Publications by authors named "Michele Colledan"

79 Publications

Arterioportal Fistulas (APFs) in Pediatric Patients: Single Center Experience with Interventional Radiological versus Conservative Management and Clinical Outcomes.

J Clin Med 2021 Jun 14;10(12). Epub 2021 Jun 14.

Department of Radiology, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy.

Arterioportal fistulas (APFs) are uncommon vascular abnormalities with a heterogeneous etiology. In pediatric orthotopic liver transplantation (OLT), APFs are frequently iatrogenic, following percutaneous liver interventions. The aim of this study was to report the 10-year experience of a tertiary referral center for pediatric OLT in the interventional radiological (IR) and conservative management of acquired APFs. A retrospective search was performed to retrieve pediatric patients (<18 years old) with a diagnosis of APF at color Doppler ultrasound (CDUS) or computed tomography angiography (CTA) from 2010 to 2020. Criteria for IR treatment were the presence of hemodynamic alterations at CDUS (resistive index <0.5; portal flow reversal) or clinical manifestations (bleeding; portal hypertension). Conservatively managed patients served as a control population. Clinical and imaging follow-up was analyzed. Twenty-three pediatric patients (median age, 4 years; interquartile range = 11 years; 15 males) with 24 APFs were retrieved. Twenty patients were OLT recipients with acquired APFs (16 iatrogenic). Twelve out of twenty-three patients were managed conservatively. The remaining 11 underwent angiography with confirmation of a shunt in 10, who underwent a total of 16 embolization procedures (14 endovascular; 2 transhepatic). Technical success was reached in 12/16 (75%) procedures. Clinical success was achieved in 8/11 (73%) patients; three clinical failures resulted in one death and two OLTs. After a median follow-up time of 42 months (range 1-107), successfully treated patients showed an improvement in hemodynamic parameters at CDUS. Conservatively managed patients showed a stable persistence of the shunts in six cases, spontaneous resolution in four, reduction in one and mild shunt increase in one. In pediatric patients undergoing liver interventions, APFs should be investigated. Although asymptomatic in most cases, IR treatment of APFs should be considered whenever hemodynamic changes are found at CDUS.
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http://dx.doi.org/10.3390/jcm10122612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231897PMC
June 2021

Long-Term Outcomes of Kidney Transplants from Older/Marginal Donors: A Cohort Study.

Nephron 2021 Jun 15:1-11. Epub 2021 Jun 15.

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Introduction: To safely expand the donor pool, we introduced a strategy of biopsy-guided selection and allocation to single or dual transplantation of kidneys from donors >60 years old or with hypertension, diabetes, and/or proteinuria (older/marginal donors). Here, we evaluated the long-term performance of this approach in everyday clinical practice.

Methods: In this single-center cohort study, we compared outcomes of 98 patients who received one or two biopsy-evaluated grafts from older/marginal donors ("recipients") and 198 patients who received nonhistologically assessed single graft from ideal donors ("reference-recipients") from October 2004 to December 2015 at the Bergamo Transplant Center (Italy).

Results: Older/marginal donors and their recipients were 27.9 and 19.3 years older than ideal donors and their reference-recipients, respectively. KDPI/KDRI and donor serum creatinine were higher and cold ischemia time longer in the recipient group. During a median follow-up of 51.9 (interquartile range 23.1-88.6) months, 11.2% of recipients died, 7.1% lost their graft, and 16.3% had biopsy-proven acute rejection (BPAR) versus 3.5, 7.6, and 17.7%, respectively, of reference-recipients. Overall death-censored graft failure (rate ratio 0.78 [95% CI 0.33-2.08]), 5-year death-censored graft survival (94.3% [87.8-100.0] vs. 94.2% [90.5-98.0]), BPAR incidence (rate ratio 0.87 [0.49-1.62]), and yearly measured glomerular filtration rate decline (1.18 ± 3.27 vs. 0.68 ± 2.42 mL/min/1.73 m2, p = 0.37) were similar between recipients and reference-recipients, respectively.

Conclusions: Biopsy-guided selection and allocation of kidneys from older/marginal donors can safely increase transplant activity in clinical practice without affecting long-term outcomes. This may help manage the growing gap between organ demand and supply without affecting long-term recipient and graft outcomes.
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http://dx.doi.org/10.1159/000516534DOI Listing
June 2021

Post-operative heparin reduces early venous thrombotic complications after orthotopic paediatric liver transplantation.

Blood Transfus 2021 Mar 12. Epub 2021 Mar 12.

Department of Immunohaematology and Transfusion Medicine, "Papa Giovanni XXIII" Hospital, Bergamo, Italy.

Background: Despite significant improvements in surgical techniques and medical care, thrombotic complications still represent the primary cause of early graft failure and re-transplantation following paediatric liver transplantation. There is still no standardized approach for thrombosis prevention.

Materials And Methods: The study aimed to evaluate the effectiveness of early intravenous unfractionated heparin started 12 hours postoperatively at 10 UI/kg per hour and used a retrospective "before and after" design to compare the incidence of early thrombotic complications prior to (2002-2010) and after (2011-2016) the introduction of heparin in our institute.

