Liver Histology Predicts Liver Regeneration and Outcome in ALPPS: Novel Findings From A Multicenter Study.

BACKGROUND AND AIMS: Alterations in liver histology influence the liver's capacity to regenerate, but the relevance of each of the different changes in rapid liver growth induction is unknown. This study aimed to analyze the influence of the degree of histological alterations during the first and second stages on the ability of the liver to regenerate. METHODS: This cohort study included data obtained from the International ALPPS Registry between November 2011 and October 2020. Only patients with colorectal liver metastases were included in the study. We developed a histological risk score based on histological changes (stages 1 and 2) and a tumor pathology score based on the histological factors associated with poor tumor prognosis. RESULTS: In total, 395 patients were included. The time to reach stage 2 was shorter in patients with a low histological risk stage 1 (13 vs 17 days, P ˂0.01), low histological risk stage 2 (13 vs 15 days, P <0.01), and low pathological tumor risk (13 vs 15 days, P <0.01). Regarding interval stage, there was a higher inverse correlation in high histological risk stage 1 group compared to low histological risk 1 group in relation with future liver remnant body weight ( r =-0.1 and r =-0.08, respectively), and future liver remnant ( r =-0.15 and r =-0.06, respectively). CONCLUSIONS: ALPPS is associated with increased histological alterations in the liver parenchyma. It seems that the more histological alterations present and the higher the number of poor prognostic factors in the tumor histology, the longer the time to reach the second stage.

How to Handle Arterial Conduits in Liver Transplantation? Evidence From the First Multicenter Risk Analysis.

OBJECTIVE: The aims of the present study were to identify independent risk factors for conduit occlusion, compare outcomes of different AC placement sites, and investigate whether postoperative platelet antiaggregation is protective. BACKGROUND: Arterial conduits (AC) in liver transplantation (LT) offer an effective rescue option when regular arterial graft revascularization is not feasible. However, the role of the conduit placement site and postoperative antiaggregation is insufficiently answered in the literature. STUDY DESIGN: This is an international, multicenter cohort study of adult deceased donor LT requiring AC. The study included 14 LT centers and covered the period from January 2007 to December 2016. Primary endpoint was arterial occlusion/patency. Secondary endpoints included intra- and perioperative outcomes and graft and patient survival. RESULTS: The cohort was composed of 565 LT. Infrarenal aortic placement was performed in 77% of ACs whereas supraceliac placement in 20%. Early occlusion (≤30 days) occurred in 8% of cases. Primary patency was equivalent for supraceliac, infrarenal, and iliac conduits. Multivariate analysis identified donor age >40 years, coronary artery bypass, and no aspirin after LT as independent risk factors for early occlusion. Postoperative antiaggregation regimen differed among centers and was given in 49% of cases. Graft survival was significantly superior for patients receiving aggregation inhibitors after LT. CONCLUSION: When AC is required for rescue graft revascularization, the conduit placement site seems to be negligible and should follow the surgeon's preference. In this high-risk group, the study supports the concept of postoperative antiaggregation in LT requiring AC.

Repeated hepatectomy after ALPPS for recurrence of colorectal liver metastasis: the edge of limits?

BACKGROUND: Repeated liver resections for the recurrence of colorectal liver metastasis (CRLM) are described as safe and have similar oncological outcomes compared to first hepatectomy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is performed in patients with conventionally non-resectable CRLM. Repeated resections after ALPPS has not yet been described. METHODS: Patients that underwent repeated liver resection in recurrence of CRLM after ALPPS were included in this study. The primary endpoint was morbidity and secondary endpoints were mortality, resection margin and survival. RESULTS: Thirty patients were included in this study. During ALPPS, most of the patients had classical split (60%, n = 18) and clearance of the FLR (77%, n = 23). Hepatic recurrence was treated with non-anatomical resection (57%, n = 17), resection combined with local ablation (13%, n = 4), open ablation (13%, n = 4), segmentectomy (10%, n = 3) or subtotal segmentectomy (7%, n = 2). Six patients (20%) developed complications (10% minor complications). No post-hepatectomy liver failure or perioperative mortality was observed. One-year patient survival was 87%. Five patients received a third hepatectomy. CONCLUSION: Repeated resections after ALPPS for CRLM in selected patients are safe and feasible with low morbidity and no mortality. Survival seems to be comparable with repeated resections after conventional hepatectomy.

MAIT cells launch a rapid, robust and distinct hyperinflammatory response to bacterial superantigens and quickly acquire an anergic phenotype that impedes their cognate antimicrobial function: Defining a novel mechanism of superantigen-induced immunopathology and immunosuppression.

