A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma in whom pathology registered pejorative histological markers (microvascular invasion and/or satellites; ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. From 1995 to 2012, 164 patients with hepatocellular carcinoma underwent resection. Eighty-five patients were potential candidates for liver transplantation and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed, and salvage liver transplantation was considered upon development of tumor recurrence/liver function impairment. Thirtyseven patients were at high risk and 48 at low risk of recurrence at pathology. Twenty-three out of 37 high-risk patients recurred during follow-up, but in nine of them the tumor burden extent contraindicated liver transplantation. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median posttransplant follow-up of 50.9 months, hepatocellular carcinoma had recurred in two patients and five patients had died, the 5-year survival being 82.4%. Twenty-six of the 48 low-risk patients developed recurrence, and 11 of them were transplanted. After a median posttransplant follow-up of 59 months, two patients developed recurrence and five died, their 5-year survival being 81.8%. Conclusion: Enlistment of patients at high risk of HCC recurrence after resection but before recurrence development seems a valid strategy and is associated with excellent long-term outcome; as early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment; however, once included on the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. (HEPATOLOGY 2016;63:839-849) H epatocellular carcinoma (HCC) is the most common primary tumor of the liver. The incidence of HCC is increasing in the United States and Europe, and it is currently the third leading cause of cancer-related death globally.(1,2) Liver transplantation (LT) is theoretically the treatment of choice because it allows removal not only of the tumor but also of the underlying cirrhosis. It offers a high survival rate and a low recurrence rate in well-selected cases. (3,4) Although Spain has the highest rate of
Background-Islet transplantation is a promising treatment for type 1 diabetes. Due to a shortage of suitable human pancreata, high cost, and the large dose of islets presently required for long-term diabetes reversal; it is important to maximize viable islet yield. Traditional methods of pancreas preservation have been identified as suboptimal due to insufficient oxygenation. Enhanced oxygen delivery is a key area of improvement. In this paper, we explored improved oxygen delivery by persufflation (PSF), ie, vascular gas perfusion.
Islet transplantation is emerging as a promising treatment for patients with type 1 diabetes. It is important to maximize viable islet yield for each organ due to scarcity of suitable human donor pancreata, high cost, and the high dose of islets required for insulin independence. However, organ transport for 8 hours using the two-layer method (TLM) frequently results in lower islet yields. Since efficient oxygenation of the core of larger organs (eg, pig, human) in TLM has recently come under question, we investigated oxygen persufflation as an alternative way to supply the pancreas with oxygen during preservation. Porcine pancreata were procured from non-heart-beating donors and preserved by either TLM or persufflation for 24 hours and fixed. Biopsies were collected from several regions of the pancreas, sectioned, stained with hematoxylin and eosin, and evaluated by a histologist. Persufflated tissues exhibited distended capillaries due to gas perfusion and significantly less autolysis/cell death than regions not exposed to persufflation or tissues exposed to TLM. The histology presented here suggests that after 24 hours of preservation, persufflation dramatically improves tissue health when compared with TLM. These results indicate the potential for persufflation to improve viable islet yields and extend the duration of preservation, allowing more donor organs to be utilized.ISLET TRANSPLANTATION is emerging as a promising treatment for patients with type I diabetes. 1,2 The minimally invasive nature of the procedure as well as the islets' intrinsic ability to tightly control blood glucose levels on demand via insulin release offer a combination of advantages that cannot be matched by other presently available treatments, such as selfmonitoring or whole-organ pancreas transplantation. Despite recent advances building upon the Edmonton Protocol 3 published in 2000, most centers still require multiple transplants to achieve long-term diabetes reversal. 4 The large dose of islets required, the high cost of the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A lack of proper oxygenation during preservation places hypoxic or anoxic stress on the tissue and may predispose islets to death during the isolation process.5 -8 It has been postulated that improving pancreas preservation via enhanced oxygenation may (1) extend the effective duration of preservation, (2) expand the donor pool up to 10-fold, (3) reduce the immunogenicity of transplanted islets, and (4) reduce the number of donors needed per patient. 9 Presently, the two-layer method (TLM) is the state of the ar...
Background-Current ex vivo quality assessment of donor kidneys is limited to vascular resistance measurements and histological analysis. New techniques for the assessment of organ quality before transplantation may further improve clinical outcomes while expanding the depleted deceased-donor pool. We propose the measurement of whole organ oxygen consumption rate (WOOCR) as a method to assess the quality of kidneys in real time before transplantation.
Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been suggested as a potential therapy for extensive bilobar liver tumors, although in some circumstances this technique may induce tumor progression, a fact still not well studied. Our aim was to study tumor hepatic progression induced by the first step of ALPPS in a WAG/Rij rat syngenic model of metastatic colorectal carcinoma by subcapsular CC531 cell line inoculation. ALPPS induced: tumor progression on deportalized lobe and metastases; expression of hepatic vasculogenic factors (HIF1-α and VEGF); and a dramatic increase of Kupffer cells (KCs) and tumor-associated macrophages (TAMs). Interestingly, KCs expressed COX-2 (M1 polarization), while TAMs expressed mainly arginase-1 (M2 polarization). ALPPS also induced a decrease of tumor-infiltrating lymphocytes and an increase of intrahepatic T lymphocytes. Thus, ALPPS technique seems to induce a hypoxic environment, which enhances hepatic HIF1-α and VEGF expression and may promote KCs and TAMs polarization. Consequently, the regenerative stimulus seems to be driven by a pro-inflammatory and hypoxic environment, in which M1 intrahepatic macrophages expressing COX-2 and T-Lymphocytes play a key role, facts which may be related with the tumor progression observed.
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