Results: From 2002 to 2016, 479 paediatric patients received liver transplantation in our institution with an overall survival rate over one year of 0.91 (95% CI: 0.87-0.94). Of 365 eligible patients, 244 did not receive heparin while 121 did receive heparin. We reported a lower incidence of venous thrombosis (VT) in the group treated with heparin: 2.5% (3/121) vs 7.9% (19/244) (p=0.038). All clinical and laboratory variables considered potential risk factors for VT were studied. By multivariate stepwise Cox proportional hazards models, heparin prophylaxis resulted significantly associated to a reduction in VT (HR=0.29 [95% CI: 0.08-0.97], p=0.045), while age <1 year was found to be an independent risk factor for VT (HR=2.62 [95% CI: 1.11-6.21]; p=0.028).

Discussion: Early postoperative heparin could be considered a valid and safe strategy to prevent early VT after paediatric liver transplantation without a concomitant increase in bleeding. A future randomised control trial is mandatory in order to strengthen this conclusion.
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http://dx.doi.org/10.2450/2021.0388-20DOI Listing
March 2021

An Italian survey on the use of T-tube in liver transplantation: old habits die hard!

Updates Surg 2021 Apr 1. Epub 2021 Apr 1.

Liver-Kidney Transplantation Unit, Department of Medicine, University of Udine, Udine, Italy.

There is enough clinical evidence that a T-tube use in biliary reconstruction at adult liver transplantation (LT) does not significantly modify the risk of biliary stricture/leak, and it may even sustain infective and metabolic complications. Thus, the policy on T-tube use has been globally changing, with progressive application of more restrictive selection criteria. However, there are no currently standardized indications in such change, and many LT Centers rely only on own experience and routine. A nation-wide survey was conducted among all the 20 Italian adult LT Centers to investigate the current policy on T-tube use. It was found that 20% of Centers completely discontinued the T-tube use, while 25% Centers used it routinely in all LT cases. The remaining 55% of Centers applied a selective policy, based on criteria of technical complexity of biliary reconstruction (72.7%), followed by low-quality graft (63.6%) and high-risk recipient (36.4%). A T-tube use > 50% of annual caseload was not associated with high-volume Center status (> 70 LT per year), an active pediatric or living-donor transplant program, or use of DCD grafts. Only 10/20 (50%) Centers identified T-tube as a potential risk factor for complications other than biliary stricture/leak. In these cases, the suspected pathogenic mechanism comprised bacterial colonization (70%), malabsorption (70%), interruption of the entero-hepatic bile-acid cycle (50%), biliary inflammation due to an indwelling catheter (40%) and gut microbiota changes (40%). In conclusion, the prevalence of T-tube use among the Italian LT Centers is still relatively high, compared to the European trend (33%), and the potential detrimental effect of T-tube, beyond biliary stricture/leak, seems to be somehow underestimated.
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http://dx.doi.org/10.1007/s13304-021-01019-1DOI Listing
April 2021

Covid-19 and gender: lower rate but same mortality of severe disease in women-an observational study.

BMC Pulm Med 2021 Mar 20;21(1):96. Epub 2021 Mar 20.

Department of Health and Social Care Professions, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients.

Methods: Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization.

Results: 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO/FiO was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687).

Conclusion: Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.
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http://dx.doi.org/10.1186/s12890-021-01455-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980742PMC
March 2021

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion.

Transplantation 2021 Jan 7. Epub 2021 Jan 7.

1. Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy. 2. Liver Unit, Queen Elizabeth University Hospital Birmingham, Birmingham, UK. 3. Department of Statistics and Quantitative Methods, University of Milan-Bicocca, Milan, Italy. 4. Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit, University of Modena and Reggio Emilia, Modena, Italy. 5. UO Chirurgia Generale e dei Trapianti, AOU Sant'Orsola-Malpighi, Alma Mater Studiorum Università di Bologna, Bologna, Italy. 6. Division of Liver Transplantation, AO Papa Giovanni XXIII, Bergamo, Italy. 7. General Surgery 2U, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy. 8. Department of Surgery, Oncology and Gastroenterology, Hepatobiliary Surgery and Liver Transplant Unit, Padua University, Padua, Italy. 9. Abdominal Surgery and Organ Transplantation Unit, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS - ISMETT), Palermo, Italy 10. Hepatobiliary Unit, Careggi University Hospital, University of Florence, Florence, Italy 11. Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.

Background: Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE).

Methods: We coordinated a multicenter retrospective Italian cohort study with 44 controlled DCD donors, who underwent NRP, to present transplant characteristics and results. To rank our results according to the high donor risk, we matched and compared a subgroup of 37 controlled DCD livers, preserved with NRP and D-HOPE, with static-preserved controlled DCD transplants from an established European program.

