strategia di trattamento nelle pancreatiti acute severe

La pancreatite acuta continua ad essere ancora oggi una sfida dal punto di vista clinico, sia diagnostico che terapeutico, ed un problema crescente in Europa e nel mondo in grado di determinare significative conseguenze sia in ambito medico-chirurgico che socio-economico. Si tratta di una patologia caratterizzata da uno spettro molto ampio di alterazioni e lesioni pancreatiche, variabili da un quadro lieve con modesto e transitorio edema del parenchima ghiandolare (75-85% dei casi) ad un quadro severo con alterazioni anatomo-patologiche e cliniche di estrema gravità caratterizzato da emorragie e perdita di vitalità del tessuto pancreatico che va incontro a gangrena e necrosi (15-25% dei casi). Negli ultimi 30 anni la terapia della pancreatite acuta severa è passata da un trattamento esclusivamente chirurgico ad un trattamento sempre più spesso conservativo e multidisciplinare, soprattutto durante la prima fase della sua evoluzione clinica (i primi 10-14 giorni dall’esordio), con indicazione a posticipare l’eventuale intervento chirurgico nella fase successiva dopo l’insorgenza di complicanze emorragiche o settiche non gestibili conservativamente, riservato soprattutto a quei pazienti che presentano infezione della necrosi. Il presente lavoro è consistito nell’analisi retrospettiva delle diverse modalità di trattamento dei casi di pancreatite acuta severa osservati presso il nostro istituto, U.O. Chirurgia Generale 1 dell’Ospedale di Cisanello, nel periodo Agosto 2003-Dicembre 2009

Perfusion machines and hepatocellular carcinoma: a good match between a marginal organ and an advanced disease?

Abstract Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers, is the second leading cause of cancer-related deaths and the leading cause of death in patients with cirrhosis. Liver transplantation (LT) represents the ideal treatment for selected patients as it removes both the tumor and the underlying cirrhotic liver with 5-year survival rates higher than 70%. Unfortunately, due to tumor characteristics, patient co-morbidities or shortage of organs available for transplant, only 20% of patients can undergo curative treatment. Ex situ machine perfusion (MP) is a technology recently introduced that might potentially improve organ preservation, allow graft assessment and increase the pool of available organs. The purpose of this review is to provide an update on the current role of ex situ liver MP in liver transplantation for HCC patients

Colorectal Cancer with Peritoneal Metastases: The Impact of the Results of PROPHYLOCHIP, COLOPEC, and PRODIGE 7 Trials on Peritoneal Disease Management

HIPEC is a potentially useful locoregional treatment combined with cytoreduction in patients with peritoneal colorectal metastases. Despite being widely used in several cancer centers around the world, its role had never been investigated before the results of three important RCTs appeared on this topic. The PRODIGE 7 trial clarified the role of oxaliplatin-based HIPEC in patients treated with radical surgery. Conversely, the PROPHYLOCHIP and the COLOPEC were designed to chair the role of HIPEC in patients at high risk of developing peritoneal metastases. Although all three trials demonstrated the relative ineffectiveness of HIPEC for treating or preventing peritoneal metastases, these results are not sufficient to abandon this technique. In addition to some criticisms relating to the design of the trials and their statistical value, the oxaliplatin-based HIPEC was found to be ineffective in preventing or treating peritoneal colorectal metastases, especially in patients already treated with systemic platinum-based chemotherapy. Several studies are ongoing investigating further HIPEC drugs and regimens. The review deeply discussed all the aspects and relapses of this new evidence

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

Utilizzo di donatori anziani nel trapianto di fegato. Studio monocentrico retrospettivo

INTRODUZIONE L'utilizzo di grafts epatici da donatori anziani permette di aumentare il numero degli organi disponibili per trapianto. Questa pratica non è però universalmente implementata a causa del rischio di insorgenza di potenziali complicanze a breve e lungo termine, in particolare nei riceventi affetti da cirrosi HCV correlata. Al momento, i fattori correlati ad un miglioramento delle sopravvivenze del graft e del paziente non sono stati chiaramente individuati e i dati relativi all'incidenza delle complicanze biliari e dell'arteria epatica sono contraddittori. Studi recenti hanno dimostrato che i donatori anziani possono dare risultati comparabili rispetto ai donatori più giovani se attentamente selezionati, associati a strategie di gestione del donatore e allocazione donatore-ricevente e l'età del donatore non è associata ad ulteriori fattori di rischio. L’adozione di mirate strategie per un'accurata valutazione, selezione e allocazione del graft, nonché la gestione dei grafts anziani prima e dopo il prelievo, potrebbero contribuire ad aumentare il numero dei trapianti mantenendo favorevoli risultati a lungo termine. METODOLOGIA Per conoscere meglio l'esito dei trapianti di fegato utilizzando donatori anziani è stata eseguita un'analisi retrospettiva, paired-match di tutti i trapianti di fegato eseguiti presso il Centro di Chirurgia Epatica e Trapianti di Fegato dell'Università di Pisa da Gennaio 2001 a Dicembre 2014. Sono stati esclusi dall’analisi statistica i donatori di età < 18 anni, i trapianti ABO-incompatibili, i re-trapianti e i trapianti in pazienti in stato clinico UNOS-1. I pazienti sono stati suddivisi in due gruppi in base all’età del donatore: 692 pazienti nel gruppo A (donatore di età tra 18 e 69 anni) e 515 pazienti nel gruppo B (donatore di età superiore a 70 anni). I dati ottenuti sono stati confrontati utilizzando un “propensity score” per le complicanze mediche e chirurgiche post-trapianto e i fattori di rischio associati alla perdita del graft. RISULTATI Il follow-up medio è di 5.0 anni con un range variabile dai 2 agli 8,4 anni. Confrontando i 2 gruppi identificati, non sono state osservate differenze per quanto riguarda l’incidenza di re-trapianti precoci (1,8% vs 2,9%, p=0,3), i decessi HCV-correlati (7,6% vs 8,7%, p=0,6), le complicanze vascolari (5,8% vs 5,0%, p=0,7) e biliari (16,5% vs 18,6%, p=0,4). L'analisi multivariata indipendente ha dimostrato che i fattori di rischio per la perdita del graft sono i seguenti: sierologia HCV-positiva del ricevente (HR=2.1; 95% CI = 1,6-2,7; p <0,001), età del donatore (HR = 1,0; 95% CI = 1,0-1,0; p <0,001), tempo di ischemia fredda (HR = 1,0, 95% CI = 1,0-1,0, p = 0,042) e storia di diabete mellito del donatore (HR = 1,48; 95% CI = 1,03-2,13; p = 0,036). CONCLUSIONE L’età del donatore per sè non è associata ad un incremento dell’incidenza di complicanze vascolari o biliari nel trapianto di fegato. La presenza di storia di diabete mellito nel donatore e il prolungato tempo di ischemia fredda rappresentano fattori di rischio peggiorativi per i risultati soprattutto nei riceventi HCV-positivi, indipendentemente dall’età del donatore. In assenza di tali fattori di rischio i graft dei donatori >70 anni offrono risultati eccellenti in termini di sopravvivenza del graft soprattutto in riceventi HCV-negativi

