1,721,224 research outputs found
Refining selection criteria to further increase survival benefit in liver transplantation for unresectable colorectal liver metastases
Full text linkiver transplantation (LT) for hepatocellular carcinoma (HCC) was characterized in its early experience by high recurrence rates due to extensive tumor burden (1). Only after the adoption of Milan criteria (2), LT was recognized as a standard treatment for HCC (3). Besides HCC, other hepatic malignancies were proposed to be treated in the past with LT but due to the poor results observed (4), these indications were abandoned. Among them, colorectal liver metastases (CRLM) were considered an absolute contraindication until recently.
In June 2019, Dueland and colleagues published in Annals of Surgery a case series of 15 LT for unresectable CRLM with an estimated 5-year overall survival (OS) of 83% (5). This trial was named SECA-II and followed the previous SECA-I study (6). SECA-I was published 6 years before and showed a 5-year OS of 60% in 21 patients submitted to LT for unresectable CRLM. Four independent predictors of survival were identified, the so-called “Oslo criteria”: maximal tumor diameter <5.5 cm, time from primary cancer surgery >2 years, carcinoembryonic antigen (CEA) levels <80 μg/L and no progressive disease under chemotherapy. By applying these criteria in SECA-II, patients of the second trial had at the time of LT a significantly lower number of metastatic lesions (5 vs. 8), size of largest liver lesion (24 vs. 45 mm), preoperative CEA levels (2 vs. 15 μg/L) and longer time between primary tumor resection and LT (22.6 vs. 16.8 months) compared to SECA-I patients. However, if we look to table 2, radiological tumor features were significantly worse at diagnosis. The final tumor burden was the consequence of a partial response to neo-adjuvant therapies: patient in SECA-II trial had a 30% response according to RECIST criteria after chemotherapy or less (10–20%) in case of bridging treatments as transarterial chemoembolization or radioembolization. Response to chemotherapy in CRLM seems to be fundamental in selecting a more or less aggressive disease from the biological point of view, especially if a long waiting time before LT has to be expected. Similar is the prognostic value of the dynamic response to locoregional treatments, together with alpha-fetoprotein (AFP) and morphologic characteristics, to predict survival and recurrence in HCC patients (7). Such a refinement of selection criteria also in LT for CRLM turned into better OS as well as longer disease-free survival (DFS) in SECA-II: 1-year DFS increased from 35% to 53% with 4 patients (26.7%) having no recurrence 31 to 49 months after LT. Moreover, most of recurrences occurred in the lung (n=6) and were amenable of resection in almost all cases (5 out 6). Tumor growth was again controlled through the antiangiogenic activity of sirolimus (mTOR inhibitor) but, compared to SECA-I, it was introduced only after 4–6 weeks of tacrolimus, likely due to the occurrence of a high rate of hepatic artery thrombosis and rejection [reported in the literature to be associated with the administration of mTOR inhibitors (8)] in the first trial.
The good results showed by Dueland et al. can also be attributed to the low number of right-sided primary tumors (n=1) and KRAS mutations (n=1) included in the final study population, both of them already recognized as the two the most important prognostic factors for survival after liver resection (9,10). However, the impact of KRAS/BRAF mutation status on survival after LT is unknown, since mutational analysis was not performed at the time of SECA-I trial. On the other hand, a surrogate marker of tumor biology, the liver 18FDG-PET uptake rate, was lower in SECA-II compared to SECA-I. Only time of detection of hepatic metastases was reported to be more unfavourable in SECA-II (synchronous disease in 93% vs. 81% of cases).
The major challenge of LT for CRLM is represented by the shortage of organ donors which limits the wide application of this approach. New strategies are under investigation in the field of LT to expand the donor pool such as hypo/normothermic perfusion to restore borderline liver grafts or novel surgical techniques using auxiliary liver grafts, implanted either orthotopically or heterotopically (11,12). However, if allocation of organs for HCC patients should be based on the concept of transplant benefit (13), i.e., allocating the one available organ to the patient with the largest difference in posttransplant and waiting list lifetime, the survival gain obtained by LT is potentially greater in the setting of unresectable CRLM, given that the only alternative therapy for these patients is represented by palliative chemotherapy with 5-year OS of about 10% (14). Therefore, in theory, CRLM and HCC could equally compete each other given also that OS obtained by the Scandinavian group has been demonstrated to be similar or even higher than that one observed in HCC patients (11).
We do not know whether it is time to push the boundaries of liver transplant for unresectable CRLM but for sure, research should aim to refine selection criteria to further increase survival benefit of these patients who otherwise do not have any other chance of cure. Future studies, including prospective or randomized controlled multicenter trials, are awaited while others are already ongoing
Why is pancreatic adenocarcinoma not screened for earlier?
No full textWhy is pancreatic adenocarcinoma not screened for earlier
The multiple aspects of liver transplantation for hepatocellular carcinoma: comments on the recommendations from the consensus conference
No full textHepatocellular carcinoma (HCC) is a recognized indication for liver transplantation (LT) as it can at the same time provide a radical oncological resection and prevent its recurrence treating the hepatic disease. However the shortage of donors and the long time on waiting list forces the hepatologists and transplant surgeons to adopt bridging locoregional treatments to prevent the drop out and to perform downstaging treatments to offer a chance of radical intervention to more patients. The therapeutical strategies for patients suffering from HCC are various and different choices should be considered according to each patient's clinical situation according to prognostic and staging systems. Recently recommendations have been published on Lancet Oncology about this topic. These guidelines are very helpful in choosing among the different therapeutic options and in the management of patients in waiting list. Here we briefly summarize and comment the main features covered in the recommendations
99mTc-Mebrofenin Hepatobiliary Scintigraphy Combined With SPECT/CT to Assess Liver Function in Heterotopic Segmental Liver Transplantation in the Splenic Fossa
No full textABSTRACT: Recent studies have shown that the inclusion of a noninvasive and low-cost functional test such as hepatobiliary scintigraphy is considered more reliable than volume alone to predict posthepatectomy liver failure especially in light of new liver regeneration techniques. We herein reported the unique case of a 40-year-old man who underwent heterotopic liver transplantation of segments 2 and 3 in the splenic fossa after splenectomy for unresectable colorectal liver metastases. 99mTc-mebrofenin hepatobiliary scintigraphy combined with SPECT/CT was performed after liver transplantation to monitor graft function and regeneration before removal of the native liver
Reply to: "Impact of MELD 30-allocation policy on liver transplant outcomes in Italy: Considerations"
No full textNo abstrac
HYPOTHERMIC PERFUSION OF THE KIDNEY: FROM RESEARCH TO CLINICAL PRACTICE
No full textKidney transplantation is the treatment of choice for patients with end stage renal disease (ESRD). Donor availability is lower than demand, therefore suboptimal grafts retrieved from donors after brain death with expanded criteria donors (EC-DBD) and from donors after cardiac death (DCD) are in-creasingly used. These organs carry a higher risk of worse clinical outcomes, and subsequently need more advanced preservation systems than static cold storage (SCS). Hypothermic perfusion represents one of the aforementioned strategies.This review summarizes the main features of hypothermic perfusion: its mechanism of action through analysis of preclinical models and its clinical ef-ficacy in kidney transplantation with a focus on marginal donors. Oxygenated hypothermic perfusion was also evaluated focusing on its potential benefits on cell metabolism and graft immungenicity. Finally, as hypothermic perfu-sion not only allows to recover marginal grafts, but may also recondition grafts unsuitable for transplantation, the possible methods of graft evalu-ation and treatment options during perfusion are described in this review
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