Results: In the Italian cohort, D-HOPE was used in 84% of cases, and the primary nonfunction rate was 5%. Compared to the matched comparator group, the NRP+D-HOPE-group showed a lower incidence of moderate and severe acute kidney injury (stage 2: 8% vs 27% and stage 3: 3% vs 27%, P=0.001). Ischemic cholangiopathy remained low (2-year proportion free: 97% vs 92%, P=0.317), despite the high-risk profile resulting from the longer donor warm ischemia in Italy (40 vs 18min, P<0.001).

Conclusions: These data suggest that NRP and D-HOPE yield good results in DCD livers with prolonged warm ischemia.
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http://dx.doi.org/10.1097/TP.0000000000003595DOI Listing
January 2021

Hepatic hemangioendothelioma of infancy: clinical features of a large cohort of patients and proposed management.

Pediatr Surg Int 2021 Jun 29;37(6):791-797. Epub 2021 Jan 29.

Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII di Bergamo, Piazza OMS1, 24127, Bergamo, Italy.

Purpose: The management of hepatic hemangioendothelioma (HHE) may be challenging. We aimed to review a large cohort of children who presented to our centers with symptomatic HHE in the last 16 years.

Methods: We collected age at presentation, clinical features, histology, diagnostic process, management and outcome.

Results: Twenty seven patients (male/female 5/22), median age 13 days (1-1530) presented with hepatomegaly (24/27), cardiac failure (10/27), cutaneous hemangiomas (8/27), fever and anemia (6/27 each), vomiting (5/27), splenomegaly (4/27). The lesion was focal, multifocal, or diffuse in 9 patients of each group. The management included medical treatment (8/27), embolization (8/27), resection (3/27), observation (6/27), transplantation (2/27). After 16 months' follow-up (30 days-11 years), 23/27 (85%) were alive. Diffuse lesions (4/4), cardiac failure (4/4), type II histology (4/4), age older than 6 months at diagnosis (3/4) predicted mortality (all p < 0.01). Histology showed type 1 lesion in 3/8, type 2 in 3/8, and type 3 in 2/8 with foci of angiosarcoma.

Conclusion: Most patients with symptomatic HHE can be managed successfully with a combination of medical, radiological and surgical treatments. Patients with diffuse lesions, late presentation, cardiac failure and type II histology have a poor outcome.

Level Of Evidence: Diagnostic level IV. Therapeutic level IV.
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http://dx.doi.org/10.1007/s00383-021-04860-yDOI Listing
June 2021

Third-party bone marrow-derived mesenchymal stromal cell infusion before liver transplantation: A randomized controlled trial.

Am J Transplant 2020 Dec 28. Epub 2020 Dec 28.

Aldo & Cele Daccò Clinical Research Center for Rare Diseases, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Mesenchymal stromal cells (MSC) have emerged as a promising therapy to minimize the immunosuppressive regimen or induce tolerance in solid organ transplantation. In this randomized open-label phase Ib/IIa clinical trial, 20 liver transplant patients were randomly allocated (1:1) to receive a single pretransplant intravenous infusion of third-party bone marrow-derived MSC or standard of care alone. The primary endpoint was the safety profile of MSC administration during the 1-year follow-up. In all, 19 patients completed the study, and none of those who received MSC experienced infusion-related complications. The incidence of serious and non-serious adverse events was similar in the two groups. Circulating Treg/memory Treg and tolerant NK subset of CD56 NK cells increased slightly over baseline, albeit not to a statistically significant extent, in MSC-treated patients but not in the control group. Graft function and survival, as well as histologic parameters and intragraft expression of tolerance-associated transcripts in 1-year protocol biopsies were similar in the two groups. In conclusion, pretransplant MSC infusion in liver transplant recipients was safe and induced mild positive changes in immunoregulatory T and NK cells in the peripheral blood. This study opens the way for a trial on possible tolerogenic efficacy of MSC in liver transplantation. ClinicalTrials.gov identifier: NCT02260375.
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http://dx.doi.org/10.1111/ajt.16468DOI Listing
December 2020

At the peak of COVID-19 age and disease severity but not comorbidities are predictors of mortality: COVID-19 burden in Bergamo, Italy.

Panminerva Med 2021 Mar 27;63(1):51-61. Epub 2020 Nov 27.

Unit of Quality Management, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Findings from February 2020, indicate that the clinical spectrum of COVID-19 can be heterogeneous, probably due to the infectious dose and viral load of SARS-CoV-2 within the first weeks of the outbreak. The aim of this study was to investigate predictors of overall 28-day mortality at the peak of the Italian outbreak.

Methods: Retrospective observational study of all COVID-19 patients admitted to the main hospital of Bergamo, from February 23 to March 14, 2020.