PILOT STUDY FOR THE EVALUATION OF AN INNOVATIVE DEVICE IN LIVER TRANSPLANTATION USING GRAFTS FROM DONORS AFTER CIRCULATORY DEATH

The Italian law requires 20 minutes of continuous, flat-line electrocardiogram to declare death. In the setting of organ donation after cardio-circulatory death, such prolonged warm ischemia time prompted introduction of abdominal normothermic regional perfusion immediately after death declaration followed by post-procurement, ex-situ machine perfusion. This is a pilot study for the evaluation of an innovative device, such as ex-vivo graft perfusion, subsequently to NRP use in liver transplantation, using grafts from donors after circulatory death.Because of the exploratory characteristics of the present study, no sample size calculation was performed. We had seven recipients receiving grafts from DCD donors after at least 4 hours of ECMO and stored for at least 4 hours in MP before transplantation. We firstly analyzed the data of this group and than compared them with LT with grafts from two different kinds of extended criteria donors in order to valuate the IRI in terms of ITBL, PGD and DGF: a) seven recipients receiving grafts ≥80 years old from DBD donors preserved using the standard static hypothermic method (CS group) and b) seven recipients, from the historical database of our center, receiving grafts from DBD donors who experienced at least 20 minutes of no flow during the 24-48 hours of observation and preserved using the standard static hypothermic method (NF-CS group). The primary endpoint of the study is the evaluation of the preservation efficacy of ex-vivo MP following the NRP (ECMO) in LT performed using DCD donors by means of graft and patient survival 6 months after liver transplantation. The secondary endpoint was to evaluate IRI by means of post LT transaminases after surgery, evaluation of liver and bile duct histology and incidence of biliary complications after 6 months from transplantation

Perfusion machines and hepatocellular carcinoma: A good match between a marginal organ and an advanced disease?

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers, is the second leading cause of cancer-related deaths and the leading cause of death in patients with cirrhosis. Liver transplantation (LT) represents the ideal treatment for selected patients as it removes both the tumor and the underlying cirrhotic liver with 5-year survival rates higher than 70%. Unfortunately, due to tumor characteristics, patient co-morbidities or shortage of organs available for transplant, only 20% of patients can undergo curative treatment. Ex situ machine perfusion (MP) is a technology recently introduced that might potentially improve organ preservation, allow graft assessment and increase the pool of available organs. The purpose of this review is to provide an update on the current role of ex situ liver MP in liver transplantation for HCC patients

Use of elderly donors in liver transplantation. A paired-match analysis at a single center

OBJECTIVE: To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome. SUMMARY BACKGROUND DATA: Use of livers from very old donors could expand the donor pool but is not universally implemented. METHODS: This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18-69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases). RESULTS: The median (interquartile range [IQR]) follow-up was 5.0 (2.0-8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6-2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0-1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0-1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03-2.13; P = 0.036). CONCLUSIONS: Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted

Machine perfusions in liver transplantation: The evidence-based position paper of the italian society of organ and tissue transplantation.

BACKGROUND AND AIMS The use of machine perfusion in liver transplantation is spreading worldwide but its efficacy has not been demonstrated and its proper clinical use far to be implemented. The Italian Society of Organ and Tissue Transplantation (SITO) promoted the development of an evidence-based position paper. METHODS A three-step approach has been adopted to develop this position paper. Firstly, the Society appointed a Chair and a co-Chair who then assembled a Working Group with specific experience of machine perfusion in liver transplantation. The Guideline Development Group framed the clinical questions into a Patient/Intervention/Control/Outcome (PICO) format, extracted and analyzed available literature, ranked the quality of evidence, prepared and graded the recommendations. Recommendations were then discussed by all the members of the SITO and voted by Delphi round by an Internal Review Board and finally evaluated and scored by a panel of external reviewers. RESULTS All available literature was analyzed, and its quality ranked. Eighteen recommendations regarding the use and the efficacy of ex-situ hypothermic and normothermic machine perfusion and sequential normothermic regional perfusion and ex-situ machine perfusion were prepared and graded according to the GRADE method. CONCLUSION A critical and scientific approach is required for the safe implementation of this new technology

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design