Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Bile Duct Lithiasis Mimicking a Perihilar Cholangiocarcinoma-An Endless Dilemma: A Case Report.

Hilar bile duct strictures are mostly caused by malignant lesions. The morphological appearance of perihilar cholangiocarcinomas in various imaging modalities have other malignant and even benign mimics, which pose challenges to an accurate diagnosis and treatment and drive to futile surgery. Herein, we present the case of a 50-year-old woman admitted with jaundice and abdominal pain, elevated bilirubin level, liver function tests and carbohydrate antigen 19-9 level. Magnetic resonance cholangio-pancreatography (MR-CP) and the computed tomography with contrast enhancement revealed a suspected extrahepatic cholangiocarcinoma of the common bile duct. Further spontaneous resolution of the scenario, confirmed by diagnostic assessment, changed the clinical hypothesis in favor of a non-oncological disease. Indeed, the multidisciplinary evaluation supported a diagnosis of transient cholangitis secondary to non-evident intrahepatic lithiasis rather than cholangiocarcinoma. After a 26-month follow-up, the patient was asymptomatic with normal tumor markers and laboratory data. Consecutive MR-CPs showed no suspicion of malignancy. This case report underlines the need for an accurate preoperative assessment in patients with suspected cholangiocarcinoma.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

A narrative review of the current and future role of robotic surgery in liver surgery and transplantation.

Background: Minimally invasive surgery (MIS) is the technique of choice in selected patients for the treatment of liver tumors. The robotic approach is considered today the natural evolution of MIS. The application of the robotic technique in liver transplantation (LT) has been recently evaluated, especially in the living donation. The aim of this paper is to review the current role of the MIS and robotic donor hepatectomy in the literature and to evaluate the possible future implication in the transplant field. Methods: We conducted a narrative review using PubMed and Google Scholar for reports published so far, using the following keywords: minimally invasive liver surgery, laparoscopic liver surgery, robotic liver surgery, robotic living donation, laparoscopic donor hepatectomy and robotic donor hepatectomy. Results: Several advantages have been claimed in favor of robotic surgery: three-dimensional (3-D) imaging with stable and high-definition view; a more rapid learning curve than the laparoscopic one; the lack of hand tremors and the freedom of movements. Compared to open surgery, the benefits showed in the studies evaluating the robotic approach in the living donation are: less postoperative pain, the shorter period before returning to normal activity despite sustaining longer operation time. Furthermore, the 3-D and magnification view makes the technique excellent in distinguishing the right plane of transection, vascular and biliary anatomy, associated with high precision of the movements and a better bleeding control (essential for donor safety) and lower rate of vascular injury. Conclusions: The current literature does not fully support the superiority of the robotic approach versus laparoscopic or open method in living donor hepatectomy. Robotic donor hepatectomy performed by teams with high expertise and in properly selected living donors is safe and feasible. However, further data are necessary to evaluate properly the role of robotic surgery in the field of living donation.

The role of antiplatelet therapies on incidence and mortality of hepatocellular carcinoma.

AIM: To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment. METHODS: A systematic literature search was performed using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT. RESULTS: A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post-treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51-0.79; p < 0.001) as well as of post-treatment mortality (OR: 0.54; 95%CI = 0.35-0.83; p = 0.006). CONCLUSIONS: Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.

The current and future role of robotic surgery in liver surgery and transplantation.

Minimally invasive surgery (MIS) is gaining interest in all surgical fields, especially in the hepatobiliary and liver transplant branch with excellent outcomes. However, its application especially in the living donation, is at the beginning and still controversial, with few published studies. A literature review was performed using the following keywords reviewing the current role of robotic donor hepatectomy in the literature and to evaluate the possible future implication in the transplant field: minimally invasive liver surgery, laparoscopic liver surgery, robotic liver surgery, robotic living donation, laparoscopic donor hepatectomy, robotic donor hepatectomy. 3-D imaging with high definition and stable view, a more rapid learning curve than the laparoscopic one and the lack of hand tremors and the freedom of movements are all important advantages claimed in favor of robotic surgery. Furthermore, most of the studies showed, compared to open surgery, less postoperative pain, less intraoperative blood loss, and a shorter period before returning to normal activity to the detriment of longer operation time. The excellent outcome can be explained thanks to the three-dimensional and magnification view that allows for better evaluation compared to the laparoscopic approach to the right plane of transection, vascular and biliary anatomy, and thanks to the precision of the movements a better bleeding control. Robotic approach, especially in living donor hepatectomy, is considered safe and feasible, even if its superiority compared to the open and laparoscopic approaches needs further evaluation.

Early outcomes of kidney transplant recipients from donors with severe SARS-CoV-2 pneumonia: A report of 5 cases.