Results: Five hundred and eight patients were hospitalized, predominantly male (72.4%), mean age of 66±15 years; 49.2% were older than 70 years. Most of patients presented with severe respiratory failure (median value [IQR] of PaO2/FiO2: 233 [149-281]). Mortality rate at 28 days resulted of 33.7% (N.=171). Thirty-nine percent of patients were treated with continuous positive airway pressure (CPAP), 9.5% with noninvasive ventilation (NIV) and 13.6% with endotracheal intubation. 9.5% were admitted to Semi-Intensive Respiratory Care Unit, and 18.9% to Intensive Care Unit. Risk factors independently associated with 28-day mortality were advanced age (≥78 years: odds ratio [OR], 95% confidence interval [CI]: 38.91 [10.67-141.93], P<0.001; 70-77 years: 17.30 [5.40-55.38], P<0.001; 60-69 years: 3.20 [1.00-10.20], P=0.049), PaO2/FiO2<200 at presentation (3.50 [1.70-7.20], P=0.001), need for CPAP/NIV in the first 24 hours (8.38 [3.63-19.35], P<0.001), and blood urea value at admission (1.01 [1.00-1.02], P=0.015).

Conclusions: At the peak of the outbreak, with a probable high infectious dose and viral load, older age, the severity of respiratory failure and renal impairment at presentation, but not comorbidities, are predictors of 28-day mortality in COVID-19.
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http://dx.doi.org/10.23736/S0031-0808.20.04063-XDOI Listing
March 2021

Endoluminal vacuum-assisted closure (E-Vac) therapy for postoperative esophageal fistula: successful case series and literature review.

World J Surg Oncol 2020 Nov 14;18(1):301. Epub 2020 Nov 14.

General Surgery III, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: Treatment of esophageal perforations and postoperative anastomotic leaks of the upper gastrointestinal tract remains a challenge. Endoluminal vacuum-assisted closure (E-Vac) therapy has positively contributed, in recent years, to the management of upper gastrointestinal tract perforations by using the same principle of vacuum-assisted closure therapy of external wounds. The aim is to provide continuous wound drainage and to promote tissue granulation, decreasing the needed time to heal with a high rate of leakage closure.

Cases Presentation: A series of two different cases with clinical and radiological diagnosis of esophageal fistulas, recorded from 2018 to 2019 period at our institution, is presented. The first one is a case of anastomotic leak after esophagectomy for cancer complicated by pleuro-mediastinal abscess, while the second one is a leak of an esophageal suture, few days after resection of a bronchogenic cyst perforated into the esophageal lumen. Both cases were successfully treated with E-Vac therapy.

Conclusion: Our experience shows the usefulness of E-Vac therapy in the management of anastomotic and non-anastomotic esophageal fistulas. Further research is needed to better define its indications, to compare it to traditional treatments and to evaluate its long-term efficacy.
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http://dx.doi.org/10.1186/s12957-020-02073-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666449PMC
November 2020

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure Among Patients Requiring Early Liver Retransplant.

JAMA Surg 2020 12 16;155(12):e204095. Epub 2020 Dec 16.

S. Orsola-Malpighi University Hospital, Bologna, Italy.

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015.

Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant.

Design, Setting, And Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017.

Main Outcomes And Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant.

Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk.

Conclusions And Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers.
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http://dx.doi.org/10.1001/jamasurg.2020.4095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593884PMC
December 2020

Minimally Invasive Stage 1 to Protect Against the Risk of Liver Failure: Results from the Hepatocellular Carcinoma Series of the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy Italian Registry.

J Laparoendosc Adv Surg Tech A 2020 Oct 9;30(10):1082-1089. Epub 2020 Sep 9.

Department of General Surgery, Azienda Ospedaliero-Universitaria di Bologna, Maggiore Hospital, Bologna, Italy.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been described to treat hepatocellular carcinoma (HCC) but burdened, in its pioneering phase, by high morbidity and mortality. With the advent of minimally invasive (MI) techniques in liver surgery, surgical complications, including posthepatectomy liver failure (PHLF), have been dramatically reduced. The primary endpoint of this study was to compare the short-term outcomes of MI- versus open-ALPPS for HCC, with specific focus on PHLF. Data of patients submitted to ALPPS for HCC between 2012 and 2020 were identified from the ALPPS Italian Registry. Patients receiving an MI Stage 1 (MI-ALPPS) constituted the study group, whereas the patients who received an open Stage 1 (open-ALPPS) constituted the control group. Sixty-six patients were enrolled from 12 Italian centers. Stage 1 of ALPPS was performed in 14 patients using an MI approach (21.2%). MI-ALPPS patients were discharged after Stage 1 at a significantly higher rate compared with open-ALPPS (78.6% versus 9.6%,  < .001). After Stage 2, major morbidity after MI-ALPPS was 8.3% compared with 28.6% reported after open-ALPPS. Mortality was nil after MI-ALPPS. Length of hospital stay was significantly shorter in MI-ALPPS (12 days versus 22 days,  < .001). Univariate logistic regression analysis (Firth method) found that both MI-ALPPS (odds ratio [OR] = 0.05,  = .040) and partial parenchymal transection (OR = 0.04,  = .027) were protective against PHLF. This national multicenter study showed that a less invasive approach to ALPPS first stage was associated with a lower overall risk of PHLF.
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http://dx.doi.org/10.1089/lap.2020.0563DOI Listing
October 2020

mTOR Inhibition Is Most Beneficial After Liver Transplantation for Hepatocellular Carcinoma in Patients With Active Tumors.