Superantigens (SAgs) are potent exotoxins secreted by Staphylococcus aureus and Streptococcus pyogenes. They target a large fraction of T cell pools to set in motion a "cytokine storm" with severe and sometimes life-threatening consequences typically encountered in toxic shock syndrome (TSS). Given the rapidity with which TSS develops, designing timely and truly targeted therapies for this syndrome requires identification of key mediators of the cytokine storm's initial wave. Equally important, early host responses to SAgs can be accompanied or followed by a state of immunosuppression, which in turn jeopardizes the host's ability to combat and clear infections. Unlike in mouse models, the mechanisms underlying SAg-associated immunosuppression in humans are ill-defined. In this work, we have identified a population of innate-like T cells, called mucosa-associated invariant T (MAIT) cells, as the most powerful source of pro-inflammatory cytokines after exposure to SAgs. We have utilized primary human peripheral blood and hepatic mononuclear cells, mouse MAIT hybridoma lines, HLA-DR4-transgenic mice, MAIThighHLA-DR4+ bone marrow chimeras, and humanized NOD-scid IL-2Rγnull mice to demonstrate for the first time that: i) mouse and human MAIT cells are hyperresponsive to SAgs, typified by staphylococcal enterotoxin B (SEB); ii) the human MAIT cell response to SEB is rapid and far greater in magnitude than that launched by unfractionated conventional T, invariant natural killer T (iNKT) or γδ T cells, and is characterized by production of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-2, but not IL-17A; iii) high-affinity MHC class II interaction with SAgs, but not MHC-related protein 1 (MR1) participation, is required for MAIT cell activation; iv) MAIT cell responses to SEB can occur in a T cell receptor (TCR) Vß-specific manner but are largely contributed by IL-12 and IL-18; v) as MAIT cells are primed by SAgs, they also begin to develop a molecular signature consistent with exhaustion and failure to participate in antimicrobial defense. Accordingly, they upregulate lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin-3 (TIM-3), and/or programmed cell death-1 (PD-1), and acquire an anergic phenotype that interferes with their cognate function against Klebsiella pneumoniae and Escherichia coli; vi) MAIT cell hyperactivation and anergy co-utilize a signaling pathway that is governed by p38 and MEK1/2. Collectively, our findings demonstrate a pathogenic, rather than protective, role for MAIT cells during infection. Furthermore, we propose a novel mechanism of SAg-associated immunosuppression in humans. MAIT cells may therefore provide an attractive therapeutic target for the management of both early and late phases of severe SAg-mediated illnesses.

Defining Benchmark Outcomes for ALPPS.

OBJECTIVE: The aim of this study was to use the concept of benchmarking to establish robust and standardized outcome references after the procedure ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy). BACKGROUND AND AIMS: The recently developed ALPPS procedure, aiming at removing primarily unresectable liver tumors, has been criticized for safety issues with high variations in the reported morbidity/mortality rates depending on patient, disease, technical characteristics, and center experience. No reference values for relevant outcome parameters are available. METHODS: Among 1036 patients registered in the international ALPPS registry, 120 (12%) were benchmark cases fulfilling 4 criteria: patients ≤67 years of age, with colorectal metastases, without simultaneous abdominal procedures, and centers having performed ≥30 cases. Benchmark values, defined as the 75th percentile of the median outcome parameters of the centers, were established for 10 clinically relevant domains. RESULTS: The benchmark values were completion of stage 2: ≥96%, postoperative liver failure (ISGLS-criteria) after stage 2: ≤5%, ICU stay after ALPPS stages 1 and 2: ≤1 and ≤2 days, respectively, interstage interval: ≤16 days, hospital stay after ALPPS stage 2: ≤10 days, rates of overall morbidity in combining both stage 1 and 2: ≤65% and for major complications (grade ≥3a): ≤38%, 90-day comprehensive complication index was ≤22, the 30-, 90-day, and 6-month mortality was ≤4%, ≤5%, and 6%, respectively, the overall 1-year, recurrence-free, liver-tumor-free, and extrahepatic disease-free survival was ≥86%, ≥50%, ≥57%, and ≥65%, respectively. CONCLUSIONS: This benchmark analysis sets key reference values for ALPPS, indicating similar outcome as other types of major hepatectomies. Benchmark cutoffs offer valid tools not only for comparisons with other procedures, but also to assess higher risk groups of patients or different indications than colorectal metastases.

