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1. The impact of postoperative complications on oncological outcomes of liver transplantation for hepatocellular carcinoma: A competing risk analysis

Author

Incarbone, N, De Carlis, R, Centonze, L, Bernasconi, D, Valsecchi, M, Lauterio, A, De Carlis, L, Incarbone N., De Carlis R., Centonze L., Bernasconi D. P., Valsecchi M. G., Lauterio A., De Carlis L., Incarbone, N, De Carlis, R, Centonze, L, Bernasconi, D, Valsecchi, M, Lauterio, A, De Carlis, L, Incarbone N., De Carlis R., Centonze L., Bernasconi D. P., Valsecchi M. G., Lauterio A., and De Carlis L.

Abstract

Objective: To investigate the influence of postoperative complications on tumor-related (TRD), disease-free survival (DFS) and overall survival (OS) in patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC). Methods: We retrospectively evaluated 425 LTs for HCC from 2010 to 2019. Postoperative complications were classified according to Comprehensive Complication Index (CCI) and the posttransplant risk of TRD assessed through Metroticket 2.0 calculator. The population was stratified into high-risk and low-risk cohorts based on the predicted TRD risk of 80%. In a second step, we re-evaluated TRD, DFS and OS of both cohorts according to a further stratification based on 47.3 points of CCI cut-off. Results: In the low-risk cohort, we observed a significantly better DFS (84% vs. 46%, p<0.001), TRD (3% vs. 26%, p<0.001) and OS (89% vs. 62%, p<0.001) in the group with CCI < 47.3. In the high-risk cohort, patients with CCI < 47.3 had significantly better DFS (50% vs. 23%, p = 0.003) and OS (68% vs. 42%, p = 0.02) and a comparable TRD (22% vs. 31%, p = 0.142). Conclusions: A complicated postoperative course negatively influenced long-term survival. This poorer oncological outcome associated with in-hospital postoperative complications suggests that every effort should be made to improve the early posttransplant course in HCC patients, including a careful donor-to recipient match and use of new perfusion technologies.

Published
2023

2. Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement

Author

Centonze, L, Gorga, G, De Carlis, R, Bernasconi, D, Lauterio, A, Carbonaro, L, Vella, I, Sgrazzutti, C, Incarbone, N, Rizzetto, F, Valsecchi, M, Vanzulli, A, De Carlis, L, Centonze, Leonardo, Gorga, Giovanna, De Carlis, Riccardo, Bernasconi, Davide, Lauterio, Andrea, Carbonaro, Luca, Vella, Ivan, Sgrazzutti, Cristiano, Incarbone, Niccolò, Rizzetto, Francesco, Valsecchi, Maria Grazia, Vanzulli, Angelo, De Carlis, Luciano, Centonze, L, Gorga, G, De Carlis, R, Bernasconi, D, Lauterio, A, Carbonaro, L, Vella, I, Sgrazzutti, C, Incarbone, N, Rizzetto, F, Valsecchi, M, Vanzulli, A, De Carlis, L, Centonze, Leonardo, Gorga, Giovanna, De Carlis, Riccardo, Bernasconi, Davide, Lauterio, Andrea, Carbonaro, Luca, Vella, Ivan, Sgrazzutti, Cristiano, Incarbone, Niccolò, Rizzetto, Francesco, Valsecchi, Maria Grazia, Vanzulli, Angelo, and De Carlis, Luciano

Abstract

Background. The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT. Methods. Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis. Results. A TSA exceeding 78.54 mm2resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018). Conclusions. Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts.

Published
2023

3. A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation : every nodule matters

Author

Centonze, L, Di Sandro, S, Lauterio, A, De Carlis, R, Sgrazzutti, C, Ciulli, C, Vella, I, Vicentin, I, Incarbone, N, Bagnardi, V, Vanzulli, A, De Carlis, L, Centonze L., Di Sandro S., Lauterio A., De Carlis R., Sgrazzutti C., Ciulli C., Vella I., Vicentin I., Incarbone N., Bagnardi V., Vanzulli A., De Carlis L., Centonze, L, Di Sandro, S, Lauterio, A, De Carlis, R, Sgrazzutti, C, Ciulli, C, Vella, I, Vicentin, I, Incarbone, N, Bagnardi, V, Vanzulli, A, De Carlis, L, Centonze L., Di Sandro S., Lauterio A., De Carlis R., Sgrazzutti C., Ciulli C., Vella I., Vicentin I., Incarbone N., Bagnardi V., Vanzulli A., and De Carlis L.