Ann Surg 2020 11;272(5):855-862

CHRU de Montpellier, APEMAD, Hôpital Saint-Eloi, Service d'Hepato-Gastroentérologie et Transplantation Hepatique, Cedex 5, France.

Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial).

Summary And Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data.

Patients And Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence.

Results: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245).

Conclusions: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients.

Clinical Trial Registration: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.
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http://dx.doi.org/10.1097/SLA.0000000000004280DOI Listing
November 2020

Health related quality of life in chronic liver diseases.

Liver Int 2020 11;40(11):2630-2642

Research Centre on Public Health (CESP), University of Milan-Bicocca, Milan, Italy.

Background & Aims: The impact of chronic liver diseases (CLDs) on health-related quality of life (HRQoL) is relevant to understand the burden of these conditions and inform decision-making processes related to their care. Studies simultaneously comparing the HRQoL of patients affected by the major CLDs to that of the general population are still lacking and are the subject of this study.

Methods: Using the EQ-5D-3L questionnaire, we analysed and compared HRQoL data from 2962 Italian patients affected by CLDs and forming a representative sample of the general Italian population (6800 individuals). Exploratory analyses were conducted to investigate the effects of each CLD on HRQoL, using the general population as reference and adjusting for possible confounders.

Results: Patients with CLDs (HBV, HCV, PSC, PBC, AIH, NAFLD/NASH) in the chronic hepatitis stage and with compensated cirrhosis (CC) showed HRQoL similar to the general population. However, AIH were more likely to report problems in self-care and lower EQ-5D VAS score, while NAFLD/NASH and HCV showed an increased risk of anxiety/depression. On the other hand, with progression to more advanced stages of liver disease (DC or HCC), HRQoL decreased significantly with higher risk of reporting problems in the physical domains, and significant reductions in the VAS and utility index scores.

Conclusions: Different subtypes of CLD affected different QoL domains. This study therefore provides a real estimate of the impact of CLDs on patients' HRQoL, and represents a much needed tool to inform decision-making while assessing the effectiveness and cost-effectiveness of the care of these patients.
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http://dx.doi.org/10.1111/liv.14647DOI Listing
November 2020

Subclinical biliary strictures as a cause of long-term allograft dysfunction in children who underwent liver transplantation.

Am J Transplant 2021 01 8;21(1):391-399. Epub 2020 Sep 8.

Paediatric Hepatology, Gastroenterology and Transplantation, Hospital Papa Giovanni XXIII, Bergamo, Italy.

We aimed to evaluate the role of liver biopsy to predict subclinical biliary strictures (BS) and assess the impact of BS on long-term allograft dysfunction following liver transplantation in children (LT). We reviewed all liver biopsies performed from 2012-2018. Percutaneous transhepatic cholangiography (PTC) was performed in patients presenting cholangiolar proliferation on cytokeratin-7 stained sections. We performed 271 biopsies in 161 children (86% with a left lateral segment); 44/161 (27%) presented with diffuse or multifocal cholangiolar proliferation. Among them, a tight BS was confirmed in 38/44 (86%, 24% of total) and it was managed by balloon dilatation. Cholangiolar proliferation showed a positive predictive value (PPV) for BS of 86.4%. Levels of alkaline phosphatase >325 IU/L predicted BS (P = .007). Dilatation of intrahepatic bile ducts on ultrasound was found only in 44% of patients with BS. Following a median follow-up of 9.2 years, only 15/38 (39%) patients resolved the BS. In conclusion subclinical BS is very common and probably underdiagnosed in these patients. Histological evidence of cholangiolar proliferation detectable by cytokeratin-7 immunostain should be preferred to liver function tests and ultrasound to suspect BS. BS in this setting should be regarded as a main cause of long-term allograft dysfunction.
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http://dx.doi.org/10.1111/ajt.16270DOI Listing
January 2021

Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.

Lancet Oncol 2020 07;21(7):947-956

HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.

Background: Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging.

Methods: We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18-65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov, NCT01387503.

Findings: Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4-11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60-85). 5-year tumour event-free survival was 76·8% (95% CI 60·8-96·9) in the transplantation group versus 18·3% (7·1-47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07-0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9-97·1) in the transplantation group versus 31·2% (16·6-58·5) in the control group (HR 0·32, 95% CI 0·11-0·92; p=0·035). The most common registered grade 3-4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation).

Interpretation: Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria.

Funding: Italian Ministry of Health.
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http://dx.doi.org/10.1016/S1470-2045(20)30224-2DOI Listing
July 2020

The impact of the COVID-19 outbreak on liver transplantation programs in Northern Italy.

Am J Transplant 2020 Jul 22;20(7):1840-1848. Epub 2020 May 22.

Transplant Coordination Reference Center - North Italy Transplant program (CRR/NITp), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.

In January 2020, Novel Coronavirus Disease 2019 (COVID-19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID-19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18-74) whereas mean recipient age was 55 (13-69); mean MELD score was 12 (6-24). All donors underwent screening for SARS-CoV-2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post-LT (range 3-46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement.
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http://dx.doi.org/10.1111/ajt.15948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264498PMC
July 2020

Clinical outcome indicators in chronic hepatitis B and C: A primer for value-based medicine in hepatology.