Can we reduce ischemic cholangiopathy rates in donation after cardiac death liver transplantation after 10 years of practice? Canadian single-centre experience

Background: Outcomes in liver transplantation with organs obtained via donation after cardiocirculatory death (DCD) have been suboptimal compared to donation after brain death, attributed mainly to the high incidence of ischemic cholangiopathy (IC). We evaluated the effect of a 10-year learning curve on IC rates among DCD liver graft recipients at a single centre. Methods: We analyzed all DCD liver transplantation procedures from July 2006 to July 2016. Patients were grouped into early (July 2006 to June 2011) and late (July 2011 to July 2016) eras. Those with less than 6 months of follow-up were excluded. Primary outcomes were IC incidence and IC-free survival rate. Results: Among the 73 DCD liver transplantation procedures performed, 70 recipients fulfilled the selection criteria, 32 in the early era and 38 in the late era. Biliary complications were diagnosed in 19 recipients (27%). Ischemic cholangiopathy was observed in 8 patients (25%) in the early era and 1 patient (3%) in the late era (p = 0.005). The IC-free survival rate was higher in the late era than the early era (98% v. 79%, p = 0.01). The warm ischemia time (27 v. 24 min, p = 0.049) and functional warm ischemia time (21 v. 17 min, p = 0.002) were significantly lower in the late era than the early era. Conclusion: We found a significant reduction in IC rates and improvement in ICfree survival among DCD liver transplantation recipients after a learning curve period that was marked by more judicious donor selection with shorter procurement times.

Contexte: L'issue des greffes de foie suite à un don d'organe après décès cardiocirculatoire (DDC) a été sous-optimale comparativement aux dons suivant la mort cérébrale. Cela serait surtout attribuable à une forte incidence de cholangiopathie ischémique (CI). Nous avons évalué l'effet d'une courbe d'apprentissage échelonnée sur 10 ans sur les taux de CI chez des receveurs de greffe de foie après DDC dans un seul centre. Méthodes: Nous avons analysé toutes les greffes de foie consécutives à des DDC entre juillet 2006 et juillet 2016. Les patients ont été regroupés en 2 époques, la première, de juillet 2006 à juin 2011, et la seconde, de juillet 2011 à juillet 2016. Ceux pour lesquels on disposait de moins de 6 mois de suivi ont été exclus. Les paramètres principaux étaient l'incidence de CI et le taux de survie sans CI. Résultats: Parmi les 73 greffes de foie par suite de DDC, 70 receveurs répondaient aux critères de sélection, 32 pour la première époque et 38 pour la seconde époque. Des complications biliaires ont été diagnostiquées chez 19 receveurs (27 %). La cholangiopathie ischémique a été observée chez 8 patients (25 %) de la première époque et 1 patient (3 %) de la seconde (p = 0,005). Le taux de survie sans CI a été plus élevé pendant la seconde époque que pendant la première (98 % c. 79 %, p = 0,01). Le temps d'ischémie chaude (27 minutes c. 24, p = 0,049) et le temps d'ischémie chaude fonctionnelle (21 minutes c. 17, p = 0,002) ont été significativement plus courts durant la seconde époque que durant la première. Conclusion: Nous avons observé une réduction significative des taux de CI et une amélioration de la survie sans CI chez les receveurs de greffes de foie par DDC après une courbe d'apprentissage qui a été marquée par une sélection plus judicieuse des donneurs et des délais d'obtention plus courts.

Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment.

Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection. We found that MAIT cells, defined as CD3ε+Vα7.2+CD161++ or CD3ε+MR1 tetramer+ cells, were present within both healthy and tumor-afflicted hepatic tissues. Paired and grouped analyses of samples revealed the physical proximity of MAIT cells to metastatic lesions to drastically influence their functional competence. Accordingly, unlike those residing in the healthy liver compartment, tumor-infiltrating MAIT cells failed to produce IFN-γ in response to a panel of TCR and cytokine receptor ligands, and tumor-margin MAIT cells were only partially active. Furthermore, chemotherapy did not account for intratumoral MAIT cell insufficiencies. Our findings demonstrate for the first time that CRLM-penetrating MAIT cells exhibit wide-ranging functional impairments, which are dictated by their physical location but not by preoperative chemotherapy. Therefore, we propose that MAIT cells may provide an attractive therapeutic target in CRC and that their ligands may be combined with chemotherapeutic agents to treat CRLM.

Expanding the limits of resectability: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) using monosegment 6, facilitated by an inferior right hepatic vein.

We describe our technique using the combination of a recent surgical technique (ALPPS) and an anomalous vascular anatomy to push the current limits of liver resectability. The approach allowed the resection of the three hepatic veins and preserved a peripheral segment 6 as the only future liver remnant, having an inferior hepatic vein as its outflow.

Patient Survival After Simultaneous ALPPS and Colorectal Resection.