Abstract

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64–0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48–0.72] when LI-RADS-5 and LI-RADS-TR-V (P = 0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P = 0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54–0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P = 0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to

Published
2021

4. Discovery of a Rare Variant of the Arc of Bühler During Liver Procurement

Author

Incarbone, N, De Carlis, R, Centonze, L, Lauterio, A, De Carlis, L, Incarbone N., De Carlis R., Centonze L., Lauterio A., De Carlis L., Incarbone, N, De Carlis, R, Centonze, L, Lauterio, A, De Carlis, L, Incarbone N., De Carlis R., Centonze L., Lauterio A., and De Carlis L.

Abstract

We report a rare variant of the hepatic arterial supply observed during liver procurement from a 71-year-old female donor for whom an ischemic stroke caused brain death. Preoperative computed tomography showed a partially obliterated celiac trunk and an atypical arterial branch that coursed in a retropancreatic plane away from its origin at the superior mesenteric artery to anastomose with the common hepatic artery at the origin of the proper hepatic artery. The gastroduodenal artery and the dorsal pancreatic artery are the 2 conventional anastomotic arcades between the celiac trunk and the superior mesenteric artery. However, another potential anastomotic route is a rare physiological phenomenon known as the arc of Bühler, which, if present, connects the superior mesenteric artery with the celiac trunk or one of its branches. Although the arc of Bühler is known to occur in less than 3% of the general population, it could serve as a crucial anastomotic option in the case of median arcuate ligament syndrome or atheromatous obliteration of the celiac trunk. In our case, we were able to dissect and preserve the entire anastomotic arc from the donor. For arterial reconstruction during liver transplant, we anastomosed the arc of Bühler to the recipient’s hepatic artery at the origin of the gastroduodenal artery. The postoperative course was uneventful, and the recipient was in good health at the 6-month follow-up. The arc of Bühler, when present, is an important anastomotic option in hepatobiliary surgery to avoid potential damage to the arterial supply of the liver.

Published
2021

5. Impact of the COVID-19 pandemic on liver donation and transplantation: A review of the literature

Author

de Carlis, R, Vella, I, Incarbone, N, Centonze, L, Buscemi, V, Lauterio, A, de Carlis, L, de Carlis R., Vella I., Incarbone N., Centonze L., Buscemi V., Lauterio A., de Carlis L., de Carlis, R, Vella, I, Incarbone, N, Centonze, L, Buscemi, V, Lauterio, A, de Carlis, L, de Carlis R., Vella I., Incarbone N., Centonze L., Buscemi V., Lauterio A., and de Carlis L.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation (LT) activity. During the first pandemic wave, administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a lifesaving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients. Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients, design COVID-safe clinical pathways, and promote telehealth to prevent nosocomial transmission. Despite the ever-growing literature on COVID-19, the amount of high-quality literature on LT remains limited. This review will provide an updated view of the impact of the pandemic on LT programs worldwide. Donor and recipient screening, strategies for waitlist prioritization, and posttransplant risk of infection and mortality are discussed. Moreover, a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients.

Published
2021

7. Current surgical management of peri-hilar and intra-hepatic cholangiocarcinoma

Author

Lauterio, A, De Carlis, R, Centonze, L, Buscemi, V, Incarbone, N, Vella, I, De Carlis, L, Lauterio A., De Carlis R., Centonze L., Buscemi V., Incarbone N., Vella I., De Carlis L., Lauterio, A, De Carlis, R, Centonze, L, Buscemi, V, Incarbone, N, Vella, I, De Carlis, L, Lauterio A., De Carlis R., Centonze L., Buscemi V., Incarbone N., Vella I., and De Carlis L.