Liver Int 2020 01 12;40(1):60-73. Epub 2019 Nov 12.

International Center for Digestive Health, University of Milan-Bicocca, Milan, Italy.

Background & Aims: Chronic liver diseases (CLDs) are major health problems that require complex and costly treatments. Liver-specific clinical outcome indicators (COIs) able to assist both clinicians and administrators in improving the value of care are presently lacking. The Value-Based Medicine in Hepatology (VBMH) study aims to fill this gap, devising and testing a set of COIs for CLD, that could be easily collected during clinical practice. Here we report the COIs generated and recorded for patients with HBV or HCV infection at different stages of the disease.

Methods/results: In the first phase of VBMH study, COIs were identified, based on current international guidelines and literature, using a modified Delphi method and a RAND 9-point appropriateness scale. In the second phase, COIs were tested in an observational, longitudinal, prospective, multicentre study based in Lombardy, Italy. Eighteen COIs were identified for HBV and HCV patients. Patients with CLD secondary to HBV (547) or HCV (1391) were enrolled over an 18-month period and followed for a median of 4 years. The estimation of the proposed COIs was feasible in the real-word clinical practice and COI values compared well with literature data. Further, the COIs were able to capture the impact of new effective treatments like direct-acting antivirals (DAAs) in the clinical practice.

Conclusions: The COIs efficiently measured clinical outcomes at different stages of CLDs. While specific clinical practice settings and related healthcare systems may modify their implementation, these indicators will represent an important component of the tools for a value-based approach in hepatology and will positively affect care delivery.
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http://dx.doi.org/10.1111/liv.14285DOI Listing
January 2020

Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study.

Transplantation 2019 09;103(9):1844-1862

Department of Surgery and Liver Transplantation, Fundeni Clinical Institute, University of Medicine "Carol Davila", Bucharest, Romania.

Background: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study.

Methods: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T. Overall, 13 088 patients were included from 44 European centers; propensity score-matched analyses comprised 3006 patients (PR-T: n = 1002; IR-T: n = 2004).

Results: In multivariate analyses, IR-T-based immunosuppression was associated with reduced graft survival (risk ratio, 1.49; P = 0.0038) and patient survival (risk ratio, 1.40; P = 0.0215). There was improvement with PR-T versus IR-T in graft survival (83% versus 77% at 4 y, respectively; P = 0.005) and patient survival (85% versus 80%; P = 0.017). Patients converted from IR-T to PR-T after 1 month had a higher graft survival rate than patients receiving IR-T at last follow-up (P < 0.001), or started and maintained on PR-T (P = 0.019). One graft loss in 4 years was avoided for every 14.3 patients treated with PR-T versus IR-T.

Conclusions: PR-T-based immunosuppression might improve long-term outcomes in liver transplant recipients than IR-T-based immunosuppression.
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http://dx.doi.org/10.1097/TP.0000000000002700DOI Listing
September 2019

Successful preservation and transplant of warm ischaemic lungs from controlled donors after circulatory death by prolonged in situ ventilation during normothermic regional perfusion of abdominal organs.

Interact Cardiovasc Thorac Surg 2019 11;29(5):699-705

Thoracic Surgery and Lung Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Objectives: Donation after circulatory death (DCD) potentially provides transplantable lungs suitable for a transplant, but in Italy, the need for 20 min of a no-touch period after cardiac arrest for legal declaration of death poses real challenges to organ preservation.

Methods: This is a single-institution, retrospective study using data collected prospectively between October and December 2017. After the approval of the multidisciplinary DCD study group of Regione Lombardia, Maastricht category III DCD donors became eligible for combined procurement of lungs and abdominal organs. Our group subsequently established a dedicated technical protocol. Our protocol consists of a non-rapid normothermic open-lung procurement process that takes place during abdominal normothermic regional perfusion, namely without pleural topical cooling before the start of pneumoplegia. After the lung is procured according to the technique described in the article, lung function is evaluated by ex vivo lung perfusion, which is run with the low-flow, open atrium, low haematocrit technique.

Results: During the study, we managed 5 controlled DCDs. In 3 cases, the lungs were successfully transplanted. All 3 patients are alive after 1 year, with good respiratory function.

Conclusions: Our approach resulted in adequate lung preservation and successful transplants without detrimental effects on abdominal organ procurement, confirming the possibility of overcoming the obstacle of a long no-touch period in a DCD setting.
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http://dx.doi.org/10.1093/icvts/ivz160DOI Listing
November 2019

Early post-liver transplant surgical morbidity in HIV-infected recipients: risk factor for overall survival? A nationwide retrospective study.

Transpl Int 2019 Oct 27;32(10):1044-1052. Epub 2019 May 27.

Liver-Kidney Transplant Unit, ASUIUD, Udine, Italy.

