in a cohort of 36 SPKTx recipients with biopsy-matched plasma samples. dd-cfDNA was measured using the Prospera test (Natera, Inc.) and reported both as a fraction of the total cfDNA (fraction; %) and as concentration in the recipient's plasma (quantity; copies/mL).In the absence of P-BPAR, dd-cfDNA was significantly higher in samples collected within the first 45 d after SPKTx compared with those measured afterward (median, 1.00% versus 0.30%; median, 128.2 versus 35.3 cp/mL, respectively with both; P = 0.001). In samples obtained beyond day 45, P-BPAR samples presented a significantly higher dd-cfDNA fraction (0.83 versus 0.30%; P = 0.006) and quantity (81.3 versus 35.3 cp/mL; P = 0.001) than stable samples. Incorporating dd-cfDNA quantity along with dd-cfDNA fraction outperformed dd-cfDNA fraction alone to detect active rejection. Notably, when using a quantity cutoff of 70 cp/mL, dd-cfDNA detected P-BPAR with a sensitivity of 85.7% and a specificity of 93.7%, which was more accurate than current biomarkers (area under curve of 0.89 for dd-cfDNA (cp/ml) compared with 0.74 of lipase and 0.46 for amylase).dd-cfDNA measurement through a simple noninvasive blood test could be incorporated into clinical practice to help inform graft management in SPKTx patients.

Treatment for hepatocellular carcinoma (HCC) has experienced major advancements since the last update of the official Barcelona Clinic Liver Cancer (BCLC) prognosis and treatment strategy published in 2018. Advancements in the field have emerged in all areas, but in this manuscript, we present those that have primed a change in the strategy and comment why some encouraging data in select interventions are still considered immature and in need of further research to gain their incorporation into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that is needed to take clinical decisions in individual patients so that the recommendation takes into account all the needed parameters to allow a personalised approach.

Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15–35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.

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.

Objective To analyse trends in the use of diagnostic test in breast cancer screening programs in Spain. Materials and methods Retrospective study of 542,695 women who had undergone at least one screening mammogram in any of the screening centres of three administrative regions in Spain, between 1996 and 2011. Process measures were: overall recall rate, overall invasive test rate, and rates of each type of invasive test (fine-needle aspiration biopsy, core-needle biopsy and surgical biopsy). As results measures were included detection of benign lesions rate, ductal in situ cancer rate and invasive cancer rate. Adjusted by age rates were estimated year by year for each measure and, also, the annual percent of change and its corresponding joint points. Results Core-needle biopsy rates decreased between 1996 and 1999 and changed trends in 1999–2011 with an increase of 4.9% per year. Overall recall rate declined by 4.6% from 1999 to 2004, invasive test rate declined between 1996 and 2004 by 24.3%. Fine-needle aspiration biopsy rate changes were: a 22.4% declined per year (1996–1998), and 13.5% declined per year (1998–2005). Benign lesions rate decreased from 1996 to 2011, 21.4% per year (1996–2001) and 6.0% (2001–2011). Ductal carcinoma in situ and invasive cancer had no-statistically significant changes. Conclusion The introduction of core-needle biopsy was slow and not concurrent with the reduction in the use of other diagnostic tests, but also represented a reduction in the rate of overall diagnostic tests and in the detection rate of benigns lesions without affecting the cancer detection rates.

The strict selection of pancreas for transplant has forced the development of different documents to select the suitable organ in order to minimize the risks and complications of the transplant. In 2008, Eurotransplant published the Preprocurement Pancreas Allocation Suitability Score (P-PASS) for pretransplant selection. In 2001 the Hospital Clinic of Barcelona developed a Clinical Consensus Document (CCD). Objectives We aimed to analyze the predictive decision of the pancreas acceptance to offers received in the hospital, according to the CCD criteria and compare it with the recommended value of suitability for accepting the pancreas according to the P-PASS value. Material and Methods We performed a retrospective comparative study between the criteria of selection of the CCD for pancreas from 2016–2017 in comparison with the values obtained if the P-PASS had been used: ≤ 17, acceptance criteria and P-PASS; > 17, risk criteria. We defined the organ reported as rejected or accepted. The accepted organ could be procured and transplanted or discarded. Results With the CCD criteria, 7 more organs were transplanted than if we only applied the potential P-PASS criteria. In contrast, P-PASS would have ruled out an additional 9% of pancreases in relation to CCD criteria. Conclusions According our experience, it is difficult to find an adequate prediction model to select pancreas for transplantation. The application of the DCC criteria increases the number of organs valid for transplantation. At present, new criteria should be re-evaluated within multicenter studies.