BACKGROUND: Liver resection combined with colorectal surgery (CRS) is the only curative option in many patients presenting with synchronous colorectal cancer and liver metastases (CRLM). Simultaneous resection has been shown to offer benefits in patients with low hepatic tumor load; however, in the setting of in situ colorectal tumor with extensive CRLM and a small predicted future liver remnant (FLR), the use of simultaneous ALPPS and CRS is controversial, lacking outcome data. METHODS: Thirty-one cases of simultaneous ALPPS and CRS prospectively entered into the International ALPPS Registry were examined. Univariate analysis was used to identify factors associated with 90-day mortality after stage-2. RESULTS: Thirty patients (97%) completed both stages. CRS was performed during stage-1 in 22 patients (73%). Seven patients (23%) had severe complications (Clavien-Dindo ≥ IIIb) following stage-2 ALPPS. The 90-day mortality rate was 15%. Patients who had a severe complication after stage-1 were significantly more likely to have 90-day mortality following stage-2 (p = 0.002). MELD score > 10 on postoperative day-5 after stage-1 was also significantly associated with 90-day mortality (p = 0.011). Disease-free survival and overall survival were 36% and 76% at 1 year, respectively. CONCLUSIONS: In light of the high mortality and poor long-term survival identified in this series, the adoption of ALPPS with CRS cannot be recommended without further data. Patients who suffer severe complications or have an elevated MELD score after stage-1 are at higher risk of mortality following stage-2.

Optimizing associated liver partition and portal vein ligation for staged hepatectomy outcomes: Surgical experience or appropriate patient selection?

BACKGROUND: Early reports of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) outcomes have been suboptimal. The literature has confirmed that learning curves influence surgical outcomes. We have 54 months of continuous experience performing ALPPS with strict selection criteria. This study aimed to evaluate the impact of the learning curve on ALPPS outcomes. METHODS: We retrospectively compared patients who underwent ALPPS between April 2012 and March 2016. Patients were grouped into 2 24-month (early and late) periods. All candidates had a high tumour load requiring staged hepatectomy after chemotherapy response, a predicted future liver remnant (FLR) less than 30% and good performance status. RESULTS: Thirty-three patients underwent ALPPS during the study period: 16 in the early group (median age 65 yr, mean body mass index [BMI] 27) and 17 in the late group (median age 60 yr, mean BMI 25). Bilobar disease was comparable in both groups (94% v. 88%, p > 0.99). Duration of surgery was not statistically different. Intraoperative blood loss and need for transfusion were significantly lower in the late group (200 ± 109 mL v. 100 ± 43 mL, p < 0.05). The late group had a higher proportion of monosegment ALPPS (4:1). There were no deaths within 90 days in either cohort. Rates of postoperative complications were not statistically significant between groups. The R0 resection rate was similar. The entire 1-year disease-free and overall survival were 52% and 84%, respectively. CONCLUSION: Excellent results can be obtained in innovative complex surgery with careful patient selection and good technical skills. Additionally, the learning curve brought confidence to perform more complex procedures while maintaining good outcomes.

CONTEXTE: Les premiers résultats sur l'association de la partition hépatique et de la ligature portale pour l'hépatectomie en 2 temps (ALPPS) sont sous-optimaux. La littérature a confirmé que les courbes d'apprentissage influencent les résultats des interventions chirurgicales. Notre étude reposait sur 54 mois consécutifs d'utilisation de la technique ALPPS selon des critères de sélection rigoureux. Elle visait à évaluer l'effet de la courbe d'apprentissage sur les résultats liés à l'ALPPS. MÉTHODES: Nous avons procédé à une comparaison rétrospective des patients traités par l'ALPPS entre avril 2012 et mars 2016. Nous avons divisé les patients en 2 groupes de 24 mois (précoce et tardif). Tous les candidats avaient une charge tumorale élevée nécessitant une hépatectomie en 2 temps après une réponse à la chimiothérapie, un volume estimé de futur foie résiduel (FFR) inférieur à 30 % et un indice fonctionnel favorable. RÉSULTATS: Trente-trois patients ont été traités par l'ALPPS pendant la période de l'étude : 16 dans le groupe précoce (âge médian 65 ans, indice de masse corporelle [IMC] moyen 27) et 17 dans le groupe tardif (âge médian 60 ans, IMC moyen 25). Le taux de maladie bilobaire était comparable entre les 2 groupes (94 % c. 88 %, p > 0,99). La durée de la chirurgie n'était pas statistiquement différente. Les pertes de sang peropératoires et le besoin de transfusion étaient significativement inférieurs dans le groupe tardif (200 ± 109 mL c. 100 ± 43 mL, p < 0,05). Le groupe tardif avait une proportion plus élevée d'ALPPS mono-segmentaires (4:1). Il n'y a eu aucun décès dans les 90 jours parmi les 2 cohortes. Les taux de complications postopératoires n'étaient pas statistiquement significatifs entre les groupes. Le taux de résection R0 était similaire. Les taux de survie sans récidive après une année complète et de survie globale étaient de 52 % et de 84 %, respectivement. CONCLUSION: L'innovation dans le domaine des chirurgies complexes peut donner d'excellents résultats lorsqu'on sélectionne attentivement les patients et que l'on possède de bonnes habiletés techniques. De plus, la courbe d'apprentissage a eu pour effet d'accroître la confiance dans la capacité de réaliser des interventions complexes tout en produisant de bons résultats.