The aim of the study was to analyse the risk factors for early surgical complications requiring relaparotomy and the related impact on overall survival (OS) in HIV-infected patients submitted to liver transplantation. Thus a retrospective investigation was conducted on a nationwide multicentre cohort of 157 HIV patients submitted to liver transplantation in six Italian Transplant Units between 2004 and 2014. An early relaparotomy was performed in 24.8% of cases and the underlying clinical causes were biliary leak (8.2%), bleeding (8.2%), intestinal perforation (4.5%) and suspect of vascular complications(3.8%). No differences in terms of prevalence for either overall or cause-specific early relaparotomies were noted when compared with a non-HIV control group, matched for MELD, recipient age, HCV-RNA positivity and HBV prevalence. While in the control group an early relaparotomy appeared a negative prognostic factor, such impact on OS was not noted in HIV recipients. Nonetheless increasing number of relaparotomies were associated with decreased survival. In multivariate analysis, preoperative refractory ascites and Roux-en-Y choledochojejunostomy reconstruction were significant risk factors for early relaparotomy. To conclude, in HIV liver transplanted patients, an increasing number of early relaparotomies because of surgical complications does negatively affect the OS. Preoperative refractory ascites reflecting a severe portal hypertension and a difficult biliary tract reconstruction requiring a Roux-en-Y choledochojejunostomy are associated with increased risk of early relaparotomy.
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http://dx.doi.org/10.1111/tri.13446DOI Listing
October 2019

A national mandatory-split liver policy: A report from the Italian experience.

Am J Transplant 2019 07 14;19(7):2029-2043. Epub 2019 Mar 14.

Italian National Transplant Center, Italian National Institute of Health, Rome, Italy.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially "splittable" donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P = .009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P = .045]). The pediatric (4.5% vs 2.5% [P = .398]) and adult (9.7% to 5.2% [P < .001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P = .035) and recipient weight >20 kg (HR = 5.113, P = .048) in LLS, and ischemic time >8 hours (HR = 2.475, P = .048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.
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http://dx.doi.org/10.1111/ajt.15300DOI Listing
July 2019

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Liver Transpl 2019 02;25(2):242-251

Dipartimento di Chirurgia Generale e Trapianti d'Organo, Policlinico, Universitario Agostino Gemelli, Rome, Italy.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.
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http://dx.doi.org/10.1002/lt.25400DOI Listing
February 2019

2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation.

Transpl Int 2018 12;31(12):1293-1317

University of Edinburgh Royal Infirmary, Edinburgh, UK.

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.
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http://dx.doi.org/10.1111/tri.13358DOI Listing
December 2018

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian and gastrointestinal peritoneal carcinomatosis: results from a 7-year experience.

J Gastrointest Oncol 2018 Apr;9(2):241-253

Unit of General and Emergency Surgery, ASST Papa Giovanni XXIII, Bergamo, Italy.

Background: An increasing promising evidence and increasing long-term oncologic outcomes support the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as locoregional treatment for peritoneal carcinosis (PC) especially from ovarian and gastrointestinal tumors, but also for others cancers.

Methods: A prospective monocentric study was performed in Papa Giovanni XXIII Hospital, Bergamo (Italy). Patients and tumor characteristics were analyzed. Overall survival (OS), disease free survival (DFS) and morbidity were analyzed with Kaplan-Meier curves and log-rank testing.

Results: A total of 150 patients undergone CRS + HIPEC were analyzed from January 2011 to June 2017. The principal origins of PC were: gastric cancer (GC) (n=40), colon cancer (n=31), appendiceal cancer (AC) (n=18), ovarian cancer (OC) (n=49), others (n=12). Major morbidity [≥3 Common Terminology Criteria for Adverse Events (CTCAE)] and perioperative mortality rates were 38% and 2.7% respectively. Re-operation rate was 15.3%. Median OS is 9, 35, 47, 51, 82 months (29% 3-year OS; 27% 5-year OS; 48% 5-year OS; 40% 5-year OS; 67% 5-year OS respectively) in GC, colorectal cancer (CRC), OC, others tumors and AC respectively. Median DFS is 4, 14, 17, 19, 82 months (32% 3-year DFS; 22% 5-year DFS; 29% 5-year DFS; 11% 5-year DFS; 67% 5-year DFS respectively) in GC, CRC, others tumors, OC and AC respectively.

Conclusions: A therapeutic approach that combined CRS + HIPEC could achieve long-term survival in selected groups of patients with PC from gastrointestinal, gynecological and others tumors with acceptable morbidity and mortality. A good expertise and a high volume of patients are necessary to manage PC and to further improve results.
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http://dx.doi.org/10.21037/jgo.2017.12.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934148PMC
April 2018

Treatment of hepatocellular carcinoma: a cost analysis of yttrium-90 transarterial radioembolization versus sorafenib.

Future Oncol 2018 Apr 26;14(8):727-735. Epub 2018 Mar 26.

Gastroenterology 1 - Hepatology & Transplantology, ASST Papa Giovanni XXIII, Piazza OMS - Organizzazione Mondiale della Sanità 1, 24127 Bergamo, Italy.

Aim: The aim was to evaluate cost-effectiveness of yttrium-90 transarterial radioembolization (TARE) in comparison to sorafenib treatment.

