Because of the organ shortage, non-heart-beating donors have been proposed as a possible source of grafts for orthotopic liver transplantation (OLT). Despite the widespread use of controlled non-heart-beating donors, there are only a few published studies reporting the outcomes with uncontrolled non-heart-beating donors (UNHBDs). A prospective case-control study on adult patients undergoing OLT was designed. We used normothermic extracorporeal membrane oxygenation (NECMO) in all UNHBDs. Matching 2:1 ratio comparison was performed between a study group (UNHBDs) and a brain death donor (BDD) control group. Between January 2006 and March 2008, a total of 60 patients were included: 20 in the UNHBD group and 40 in the control group. The incidence of ischemic cholangiopathy was 5% (n ϭ 1) for the UNHBD group and 0% for the BDD group (P ϭ 0.15). The rate of primary nonfunction was 10% (n ϭ 2) in UNHBD recipients and 2.5% (n ϭ 1) in BDD recipients (P ϭ 0.21), with graft loss in all of them. Three patients were retransplanted in the UNHBD group (15%), 2 of them because of primary nonfunction and 1 because of ischemic cholangiopathy; no patient was retransplanted in the control group (P ϭ 0.012). After a mean follow-up of 330.4 Ϯ 224.9 days, 1-year cumulative patient survival was 85.5% for the UNHBD group and 87.5% for the BDD group (P ϭ 0.768). One-year cumulative graft survival was 80% in the UNHBD group and 87.5% in the BDD group (P ϭ 0.774). In conclusion, UNHBDs under NECMO are a potential source of organs for OLT with encouraging outcomes potentially comparable to those obtained with BDDs.

Latest advances in the field of cancer immunotherapy have developed the (Chimeric Antigen Receptor) CAR-T cell therapy. This therapy was first used in hematological malignancies which obtained promising results; therefore, the use of CAR-T cells has become a popular approach for treating non-solid tumors. CAR-T cells consist of T-lymphocytes that are engineered to express an artificial receptor against any surface antigen of our choice giving us the capacity of offering precise and personalized treatment. This leaded to the development of CAR-T cells for treating solid tumors with the hope of obtaining the same result; however, their use in solid tumor and their efficacy have not achieved the expected results. The reason of these results is because solid tumors have some peculiarities that are not present in hematological malignancies. In this review we explain how CAR-T cells are made, their mechanism of action, adverse effect and how solid tumors can evade their action, and also we summarize their use in colorectal cancer and peritoneal carcinomatosis.

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Next-generation three-dimensional modelling software for personalized surgery allows spatially accurate depiction of the hepatic and vasculature anatomy based on the complexity and individual variation in each patient, and could facilitate decision-making about preoperative strategy in perihilar cholangiocarcinoma.

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Ovarian cancer is the seventh most common cancer worldwide in women and the most lethal gynecologic malignancy due to the lack of accurate screening tools for early detection and late symptom onset. The absence of early-onset symptoms often delays diagnosis until the disease has progressed to advanced stages, frequently when there is peritoneal involvement. Although ovarian cancer is a heterogeneous malignancy with different histopathologic types, treatment for advanced tumors is usually based on chemotherapy and cytoreduction surgery. CAR T cells have shown promise for the treatment of hematological malignancies, though their role in treating solid tumors remains unclear. Outcomes are less favorable owing to the low capacity of CAR T cells to migrate to the tumor site, the influence of the protective tumor microenvironment, and the heterogeneity of surface antigens on tumor cells. Despite these results, CAR T cells have been proposed as a treatment approach for peritoneal carcinomatosis from colorectal and gastric origin. Local intraperitoneal administration of CAR T cells has been found to be superior to systemic administration, as this route is associated with increased tumor reduction, a more durable effect, protection against local relapse and distant metastases, and fewer systemic adverse effects. In this article we review the application of CAR T cells for the treatment of ovarian cancer and peritoneal carcinomatosis from ovarian cancer.

Background: Peritoneal carcinomatosis from colorectal cancer is a highly challenging disease to treat, and as such constitutes a pressing issue in medicine. Adoptive transfer of chimeric antigen receptor-T (CAR-T) cells has shown impressive efficacy in hematologic malignancies, though the approach has been less effective in solid tumors when delivered via intravenous (i.v.) routes. We explored whether intraperitoneal administration of CAR-T cells could provide an effective and robust route for treatment of peritoneal carcinomatosis from colorectal cancer. Methods: To generate carcinoembryonic antigen (CEA)-specific CAR-T cells, we constructed a lentiviral transfer plasmid encoding a second-generation CAR composed of the single-chain variable fragment (scFv) from BW431/26, the CD8 alpha hinge region, 4-1BB co-stimulatory domain, and the CD3zeta T cell activation domain. We established various animal models of peritoneal carcinomatosis with intraperitoneal (i.p.) and extraperitoneal metastasis. Tumor-bearing animals were treated by i.p. or i.v. administration of CEA CAR-T cells. Treatment efficacy was evaluated and kinetic expansion and tissue distribution of CAR-T cells were studied. Results: CEA-directed CAR-T cells showed high tumor cell cytotoxicity in vitro. Intraperitoneally administered CAR-T cells exhibited superior antitumor activity compared to systemic i.v. cell infusion in an animal model of peritoneal carcinomatosis. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong antitumor activity in an animal model of peritoneal carcinomatosis with metastasis in intraperitoneal or extraperitoneal organs. Our data further indicate that when compared to systemic delivery, i.p. transfer of CAR-T cells could provide increased antitumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after intraperitoneal administration of our newly constructed prostate stem cell antigen (PSCA)-directed CAR-T cells. On a mechanistic level, our data evidenced rapid and high CAR-T cell expansion and high persistence in peripheral blood following i.p. cell administration. Conclusions: Intraperitoneal administration of CAR-T cells could be an effective and robust route for therapy of peritoneal carcinomatosis with metastasis in intra- and extraperitoneal organs. These findings hold great promise for CAR-T cell therapy in patients with peritoneal carcinomatosis.

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