Renal transplant waiting list mortality in COVID era: is it advisable to halt transplant activity?

INTRODUCTION: Kidney transplantation is the treatment of choice for end-stage renal disease (ESRD). Since March 2020, transplant activity in Mexico has been affected due to the COVID-19 pandemic. OBJECTIVE: The aim of the study was to determine the impact on mortality of patients on the waiting list (WL) for cadaveric donor kidney transplantation in a referral hospital in Yucatán, due to suspension of activities due to the pandemic. MATERIAL AND METHODS: Patients over 18 years of age on the waiting list for kidney transplantation at this hospital. In the event of a patient's death, the cause was investigated, especially if it was associated with COVID-19. A two-tailed p ≤ 0.05 was considered significant in all analyzes. RESULTS: The odds ratio (OR) of death from COVID-19 in a patient with ESRD in the WL in 2020 was OR = 5.04 (95% CI: 1.65-7.14, p = 0.023). The OR of dying with ESRD in the WL with a delay in the follow-up visits was OR = 6.59 (95% CI: 2.7-16.28, p = 0.008). CONCLUSION: The probability of death of a patient with ESRD with delayed follow-up visits and transplant retention is statistically higher than the probability of death from COVID-19.

INTRODUCCIÓN: El trasplante renal es el tratamiento de elección de la enfermedad renal en etapa terminal (ERT). Desde marzo de 2020, la actividad de trasplantes en México se ha visto afectada debido a la pandemia de COVID-19. OBJETIVO: Determinar el impacto en la mortalidad de pacientes en lista de espera (LE) para trasplante renal de donante cadavérico en un hospital de referencia en Yucatán, por suspensión de actividades debido a la pandemia. MATERIAL Y MÉTODOS: Pacientes > 18 años en LE para trasplante renal en este hospital. En caso de muerte de un paciente, se investigó la causa, especialmente si estaba asociada a COVID-19. Un valor de p de dos colas ≤ 0.05 se consideró significativo en todos los análisis. RESULTADOS: La razón de probabilidad de muerte por COVID-19 en un paciente con ERT en la LE en 2020 fue OR = 5.04 (IC 95%: 1.65-7.14, p = 0.023). La razón de probabilidad de morir con ERT en la LE con retraso en las consultas de seguimiento fue de OR = 6.59 (IC 95%: 2.7-16.28, p = 0.008). CONCLUSIÓN: La probabilidad de muerte de un paciente con ERT en la LE con retraso en las consultas de seguimiento y retención del trasplante es estadísticamente más alta que la probabilidad de muerte por COVID-19.

Development and internal validation of the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score: is the patient suitable for Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS)?

Background: Preoperative patient selection in Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is not always reliable with currently available scores, particularly in patients with primary liver tumor. This study aims to (I) to determine whether comorbidities and patients characteristics are a risk factor in ALPPS and (II) to create a score predicting 90-day mortality preoperatively. Methods: Thirteen high-volume centers participated in this retrospective multicentric study. A risk analysis based on patient characteristics, underlying disease and procedure type was performed to identify risk factors and model the Comprehensive ALPPS Preoperative Risk Assessment (CAPRA) score. A nonparametric receiver operating characteristic analysis was performed to estimate the predictive ability of our score against the Charlson Comorbidity Index (CCI), the age-adjusted CCI (aCCI), the ALPPS risk score before Stage 1 (ALPPS-RS1) and Stage 2 (ALPPS-RS2). The model was internally validated applying bootstrapping. Results: A total of 451 patients were included. Mortality was 14.4%. The CAPRA score is calculated based on the following formula: (0.1 × age) - (2 × BSA) + 1 (in the presence of primary liver tumor) + 1 (in the presence of severe cardiovascular disease) + 2 (in the presence of moderate or severe diabetes) + 2 (in the presence of renal disease) + 2 (if classic ALPPS is planned). The predictive ability was 0.837 for the CAPRA score, 0.443 for CCI, 0.519 for aCCI, 0.693 for ALPPS-RS1 and 0.807 for ALPPS-RS2. After 1,000 cycles of bootstrapping the C statistic was 0.793. The accuracy plot revealed a cut-off for optimal prediction of postoperative mortality of 4.70. Conclusions: Comorbidities play an important role in ALPPS and should be carefully considered when planning the procedure. By assessing the patient's preoperative condition in relation to ALPPS, the CAPRA score has a very good ability to predict postoperative mortality.