Patients & Methods: A single-center, retrospective, observational study was performed, 166 patients with intermediate-/advanced-stage hepatocellular carcinoma were treated with sorafenib and 19 with TARE. The patients out of the sorafenib group matching the inclusion criteria for TARE, were reassigned to a subgroup SOR3.

Results: Mean costs for SOR3 patients amounted to €27,992 per patient, instead for TARE treatment, mean expense per patient was €17,761 (p = 0.028). Overall survival was similar between the two groups, while midterm survival rates (p = 0.012) were significantly higher with TARE treatment.

Conclusion: TARE causes significantly lower treatment costs than sorafenib with better outcome in midterm survival.
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http://dx.doi.org/10.2217/fon-2017-0566DOI Listing
April 2018

Higher retransplantation rate following extended right split-liver transplantation: An analysis from the eurotransplant liver follow-up registry.

Liver Transpl 2018 06 13;24(6):849-850. Epub 2018 May 13.

Division of Abdominal Transplantation and Hepatobiliopancreatic Surgery, Bambino Gesù Children's Research Hospital Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.

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http://dx.doi.org/10.1002/lt.25035DOI Listing
June 2018

Value of HCC-MELD Score in Patients With Hepatocellular Carcinoma Undergoing Liver Transplantation.

Prog Transplant 2018 03 18;28(1):63-69. Epub 2017 Dec 18.

2 Department of Surgery, General surgery and Abdominal Transplant unit, "Papa Giovanni XXIII" Hospital, Bergamo, Italy.

Context: Liver transplantation (LT) is considered the ideal therapy for patients with hepatocellular carcinoma (HCC) having cirrhosis but the shortage of liver donors and the risk of dropout from the wait list due to tumor progression severely limit transplantation. A new prognostic score, the HCC-model for end-stage liver disease (HCC-MELD), was developed by combining α-fetoprotein (AFP), MELD, and tumor size, to improve risk stratification of dropout in patients with HCC.

Objectives: In this study, we investigated the ability of the HCC-MELD score in predicting the posttransplant for patients fulfilling Milan criteria (MC).

Design: Two hundred patients with stage II tumor were retrospectively reviewed from a total of 1290 transplants performed at our institution from October 1997 through April 2015. Cox regression analysis was performed to identify the prognostic factors impacting the posttransplant survival.

Results: Overall survival at 1, 5, and 10 years was 89.3%, 71.1%, and 67.2%, whereas disease-free survival was 86.4%, 66.5%, and 52.4%, respectively. Multivariate analysis showed HCC-MELD score (hazard ratio [HR] 39.6, P < .001) and microvascular invasion (HR 2.41, P = .002) to be independent risk factors for recurrence, whereas HCC diameter (HR 1.15, P = .041), HCC-MELD (HR 15.611, P = .006), and grading (HR 2.17, P = .03) proved to be predictive factors of poor overall survival.

Conclusion: Our study showed the validity of the HCC-MELD equation in the evaluation of patients undergoing LT for HCC. This score offers a reliable method to assess the risk of waiting list dropout and predict posttransplantation outcomes.
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http://dx.doi.org/10.1177/1526924817746686DOI Listing
March 2018

Survival of children after liver transplantation for hepatocellular carcinoma.

Liver Transpl 2018 02;24(2):246-255

Research Group Epidemiological and Statistical Methods, Helmholtz Centre for Infection Research, Braunschweig, Germany.

Hepatocellular carcinoma (HCC) in childhood differs from adult HCC because it is often associated with inherited liver disease. It is, however, unclear whether liver transplantation (LT) for HCC in childhood with or without associated inherited disease has a comparable outcome to adult HCC. On the basis of data from the European Liver Transplant Registry (ELTR), we aimed to investigate if there are differences in patient and graft survival after LT for HCC between children and adults and between patients with underlying inherited versus noninherited liver disease, respectively. We included all 175 children who underwent LT for HCC and were enrolled in ELTR between 1985 and 2012. Of these, 38 had an associated inherited liver disease. Adult HCC patients with (n = 79) and without (n = 316, matched by age, sex, and LT date) inherited liver disease served as an adult comparison population. We used multivariable piecewise Cox regression models with shared frailty terms (for LT center) to compare patient and graft survival between the different HCC groups. Survival analyses demonstrated a superior longterm survival of children with inherited liver disease when compared with children with HCC without inherited liver disease (hazard ratio [HR], 0.29; 95% CI, 0.10-0.90; P = 0.03) and adults with HCC with inherited liver disease (HR, 0.27; 95% CI, 0.06-1.25; P = 0.09). There was no survival difference between adults with and without inherited disease (HR, 1.05; 95% CI, 0.66-1.66; P = 0.84). In conclusion, the potential survival advantage of children with an HCC based on inherited disease should be acknowledged when considering transplantation and prioritization for these patients. Further prospective studies accounting for tumor size and extension at LT are necessary to fully interpret our findings. Liver Transplantation 24 246-255 2018 AASLD.
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http://dx.doi.org/10.1002/lt.24994DOI Listing
February 2018
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