Abstract

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, preoperative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Published
2021

8. Incarcerated sigmoid large-cell neuroendocrine carcinoma in an inguinal hernia

Author

Gerosa, M, Incarbone, N, Di Fratta, E, Mari, G, Guttadauro, A, Cioffi, U, Maggioni, D, Mari, GM, Gerosa, M, Incarbone, N, Di Fratta, E, Mari, G, Guttadauro, A, Cioffi, U, Maggioni, D, and Mari, GM

Abstract

Large-cell neuroendocrine carcinomas (NECs) of the colon are extremely rare aggressive tumors. A 79-year-old man presented at our hospital for muco-hematic diarrhea, weight loss and incarcerated hernia in his left groin. Colonoscopy revealed sigmoid stenosis. Computed tomography confirmed an incarcerated hernia containing sigmoid mass and massive abdominal adenopathy. In absence of colonic obstruction, the patient underwent elective palliative sigmoid resection and colostomy by laparoscopic approach, and direct hernia repair through inguinal access. Histopathological examination revealed a large cells sigmoid NEC. We report the first case of large-cell neuroendocrine colon cancer incarcerated in an inguinal hernia. Due to the advanced stage, we have performed a palliative laparoscopic resection in order to reduce surgical trauma, confirm pre-operative results and minimize post-operative complications, and direct hernia repair through inguinal access.

Published
2021

9. Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement

Author

Leonardo Centonze, Giovanna Gorga, Riccardo De Carlis, Davide Bernasconi, Andrea Lauterio, Luca Carbonaro, Ivan Vella, Cristiano Sgrazzutti, Niccolò Incarbone, Francesco Rizzetto, Maria Grazia Valsecchi, Angelo Vanzulli, Luciano De Carlis, Centonze, L, Gorga, G, De Carlis, R, Bernasconi, D, Lauterio, A, Carbonaro, L, Vella, I, Sgrazzutti, C, Incarbone, N, Rizzetto, F, Valsecchi, M, Vanzulli, A, and De Carlis, L

Subjects
Transplantation, liver transpant, spontaneous portosystemic shunts
Abstract

Background. The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT. Methods. Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis. Results. A TSA exceeding 78.54 mm2resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018). Conclusions. Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts.

Published
2023
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10. A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation: every nodule matters

Author

Cristina Ciulli, Leonardo Centonze, Ivan Vella, Stefano Di Sandro, Ilaria Vicentin, Andrea Lauterio, Cristiano Sgrazzutti, Niccolò Incarbone, Luciano De Carlis, Riccardo De Carlis, Angelo Vanzulli, Vincenzo Bagnardi, Centonze, L, Di Sandro, S, Lauterio, A, De Carlis, R, Sgrazzutti, C, Ciulli, C, Vella, I, Vicentin, I, Incarbone, N, Bagnardi, V, Vanzulli, A, and De Carlis, L

Subjects
medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Contrast Media, Liver transplantation, Sensitivity and Specificity, liver imaging, law.invention, law, medicine, hepatocellular carcinoma, LI-RADS, liver transplantation, Metroticket 2.0, tumour staging, Humans, Liver imaging, Retrospective Studies, Transplantation, business.industry, Liver Neoplasms, Nodule (medicine), Retrospective cohort study, medicine.disease, Magnetic Resonance Imaging, Confidence interval, Liver Transplantation, Single centre, Calculator, Hepatocellular carcinoma, Radiology, medicine.symptom, business, Tomography, X-Ray Computed
Abstract

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64–0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48–0.72] when LI-RADS-5 and LI-RADS-TR-V (P=0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P=0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54–0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P=0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance.

Published
2021

11. Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma

Author

Andrea Lauterio, Luciano De Carlis, Vincenzo Buscemi, Riccardo De Carlis, Niccolò Incarbone, Ivan Vella, Leonardo Centonze, Lauterio, A, De Carlis, R, Centonze, L, Buscemi, V, Incarbone, N, Vella, I, and De Carlis, L

Subjects
Cancer Research, medicine.medical_specialty, extended liver resection, medicine.medical_treatment, Tumor resection, Peri, Hilum (biology), Portal vein ligation, Review, 030230 surgery, Liver transplantation, 03 medical and health sciences, 0302 clinical medicine, medicine, MED/18 - CHIRURGIA GENERALE, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), intra-hepatic cholangiocarcinoma (i-CCA), Radioembolization, Intrahepatic Cholangiocarcinoma, RC254-282, business.industry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Biliary cancer, Neoadjuvant chemoradiation, peri-hilar cholangiocarcinoma (h-CCA), Trans-arterial chemoembolization (TACE), Oncology, 030220 oncology & carcinogenesis, Peri-hilar cholangiocarci-noma (h-CCA), cardiovascular system, portal vein embolization (PVE), Radiology, Hepatectomy, business, cholangiocarcinoma
Abstract