Bidirectional graft-host hematological traffic in liver transplantation.

The highly complex immuno-hematological system of the recipient has to rebalance itself when the liver is replaced with a graft that has its own system. This gives us an opportunity for observation. Here we consider the graft-to-recipient direction with passenger lymphocyte syndrome (PLS) as well as the recipient-to-graft direction with Factor VIII (FVIII) inhibitors, paroxysmal nocturnal hemoglobinuria (PNH) and graft endothelial replacement with liver transplantation. PLS extends beyond the ABO blood groups to any situation where the donor has been sensitized to a recipient antigen. PLS directed against ABO or minor blood group antigens is usually self limiting whereas Rhesus (Rh) PLS persists with life threatening immune hemolysis. Human platelet antigen (HPA) 1A PLS results in life threatening immune thrombocytopenia. Treatments of severe PLS may include reduction in immunosuppression, anti-B-cell therapy, plasmapheresis and splenectomy. Liver transplantation into recipients with FVIII inhibitors has been difficult. Donors with acquired hemophilia may transmit the capacity to make FVIII inhibitors by PLS and should be avoided. Patients with PNH have been transplanted successfully but a considerable cost in the continued use of high dose eculizumab. We speculate that combined bone marrow and liver transplantation would be a better option for recipients with FVIII inhibitors or PNH. Replacement of liver graft endothelium with recipient cells is common and may explain relative transplant tolerance that is believed to occur with liver transplantation.

Subnormothermic Oxygenated Perfusion Optimally Preserves Donor Kidneys Ex Vivo.

INTRODUCTION: The current methods of preserving donor kidneys in nonoxygenated cold conditions minimally protect the kidney against ischemia-reperfusion injury (IRI), a major source of complications in clinical transplantation. However, preserving kidneys with oxygenated perfusion is not currently feasible due to the lack of an ideal perfusion mechanism that facilitates perfusion with blood at warm temperature. Here, we have designed an innovative renal pump circuit system that can perfuse blood or acellular oxygen carrier under flexible temperatures, pressures, and oxygenation. We have tested this apparatus to study optimal conditions of storage of our porcine model of donation after cardiac death (DCD) kidneys. METHODS: Porcine kidneys were retrieved after 30 minutes of cross-clamping renal pedicles in situ. Cessation of blood mimics postcardiac death in humans and simulates DCD warm ischemic injury. Procured kidneys were flushed and subjected to static cold storage (SCS) for 4 hours. For warm perfusion, kidneys were cannulated for pulsatile oxygenated perfusion with blood:PlasmaLyte for 4 hours at 15 °C, 22 °C, and 37 °C. To mimic posttransplant scenario, all kidneys were reperfused with blood for an additional 4 hours at 37 °C. RESULTS: Compared with all other groups, 22 °C perfusion resulted in significant reduction of acute tubular necrosis (ATN), apoptosis, kidney damage markers, Toll-like receptor signaling, and cytokine production. It was associated with maximal renal blood flow and urine output. Kidneys stored at 15 °C thrombosed within 2 hours under this condition. Martius Scarlet Blue staining confirmed that 22 °C was the optimal temperature to minimize hemorrhage and blood clots. CONCLUSION: Our novel study shows that oxygenated perfusion at near-room-temperature provides optimal donor kidney storage conditions.

Intermediate-term survival and quality of life outcomes in patients with advanced colorectal liver metastases undergoing associating liver partition and portal vein ligation for staged hepatectomy.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is an innovative, 2-staged hepatectomy which has elicited controversy within the international hepatobiliary community. Uptake of ALPPS has been limited due to concerns related to evidence of high morbidity and mortality, and scant oncologic and outcome data on quality of life (Qol). Demonstrating reasonable long-term benefits with a short-term risk is necessary to support more widespread endorsement of ALPPS. Our aim was to describe the intermediate-term survival and patient-reported quality of life outcomes after an ALPPS. METHODS: Prospectively collected data from 2 high-volume ALPPS centers, who were pioneers with the technique, were combined and analyzed for disease-free and overall survival from date of the ALLPS. Only patients treated for colorectal liver metastases with >6 month postoperative follow-up were included. All patients had bilateral colorectal liver metastases with an initially unresectable tumor load, and received preoperative chemotherapy. Information concerning the demographics of the patients, characteristics of the tumor, and treatment were analyzed. The well-validated European Organization for Research and Treatment for Cancer Quality of Life Core Questionnaire version 3.0 questionnaire was used to assess patient quality of life. RESULTS: A total of 58 patients underwent ALPPS for colorectal liver metastases, and 47 patients met our inclusion criteria. There were no perioperative mortalities, and the rate of severe complications was 21%. At 3 years post-ALPPS, the overall survival was 50%, while the disease-free survival was 13%. The commonest site of first recurrence was the liver alone (38%). Patient-reported quality of life after ALPPS was similar to reference values for general population. CONCLUSION: In select patients operated at experienced centers, ALPPS results in low perioperative risk, satisfactory overall survival, and excellent quality of life. Hepatic recurrence and not systemic recurrence is the most common site of relapse after ALPPS.