Resumen Introduccion Actualmente la variabilidad en la practica quirurgica constituye un problema a resolver. El objetivo de nuestro estudio es describir la variabilidad en la realizacion del tratamiento quirurgico del cancer de mama y analizar los factores asociados a la misma. Metodos La poblacion de estudio comprende 1.057 mujeres diagnosticadas de cancer de mama y tratadas quirurgicamente procedentes de la cohorte retrospectiva CaMISS. Resultados La edad media en el momento del diagnostico fue de 59,3 ± 5 anos. Se diagnosticaron 732 pacientes mediante mamografias de cribado y 325 pacientes como canceres de intervalo. La realizacion de mastectomia fue mas frecuente en los tumores detectados entre intervalos (OR = 2,5; [IC 95%: 1,8-3,4]), aunque este efecto desaparece al ajustar por el resto de variables. El factor mas determinante asociado a la realizacion de una mastectomia fue el TNM: los tumores con estadio iii - iv presentaron una OR de 7,4 (IC 95%: 3,9-13,8), aumentando en la OR ajustada hasta 21,7 (IC 95%: 11,4-41,8). Histologicamente el carcinoma lobulillar infiltrante mantiene la significacion en la OR ajustada (ORa = 2,5; [IC 95%: 1,4-4,7]). Segun el programa de cribado existen diferencias significativas en el tratamiento quirurgico. El programa 3 presenta una ORa de cirugia tipo mastectomia de 4 [IC 95%: 1,8-8,9]. Este programa coincide con el de mayor porcentaje de reconstruccion (58,3%). Conclusiones Este estudio muestra como a pesar de tener en cuenta las caracteristicas de las pacientes y del tumor, existe una elevada variabilidad en el tipo de cirugia en funcion del lugar de diagnostico.

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation., We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.

Evaluate the weight trajectories after pancreas transplantation (PT) and their relationships with pancreas graft outcomes in type 1 diabetes (T1D).Retrospective cohort study. T1D individuals who underwent PT were recruited (T1D-PT; n = 194) and divided into three groups according to transplantation date: 1999-2004 (n = 57), 2005-2009 (n = 79), 2010-2015 (n = 58). For weight comparisons, a random sample of T1D without renal impairment was also recruited during 2015 (n = 61; T1D-control).The median follow-up for the T1D-PT group was 11.1 years. Despite significant weight loss at 6 months (65.7 ± 12.4 vs. 64.1 ± 11.4 Kg; p 0.001), a stepped increase was seen thereafter (60 months: 68.0 ± 14.0 Kg; p 0.001). Participants from the 2010-2015 period showed higher weight gain (p 0.001), outweighing that observed in the T1D-control (60 months: +4.69 ± 8.49 vs. -0.97 ± 4.59 Kg; p = 0.003). Weight gain between 6 and 36 months was directly associated with fasting glucose and HbA1c at 36 months, and with HbA1c at 60 months (p 0.05). However, in Cox-regression models adjusted for age, sex, and several recipient and PT-related variables, the third tertile of weight gain between 6 and 36 months showed a non-significant increase in the graft failure/dysfunction (HR 2.33 [0.75-7.27]).Weight gain post-PT was associated with glucose-related biochemical markers of graft dysfunction, which needs confirmation in further studies.

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one that includes kidney function as a risk factor, which is a well-described independent risk factor for cardiovascular disease.We explore how simultaneous pancreas-kidney transplantation (SPKT) modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016.Two hundred sixty-eight SPKT recipients with a mean age of 40 y old and a median follow-up of 10 y were included. Before transplantation, the expected incidence of cardiovascular events (CVEs) at 5 and 10 y according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th-mo glomerular filtration rate (at 5 and 10 y predicted CVE incidence was 10.5% and 19.4%, respectively). Early pancreas graft failure (hazard ratio [HR] 3.00, 95% confidence interval [CI], 1.14-7.88; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside kidney graft failure (HR 2.90, 95% CI, 1.53-5.48; P = 0.001), and diabetes duration (HR 1.04, 95% CI, 1.00-1.09, P = 0.04).SPKT decreases in more than two-thirds of the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.

New chemotherapy schemes have allowed for a better radiological response of unresectable colorectal liver metastases, leading to an interesting scenario known as a complete radiological response. The aim of this study was to review the current management of missing liver metastases (MLM) from the liver surgeon’s point of view. A systematic search was conducted on all publications of PubMed and Embase between 2003 and 2018. Meta-analysis was performed on MLM resected/unresected. Residual tumor or regrowth and relapse-free survival were used as evaluation indices. After literature search, 18 original articles were included for analysis. The predictive factors for MLM are type and duration of chemotherapy and size and number of lesions. Magnetic resonance is the most sensitive preoperative technique. Regarding clinical management, liver surgery is deemed the fundamental pillar in the therapeutic strategy of these patients. Meta-analysis due to data heterogeneity was inconclusive. Depending on the clinical context, MLM monitoring appears to be a valid therapeutic alternative. Nevertheless, prospective randomized clinical studies are needed.