Simple Summary The treatment of peri-hilar (h-CCA) and intrahepatic (i-CCA) cholangiocarcinoma is an evolving field in hepato-pancreato-biliary surgery. Continuous development of radiological and surgical techniques currently offers different treatment strategies, ranging from traditional hepatectomies to complex approaches involving preoperative portal vein embolization or associating liver partition and portal vein ligation for staged hepatectomy. Recent advances in perioperative chemo-radiotherapy have improved patient survival and have been incorporated into transplant protocols, yielding excellent results. We report a comprehensive review of current surgical and multimodal approaches to h-CCA and i-CCA treatment. Abstract Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Published
2021

12. Machine Perfusion for Kidneys With Multiple Arteries: An Unusual Reconstruction With an Iliac Arterial Graft

Author

Riccardo De Carlis, Iacopo Mangoni, Niccolò Incarbone, Luciano De Carlis, Andrea Lauterio, De Carlis, R, Mangoni, I, Lauterio, A, Incarbone, N, and De Carlis, L

Subjects
Transplantation, Machine perfusion, business.industry, Organ preservation, Arteries, Back-table preparation, Kidney, Iliac Artery, Perfusion, Kidney transplantation, Treatment Outcome, Humans, Medicine, business, Nuclear medicine
Published
2021
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13. Impact of the COVID-19 pandemic on liver donation and transplantation: A review of the literature

Author

Ivan Vella, Riccardo De Carlis, Luciano De Carlis, Andrea Lauterio, Vincenzo Buscemi, Niccolò Incarbone, Leonardo Centonze, de Carlis, R, Vella, I, Incarbone, N, Centonze, L, Buscemi, V, Lauterio, A, and de Carlis, L

Subjects
medicine.medical_specialty, Tissue and Organ Procurement, medicine.medical_treatment, Graft vs Host Disease, Transplants, Telehealth, Liver transplantation, Liver cirrhosi, Health care rationing, 03 medical and health sciences, Donor and recipient screening, 0302 clinical medicine, Donor-to-recipient transmission, Pandemic, Disease Transmission, Infectious, Medicine, Humans, Mass Screening, Intensive care medicine, Mass screening, Health Care Rationing, business.industry, SARS-CoV-2, Resource allocation in transplantation, Risk of infection, Gastroenterology, COVID-19, Minireviews, General Medicine, Severe acute respiratory syndrome coronavirus type 2, Liver Transplantation, Transplantation, 030220 oncology & carcinogenesis, Donation, Liver cirrhosis, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, Immunosuppression
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation (LT) activity. During the first pandemic wave, administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a life-saving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients. Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients, design COVID-safe clinical pathways, and promote telehealth to prevent nosocomial transmission. Despite the ever-growing literature on COVID-19, the amount of high-quality literature on LT remains limited. This review will provide an updated view of the impact of the pandemic on LT programs worldwide. Donor and recipient screening, strategies for waitlist prioritization, and posttransplant risk of infection and mortality are discussed. Moreover, a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients.

Published
2021

14. The impact of postoperative complications on oncological outcomes of liver transplantation for hepatocellular carcinoma: A competing risk analysis.

Author

Incarbone N, De Carlis R, Centonze L, Bernasconi DP, Valsecchi MG, Lauterio A, and De Carlis L

Subjects
Humans, Retrospective Studies, Risk Assessment, Postoperative Complications epidemiology, Postoperative Complications etiology, Neoplasm Recurrence, Local epidemiology, Carcinoma, Hepatocellular pathology, Liver Transplantation adverse effects, Liver Neoplasms pathology
Abstract

Objective: To investigate the influence of postoperative complications on tumor-related (TRD), disease-free survival (DFS) and overall survival (OS) in patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC)., Methods: We retrospectively evaluated 425 LTs for HCC from 2010 to 2019. Postoperative complications were classified according to Comprehensive Complication Index (CCI) and the posttransplant risk of TRD assessed through Metroticket 2.0 calculator. The population was stratified into high-risk and low-risk cohorts based on the predicted TRD risk of 80%. In a second step, we re-evaluated TRD, DFS and OS of both cohorts according to a further stratification based on 47.3 points of CCI cut-off., Results: In the low-risk cohort, we observed a significantly better DFS (84% vs. 46%, p<0.001), TRD (3% vs. 26%, p<0.001) and OS (89% vs. 62%, p<0.001) in the group with CCI < 47.3. In the high-risk cohort, patients with CCI < 47.3 had significantly better DFS (50% vs. 23%, p = 0.003) and OS (68% vs. 42%, p = 0.02) and a comparable TRD (22% vs. 31%, p = 0.142)., Conclusions: A complicated postoperative course negatively influenced long-term survival. This poorer oncological outcome associated with in-hospital postoperative complications suggests that every effort should be made to improve the early posttransplant course in HCC patients, including a careful donor-to recipient match and use of new perfusion technologies., Competing Interests: Conflict of Interest We have no conflicts of interest to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Published
2023
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15. Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement.