Management of colorectal cancer with synchronous liver metastases: impact of multidisciplinary case conference review.

BACKGROUND: While no evidence exists to support mandatory multidisciplinary case conference (MCC) review for patients with synchronous colorectal cancer and liver metastases, this unique population may benefit greatly from multidisciplinary discussion. METHODS: We retrospectively identified patients who underwent liver resection with curative intent for colorectal liver metastases (CRLM) at a tertiary center between January 2008 and June 2015. The characteristics of patients discussed at a weekly regional MCC were examined, and the effect of MCC review on treatment approach was assessed. RESULTS: Sixty-six patients underwent elective surgery for synchronous colorectal cancer and liver metastases during the study period. Twenty-nine patients (44%) were presented at a MCC. Presentation was associated with greater likelihood of undergoing simultaneous or liver-first resection (P≤0.0001), with no difference in the extent of liver resection or location of primary tumor between the groups. A greater proportion of patients received chemotherapy and/or radiation following MCC discussion, without statistical significance. CONCLUSIONS: The treatment approach for patients with synchronous colorectal cancer and liver metastases may be significantly altered based on MCC review. Multidisciplinary discussion is advocated in order to facilitate equal access to individualized care.

[Surgical treatment of pancreatic pseudocysts]. / Tratamiento quirúrgico del seudoquiste de páncreas.

BACKGROUND: A pancreatic pseudocyst is the collection of pancreatic secretions surrounded by fibrous tissue caused by pancreatic disease that affects the pancreatic duct. Clinical presentation is variable. Management includes percutaneous, endoscopic or surgical drainage and resection. MATERIAL AND METHODS: Review of a cohort of patients with pancreatic pseudocyst in a third level hospital. An analysis was performed on the demographic data, aetiology, clinical presentation, radiological and laboratory findings, type of surgical procedure, complications, recurrence and mortality. The statistical analysis was performed using Chi squared and Student t tests, with a p<0.05. RESULTS: A total of 139 patients were included, of whom 58% were men and 42% were women, with median age of 44.5 years. Chronic pancreatitis was the most common aetiology, present in 74 patients (53%). The main complaint was abdominal pain in 73% of patients. Median size was 18cm (range 7-29) and the most frequent location was body and tail of the pancreas. Internal surgical drainage was selected in 111 (80%) patients, of whom 96 were cystojejunostomy, 20 (14%) had external surgical drainage, and 8 (6%) resection. Complications were, pancreatic fistula (12%), haemorrhage (4%), infection (4%), and other non-surgical complications (4%). Complication rate was higher if the cause was chronic pancreatitis or if the management was external surgical drainage. Recurrence rate was 6%, and a mortality rate of 1%. CONCLUSION: Surgical management is a viable option for the management of pancreatic pseudocyst with a low complication and recurrence rate.

[Acute pancreatitis associated with hypercalcaemia]. / Pancreatitis aguda asociada con hipercalcemia.

BACKGROUND: Hypercalcaemia due to primary hyperparathyroidism is a rare cause of acute pancreatitis, with a reported prevalence of 1.5 to 8%. There is no clear pathophysiological basis, but elevated parathyroid hormone and high serum calcium levels could be responsible for calcium deposit in the pancreatic ducts and activation of pancreatic enzymes, which may be the main risk factor for developing acute pancreatitis. The aim of this report is to describe four cases. CLINICAL CASE: Four cases are reported of severe pancreatitis associated with hypercalcaemia secondary to primary hyperparathyroidism; three of them with complications (two pseudocysts and one pancreatic necrosis). Cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, studies showed the parathyroid adenoma. Surgical resection was the definitive treatment in all four cases. None of the patients had recurrent acute pancreatitis events during follow-up. CONCLUSIONS: Acute pancreatitis secondary to hypercalcaemia of primary hyperparathyroidism is rare; however, when it occurs it is associated with severe pancreatitis. It is suspected in patients with elevated serum calcium and high parathyroid hormone levels. Imaging techniques such as cervical ultrasound, computed tomography, and scintigraphy using 99mTc-Sestambi, should be performed, to confirm clinical suspicion. Surgical resection is the definitive treatment with excellent results.

