The Italian experience on liver transplantation for unresectable peri-hilar cholangiocarcinoma: a national survey and future perspectives.

Liver transplantation (LT) was considered an ineffective treatment for perihilar cholangiocarcinoma (pCCA) until the successful experience of the Mayo Clinic, proposing a protocol with strict inclusion criteria and neoadjuvant radio-chemotherapy. Since 2015, pCCA is considered an indication for LT in Italy only in the context of controlled prospective studies. We performed a survey among the 22 Italian Liver Transplant Centers to assess the results of LT for pCCA. Eight centers reported 53 cases from 1986 to 2021 (Bologna 12, Padova 10, Niguarda 10, Milano Tumori 8, Torino 5, Pisa 4, Ancona 2, Modena 2). Patients were divided according to whether they recieved neoadjuvant radio-chemotherapy (Group 1, 25 cases) or not (Group 2, 28 cases). Eleven patients were transplanted without neoadjuvant treatment after 2015. Overall survival at 1, 3 and 5 years was 83.8%, 56.6% and 50.6% in Group 1 and 72.4%, 41.4% and 35.5% in Gropu 2 (p = 0.13). Recurrence-free survival at 1, 3, and 5 years was 91.2%, 61.1% and 47.2% in Group 1 and 58.2%, 42.2%, and 36.1% in Group 2 (p = 0.16). A competing risk regression analysis showed a 5-year risk of cancer-related death of 19% for patients in Group 1 against 62.3% in Group 2, with a hazard ratio of 0.31 (95%CI [0.10-0.98], p 0.047). This survey promoted a discussion about the limitations of the Mayo protocol and set the basis for the adoption of a new nationwide protocol (LITHALICA-NCT06125769), having the same inclusion criteria but proposing standard of care chemotherapy as neoadjuvant regimen.

Perioperative thromboprophylaxis in liver transplant patients.

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation (LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications (intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors (portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ''rebalanced hemostasis'' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors (venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.

Long term results of hepatic resection or orthotopic liver transplantation in patients with liver metastases from gastrointestinal neuroendocrine tumors.

Hepatic metastases are one of the most important prognostic factors for survival among patients affected by gastrointestinal neuroendocrine tumors (NETs). The present study aims to evaluate the impact of surgery, including hepatic resection or orthotopic liver transplantation (OLT), on the outcome of patients affected by hepatic metastases from NETs, in terms of overall survival (OS). In this multicentric retrospective study, data was collected on 26 patients, who underwent surgery for hepatic metastases from NETs in two Italian University Clinics between January 1990 and December 2012; of which, 22 patients underwent hepatic resective surgery and 4 patients OLT. Hepatic metastases were synchronous in the 53.8% of cases and metachronous in the 46.2% of cases. The median number of resected hepatic metastases was 3. Surgical radicalness (R0) was reached in the 84.6% of cases. In total, 57.7% of patients had a recurrence, 66.7% of which were intra- and 33.3% extra-hepatic. The OS of patients that underwent hepatic resections and OLT was 44.9% [95% confidence interval (CI95), 26.0-77.7%] and 50% (CI95, 12.5-100.0%) at 5 years, respectively. Although the data regarding the survival of patients receiving surgery for hepatic metastases from NETs are encouraging, randomized clinical trials are necessary to more adequately evaluate the effect of surgery on survival of this group of patients.