Author

Centonze L, Gorga G, De Carlis R, Bernasconi D, Lauterio A, Carbonaro L, Vella I, Sgrazzutti C, Incarbone N, Rizzetto F, Valsecchi MG, Vanzulli A, and De Carlis L

Subjects
Humans, Retrospective Studies, Graft Survival, Risk Factors, Liver Cirrhosis, Liver Transplantation adverse effects, Portasystemic Shunt, Transjugular Intrahepatic adverse effects, Acute Kidney Injury etiology
Abstract

Background: The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT., Methods: Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis., Results: A TSA exceeding 78.54 mm 2 resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018)., Conclusions: Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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17. From LI-RADS Classification to HCC Pathology: A Retrospective Single-Institution Analysis of Clinico-Pathological Features Affecting Oncological Outcomes after Curative Surgery.

Author

Centonze L, De Carlis R, Vella I, Carbonaro L, Incarbone N, Palmieri L, Sgrazzutti C, Ficarelli A, Valsecchi MG, Dello Iacono U, Lauterio A, Bernasconi D, Vanzulli A, and De Carlis L

Abstract

Background : The latest Liver Imaging Reporting and Data System (LI-RADS) classification by the American College of Radiology has been recently endorsed in the American Association for the Study of Liver Disease (AASLD) guidelines for Hepatocellular carcinoma (HCC) management. Although the LI-RADS protocol has been developed as a diagnostic algorithm, there is some evidence concerning a possible correlation between different LI-RADS classes and specific pathological features of HCC. We aimed to investigate such radiological/pathological correlation and the possible prognostic implication of LI-RADS on a retrospective cohort of HCC patients undergoing surgical resection. Methods : We performed a retrospective analysis of the pathological characteristics of resected HCC, exploring their distribution among different LI-RADS classes and analyzing the risk factors for recurrence-free, overall and cancer-specific survival Results : LI-RADS-5 (LR-5) nodules showed a higher prevalence of microvascular invasion (MVI), satellitosis and capsule infiltration, as well as higher median values of alpha-fetoprotein (αFP) compared to LI-RADS-3/4 (LR-3/4) nodules. MVI, αFP, satellitosis and margin-positive (R1) resection resulted as independent risk factors for recurrence-free survival, while LI-RADS class did not exert any significant impact. Focusing on overall survival, we identified patient age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Model for End Stage Liver Disease (MELD) score, αFP, MVI, satellitosis and R1 resection as independent risk factors for survival, without any impact of LI-RADS classification. Last, MELD score, log10αFP, satellitosis and R1 resection resulted as independent risk factors for cancer-specific survival, while LI-RADS class did not exert any significant impact. Conclusions : Our results suggest an association of LR-5 class with unfavorable pathological characteristics of resected HCC; tumor histology and underlying patient characteristics such as age, ECOG-PS and liver disease severity exert a significant impact on postoperative oncological outcomes.

Published
2022
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18. Discovery of a Rare Variant of the Arc of Bühler During Liver Procurement.

Author

Incarbone N, De Carlis R, Centonze L, Lauterio A, and De Carlis L

Subjects
Aged, Female, Hepatic Artery diagnostic imaging, Hepatic Artery surgery, Humans, Liver, Treatment Outcome, Celiac Artery diagnostic imaging, Celiac Artery surgery, Mesenteric Artery, Superior
Abstract