[L-lactate as a serum marker of intestinal ischemia in patients with complicated intestinal obstruction]. / L-lactato como marcador sérico de isquemia intestinal en pacientes con oclusión intestinal complicada.

BACKGROUND: The intestinal obstruction secondary to internal hernia is a diagnostic challenge. The absence of specific symptoms and signs during clinical examination often lead to underestimation of the severity and early surgical treatment. The purpose of this article is to review the clinical presentation of two patients with internal hernia, describe the clinical, biochemical and radiological findings, with emphasis on the L-lactate as an early serum marker of intestinal ischemia. CLINICAL CASES: Case 1: female, 44 years history of urolithiasis and 2 cesarean sections. Case 2: female, 86 year old with a history of open cholecystectomy, incisional and bilateral inguinal hernia repair with mesh placement. Both admitted with abdominal pain and intestinal obstruction data. The only significant laboratory finding was elevation of L-lactate. The abdominal films showed air-fluid levels, dilated loops of small intestine and colon. Abdominal contrast tomography showed free abdominal fluid id, internal hernia and torque of mesentery. In both cases, exploratory laparotomy was performed with bowel resection of ischemic segments, with uneventful recovery. CONCLUSIONS: Intestinal ischemia secondary to internal hernia is difficult lt to diagnose. In patients with a high suspicion, signs of intestinal obstruction by plain radiography, the elevation of L-lactate, could help in the early diagnosis of intestinal ischemia and immediate surgical treatment.

[Hepatic artery pseudoaneurysm: report of two cases]. / Pseudoaneurisma de arteria hepática: reporte de dos casos.

BACKGROUND: Hepatic pseudoaneurysm is rare and potentially fatal. It occurs as a consequence of injury to the vascular wall, erosion diathermy through clips, biliary leakage and secondary infection. The main symptom is intra-abdominal bleeding. OBJECTIVE: To communicate the case of two patients with hepatic pseudoaneurysm. CLINICAL CASES: Case 1: We present a 43 year-old male with a history of grade IV liver injury due to blunt abdominal trauma and managed surgically. Case 2: A 67 year-old man with bile duct injury after laparoscopic cholecystectomy. Both patients presented with biliary leakage, abdominal sepsis and late intra-abdominal bleeding. Tomographic studies showed the lesion. Superselective embolization was performed proximal and distal to the lesion with good results. During follow-up, none of them showed signs of recurrent bleeding. CONCLUSIONS: Hepatic artery pseudoaneurysm is rare and usually secondary to bile duct injury associated with vascular injury after cholecystectomy or liver trauma. Arteriography with embolization is the best diagnostic and therapeutic procedure. Surgery is indicated for hemodynamically unstable patients, embolization failure or rebleeding. Early diagnosis reduces morbidity and mortality of this complication.

Antecedentes: el pseudoaneurisma de la arteria hepática es una alteración rara y potencialmente mortal. El daño directo a la pared vascular, la erosión diatérmica a través de los clips, la fuga biliar y la infección secundaria son los factores precipitantes. La principal manifestación es la hemorragia intraabdominal. Objetivo: describir dos casos de pseudoaneurisma de la arteria hepática. Casos clínicos: Caso 1: paciente masculino de 43 años de edad con antecedentes de lesión hepática grado IV por traumatismo cerrado de abdomen tratado quirúrgicamente. Caso 2: paciente masculino de 67 años de edad con lesión en la vía biliar por colecistectomía laparoscópica. Ambos ingresaron con fuga biliar y sepsis abdominal. Durante la evolución posoperatoria sufrieron hemorragia intraabdominal. Por angiotomografía se observó un pseudoaneurisma de la arteria hepática en los dos pacientes. Se les realizó embolización superselectiva proximal y distal a la lesión, con buenos resultados. Durante su seguimiento no hubo nuevos episodios de hemorragia. Conclusiones: el pseudoaneurisma de la arteria hepática es muy raro y, por lo general, secundario a una lesión de la vía biliar, con lesión vascular concomitante por colecistectomía o traumatismo hepático. La angiotomografía es diagnóstica y la arteriografía con embolización es el recurso diagnóstico y terapéutico más recomendado. La intervención quirúrgica está indicada ante inestabilidad hemodinámica, embolización fallida y resangrado. El diagnóstico temprano reduce la morbilidad y mortalidad de esta complicación.