BACKGROUND: Transplanting kidneys from donors with a recent history of severe SARS-CoV-2 pneumonia is uncommon due to concerns about the risk of viral transmission and the quality of kidneys from these donors. To date, there are no conclusive data on viral transmission from extrapulmonary solid organ transplants. Given the prevalence of SARS-CoV-2 infections in potential donors, shortage of kidneys available for transplantation, and low risk of viral transmission, we developed a clinical protocol for accepting kidneys from donors with recent severe SARS-CoV-2 pneumonia who demonstrate preserved kidney function. MATERIALS AND METHODS: We collected data on early outcomes of 5 kidney transplant recipients from 4 deceased donors hospitalized for severe SARS-CoV-2 infection. RESULTS: Donor creatinine ranged from 0.51 to 0.60 mg/dL and kidney donor profile index (KDPI) from 14 to 52%. Three of the five kidneys were from donation after circulatory death. All recipients were fully vaccinated, and 4/5 received post-exposure prophylactic monoclonal antibody treatment. While 3 recipients had delayed graft function, all had excellent graft function at 3 or 4 weeks post-operatively. None of the recipients displayed signs or symptoms of SARS-CoV-2 infection post-transplant. CONCLUSION: Our findings suggest that kidney grafts from donors with a recent history of severe SARS-CoV-2 infection but with preserved kidney function can be safely used and have good early outcomes.

Pulsed Microwave Liver Ablation: An Additional Tool to Treat Hepatocellular Carcinoma.

This study aimed to analyze the outcomes of HCC patients treated with a novel technique-pulsed microwave ablation (MWA)-in terms of safety, local tumor progression (LTP), intrahepatic recurrence (IHR), and overall survival (OS). A total of 126 pulsed microwave procedures have been performed in our center. We included patients with mono- or multifocal HCC (BCLC 0 to D). The LTP at 12 months was 9.9%, with an IHR rate of 27.8% at one year. Survival was 92.0% at 12 months with 29.4% experiencing post-operative complications (28.6% Clavien-Dindo 1-2, 0.8% Clavien-Dindo 3-4). Stratifying patients by BCLC, we achieved BCLC 0, A, B, C, and D survival rates of 100%, 93.2%, 93.3%, 50%, and 100%, respectively, at one year, which was generally superior to or in line with the expected survival rates among patients who are started on standard treatment. The pulsed MWA technique is safe and effective. The technique can be proposed not only in patients with BCLC A staging but also in the highly selected cases of BCLC B, C, and D, confirming the importance of the concept of stage migration. This procedure, especially if performed with a minimally invasive technique (laparoscopic or percutaneous), is repeatable with a short postoperative hospital stay.

Colorectal Liver Metastases: A Literature Review of Viable Surgical Options with a Special Focus on Microwave Liver Thermal Ablation and Mini-Invasive Approach.

Colorectal cancer (CRC) is the third most common tumor worldwide and it is characterized in 20-30% of cases by liver involvement, which strongly affects the long-term patient outcome. There are many available therapies for liver colorectal metastases (CRLMs); the current standard of care is represented by liver resection, and when feasible, associated with systemic chemotherapy. Microwave thermal ablation (MWA) is a viable option in unresectable patients or to achieve treatment with a parenchymal spearing approach. A literature review was performed for studies published between January 2000 and July 2022 through a database search using PUBMED/Medline and the Cochrane Collaboration Library with the following MeSH search terms and keywords: microwave, ablation, liver metastases, colorectal neoplasm, and colon liver rectal metastases. The recurrence rate and overall patients' survival were evaluated, showing that laparoscopic MWA is safe and effective to treat CRLMs when resection is not feasible, or a major hepatectomy in fragile patients is necessary. Considering the low morbidity of this procedure, it is a viable option to treat patients with recurrent diseases in the era of effective chemotherapy and multimodal treatments.

Colon Rectal Liver Metastases: The Role of the Liver Transplantation in the Era of the Transplant Oncology and Precision Medicine.

The development of liver metastases in colon rectal cancer has a strong impact on the overall survival (OS) of the patient, with a 5-year survival rate of 5% with palliative treatment. Surgical resection combined with pharmacological treatment can achieve a 5-year OS rate of 31-58%. However, in only 20% of patients with colon rectal liver metastases (CRLMs), liver resection is feasible. In highly selected patients, recent trials and studies proved that liver transplantation (LT) for non-resectable CRLM is a surgical option with an excellent long-term OS. The paper aims to review the indications and outcome of LT for CRLMs, with a special focus on immunosuppressive therapy and the management of local and extrahepatic recurrence after LT.