We report a rare variant of the hepatic arterial supply observed during liver procurement from a 71-year-old female donor for whom an ischemic stroke caused brain death. Preoperative computed tomography showed a partially obliterated celiac trunk and an atypical arterial branch that coursed in a retropancreatic plane away from its origin at the superior mesenteric artery to anastomose with the common hepatic artery at the origin of the proper hepatic artery. The gastroduodenal artery and the dorsal pancreatic artery are the 2 conventional anastomotic arcades between the celiac trunk and the superior mesenteric artery. However, another potential anastomotic route is a rare physiological phenomenon known as the arc of Bühler, which, if present, connects the superior mesenteric artery with the celiac trunk or one of its branches. Although the arc of Bühler is known to occur in less than 3% of the general population, it could serve as a crucial anastomotic option in the case of median arcuate ligament syndrome or atheromatous obliteration of the celiac trunk. In our case, we were able to dissect and preserve the entire anastomotic arc from the donor. For arterial reconstruction during liver transplant, we anastomosed the arc of Bühler to the recipient's hepatic artery at the origin of the gastroduodenal artery. The postoperative course was uneventful, and the recipient was in good health at the 6-month follow-up. The arc of Bühler, when present, is an important anastomotic option in hepatobiliary surgery to avoid potential damage to the arterial supply of the liver.

Published
2021
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19. A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation: every nodule matters.

Author

Centonze L, Di Sandro S, Lauterio A, De Carlis R, Sgrazzutti C, Ciulli C, Vella I, Vicentin I, Incarbone N, Bagnardi V, Vanzulli A, and De Carlis L

Subjects
Contrast Media, Humans, Magnetic Resonance Imaging, Retrospective Studies, Sensitivity and Specificity, Tomography, X-Ray Computed, Carcinoma, Hepatocellular diagnostic imaging, Carcinoma, Hepatocellular surgery, Liver Neoplasms diagnostic imaging, Liver Neoplasms surgery, Liver Transplantation
Abstract

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64-0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48-0.72] when LI-RADS-5 and LI-RADS-TR-V (P = 0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P = 0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54-0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P = 0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Published
2021
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21. Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma.

Author

Lauterio A, De Carlis R, Centonze L, Buscemi V, Incarbone N, Vella I, and De Carlis L

Abstract

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

Published
2021
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22. Impact of the COVID-19 pandemic on liver donation and transplantation: A review of the literature.

Author

De Carlis R, Vella I, Incarbone N, Centonze L, Buscemi V, Lauterio A, and De Carlis L

Subjects
COVID-19 diagnosis, COVID-19 transmission, Disease Transmission, Infectious prevention & control, Graft vs Host Disease prevention & control, Health Care Rationing, Humans, Immunosuppressive Agents therapeutic use, Mass Screening, SARS-CoV-2, Transplants virology, COVID-19 epidemiology, Liver Transplantation trends, Tissue and Organ Procurement trends
Abstract

The coronavirus disease 2019 (COVID-19) pandemic has upended healthcare systems worldwide and led to an inevitable decrease in liver transplantation (LT) activity. During the first pandemic wave, administrators and clinicians were obliged to make the difficult decision of whether to suspend or continue a life-saving procedure based on the scarce available evidence regarding the risk of transmission and mortality in immunosuppressed patients. Those centers where the activity continued or was heavily restricted were obliged to screen donors and recipients, design COVID-safe clinical pathways, and promote telehealth to prevent nosocomial transmission. Despite the ever-growing literature on COVID-19, the amount of high-quality literature on LT remains limited. This review will provide an updated view of the impact of the pandemic on LT programs worldwide. Donor and recipient screening, strategies for waitlist prioritization, and posttransplant risk of infection and mortality are discussed. Moreover, a particular focus is given to the possibility of donor-to-recipient transmission and immunosuppression management in COVID-positive recipients., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests for this article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2021
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23. Incarcerated sigmoid large-cell neuroendocrine carcinoma in an inguinal hernia.

Author

Gerosa M, Incarbone N, Di Fratta E, Mari GM, Guttadauro A, Cioffi U, and Maggioni D

Abstract

Large-cell neuroendocrine carcinomas (NECs) of the colon are extremely rare aggressive tumors. A 79-year-old man presented at our hospital for muco-hematic diarrhea, weight loss and incarcerated hernia in his left groin. Colonoscopy revealed sigmoid stenosis. Computed tomography confirmed an incarcerated hernia containing sigmoid mass and massive abdominal adenopathy. In absence of colonic obstruction, the patient underwent elective palliative sigmoid resection and colostomy by laparoscopic approach, and direct hernia repair through inguinal access. Histopathological examination revealed a large cells sigmoid NEC. We report the first case of large-cell neuroendocrine colon cancer incarcerated in an inguinal hernia. Due to the advanced stage, we have performed a palliative laparoscopic resection in order to reduce surgical trauma, confirm pre-operative results and minimize post-operative complications, and direct hernia repair through inguinal access., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2021.)

Published
2021
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