BackgroundComplications and readmissions derived from surgical treatment of breast cancer have been scarcely evaluated. The studies that compare mastectomy with conservative, usually focus only in recurrence and/or mortality and sometimes the results are discordant in some aspects. The aim of this study was to analyze complications and readmissions, recurrence and mortality, according to the surgical treatment received in the mammary gland.Methods This multicenter study included 1086 women diagnosed with breast cancer from the CaMISS cohort study of women aged between 50 and 69 years participating in 4 breast cancer screening programs in Spain between 2000 and 2009 with a follow up until 2014. Multivariate models were used to estimate the adjusted odds ratio of breast surgery (mastectomy vs conservative treatment) for complications and readmissions and hazard ratios for recurrences and mortality.Results Primary breast surgical treatment consisted of conservative treatment in 821 women (80.1%) and mastectomy in 204 (19.9%). Mastectomy was associated with readmissions, recurrences and mortality but this association was not statistically significant on multivariate adjusted analysis (ORa=1.51 [95%CI 0.89-2.57], HRa=1.37 [95%CI 0.85-2.19] and HRa=1.52 [95%CI 0.95-2.43] respectively). In our sample, the variables with greatest impact on complications, recurrences and mortality were stages III and IV (ORa=4.4 [95%CI 1.22-16.16], HRa=7.96 [95%CI 3.32-19.06] and HRa=3.92 [95%CI 1.77-8.67]). Conclusion Complications, readmissions, recurrence and mortality were similar in both surgical techniques. These results support that surgical treatment for breast cancer can be adapted to professional and health system circumstances, and to the surgical needs and desires of each patient.

Introduction: The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. Methods: This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery. Results: Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. Conclusions: Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.

Background & Aims Defining optimum management of patients progressing beyond Milan criteria on the waiting list is a controversial topic. Our aim was to determine whether the policy of allowing a limited progression beyond enlistment criteria permits acceptable post-transplant outcomes in terms of survival and recurrence. Methods Patients with hepatocellular carcinoma included on the waiting list for orthotopic liver transplantation (OLT) between January 1989 and December 2016 were analysed. Tumour features were assessed at inclusion on the waiting list, before OLT and at explant pathology. Patients were retained on the waiting list despite exceeding enlistment criteria if not presenting with macrovascular invasion, extrahepatic spread or cancer-related symptoms. Results A total of 495 patients constituted the target population. Comparison between the Milan-in (n = 434) and Milan-out (n = 61) groups showed statistically significant differences in: largest tumour size; BCLC stage; patients treated before OLT; alpha-fetoprotein, and time on the waiting list. Milan-out patients showed a significantly higher number of poorly differentiated nodules, satellitosis and microscopic vascular invasion. The 1-, 3-, 5- and 10-year survival rate was 89.6%, 82.5%, 75%, and 55.5%, vs. 83.6%, 70.5%, 65.5%, and 53.9% for Milan-in/Milan-out patients, respectively. Recurrence rates at 1, 3, 5 and 10 years were 1.2%, 3.3%, 5.5%, and 10.8% vs. 7.1% 14.5%, 23%, and 23% for Milan-in and Milan-out patients, respectively (p Conclusion This study shows that although limited tumour progression without reaching major adverse predictors (vascular invasion, extrahepatic spread, cancer symptoms) has an expected impact on recurrence rate, overall survival remains above the minimum proposed benchmark of 65% at 5 years. The clinically relevant increase in tumour recurrence must be considered when analysing the benefit of this approach in the face of limited organ supply. Lay summary When considering orthotopic liver transplantation for patients with hepatocellular carcinoma, optimum results are achieved when transplanting patients within the Milan criteria. However, the most appropriate strategy for patients who progress beyond these criteria while on the waiting list is still unclear. Herein, we show that transplantation is associated with acceptable overall survival in select patients who progress beyond the Milan criteria, although recurrence rates were notably higher. Therefore, the assessment of transplantation viability in these patients must consider the availability of organs and the impact on other patient categories.

Enteric complications remain a major cause of morbidity in the post-transplant period of pancreas transplantation despite improvements surgical technique. The aim of this single-center study was to analyze retrospectively the early intestinal complications and their potential relation with vascular events. From 2000 to 2016, 337 pancreas transplants were performed with systemic venous drainage. For exocrine secretion, intestinal drainage was done with hand-sewn anastomosis duodenojejunostomy. Twenty-three patients (6.8%) had early intestinal complications. Median age was 39 years (male: 65.2%). Median cold ischemia time was 11 h [IQR: 9-12.4]. Intestinal complications were intestinal obstruction (n = 7); paralytic ileus (n = 5); intestinal fistula without anastomotic dehiscence (n = 3); ischemic graft duodenum (n = 3); dehiscence of duodenojejunostomy (n = 4); and anastomotic dehiscence in jejunum after pancreas transplantectomy (n = 1). Eighteen cases required relaparotomy: adhesiolysis (n = 6); repeated laparotomy without findings (n = 1); transplantectomy (n = 6); primary leak closure (n = 3); re-positioning of the graft (n = 1); and intestinal resection (n = 1). Of the intestinal complications, 4 were associated with vascular thrombosis, resulting in two pancreatic graft losses. Enteric drainage with duodenum-jejunum anastomosis is safe and feasible, with a low rate of intra-abdominal complications. Vascular thrombosis associated with intestinal complications presents a risk factor for the viability of pancreatic grafts, so prevention and early detection is vital.

The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients.This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery.Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas.Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.