Target Therapies for NASH/NAFLD: From the Molecular Aspect to the Pharmacological and Surgical Alternatives.

Non-alcoholic fatty liver disease represents an increasing cause of chronic hepatic disease in recent years. This condition usually arises in patients with multiple comorbidities, the so-called metabolic syndrome. The therapeutic options are multiple, ranging from lifestyle modifications, pharmacological options, to liver transplantation in selected cases. The choice of the most beneficial one and their interactions can be challenging. It is mandatory to stratify the patients according to the severity of their disease to tailor the available treatments. In our contribution, we review the most recent pharmacological target therapies, the role of bariatric surgery, and the impact of liver transplantation on the NAFLD outcome.

A Novel Entity Among Vascular Liver Tumors: The First Reported Liver Transplantation. Is It Feasible?

Liver transplant could be considered for certain tumors even if there is still dubious indication, as in the case of hepatic small vessels neoplasms that pose a difficult differential diagnosis with liver angiosarcoma. Liver transplant could be the best choice for patients with stable or slow-progressing tumors, for young patients with impaired quality of life, and when it would use organs that would be otherwise discarded but are capable of affording a good function. Vascular tumors are very heterogeneous cancers and our case represents the first description of a new histologic lesion that cannot be included in any of the pre-existing diagnostic categories. In our paper we want to present our decision to transplant a patient in whom the diagnosis was hepatic small vessels neoplasms (but was still in doubt for angiosarcoma as suggested by pathologists form other institutions). Furthermore, we want to highlight that after liver transplant, a new lesion never described before resulted from the specimen analysis that does not fit any of the pathologic diagnostic categories. This finding could open a scenario for additional improvement in molecular analysis in order to differentiate liver vascular tumors or even single lesion histotypes. This article emphasizes how little we know about the real behavior of liver vascular tumors and their clinical and therapeutic outcomes; we want to raise a question about the possibility for liver transplant in the setting of tumors not yet fully known and in which, in cases of diagnostic doubts, this option has been traditionally excluded, possibly bypassing ethical implications by using marginal donors.

Thoracoscopic Ablation of Critically Located Liver Tumors: A Safety and Efficacy Cohort Study.

Background: Liver resection represents the first curative treatment to treat primary and secondary hepatic tumors. Thoracoscopic liver ablation is a viable and minimally invasive alternative treatment, especially for patients with previous multiple abdominal surgeries. The aim of the study was to evaluate the safety and efficacy of thoracoscopic ablation for liver tumors. Methods: Retrospective analysis of a prospective database of patients with liver tumors, treated with thoracoscopic trans-diagrammatic ablation (MWA or RFA) at our institution from 2012 to 2018. The primary endpoint was post-operative mortality at 30 days, while secondary endpoints were morbidity and efficacy of ablation (i.e., response rate evaluated according to mRECIST criteria, and overall patient survival). Patient demographics, operational characteristics, and complications were recorded. Results: A total of 13 nodules were treated in 10 patients with a median age of 65.5 years. Post-operative mortality was 0%, and overall morbidity was 40% (Clavien-Dindo I complications 30%, II 0%, III 10%, IV 0%). Complete radiological response was obtained in 83.3% of nodules at 3 months. After a median follow-up of 20.95 months, the local tumor progression rate was 30%, with an intra-segmental-recurrence of 30%, and an intra-hepatic-recurrence of 30%. The overall 1-, 2-, and 3-years survival rates were 80%, 58%, and 58%. Conclusion: Thoracoscopic trans-diaphragmatic ablation proved to be a safe and effective way to treat liver tumors when abdominal approach is not feasible. Considering the low morbidity, it is a viable option to treat patients with recurrent disease and/or previous multiple abdominal surgeries.

Bile Microbiota in Liver Transplantation: Proof of Concept Using Gene Amplification in a Heterogeneous Clinical Scenario.

Objective: Historically, bile in the biliary tract has been considered sterile. Most of the series are based on patients with biliary tract diseases or the bile has been obtained with procedures susceptible to contamination. Methods: We evaluated the bile in a heterogeneous cohort of liver donors and recipient patients, with samples obtained in a sterile way, directly from the gallbladder and the common bile duct. Results: We assessed the bile microbiota in six liver donors and in six liver recipients after whole or split liver procedures in adult or pediatric recipients. Bile samples were studied using PCR sequencing of the 16S ribosomal RNA gene amplification (rDNA). Conclusions: We demonstrated that the bile is sterile, thereby ruling this out as a source of contamination following transplant.

Overview of Prognostic Systems for Hepatocellular Carcinoma and ITA.LI.CA External Validation of MESH and CNLC Classifications.

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described.