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.

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.

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.

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.

[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.