Pablo Martí

Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma

BACKGROUND Occasionally, patients with hepatocellular carcinoma (HCC) who receive radioembolization with palliative intent are downstaged for radical treatments. The aim of this study was to describe and analyze the overall survival (OS) in these patients compared with patients of the same baseline stage (UNOS T3), who were not eligible for radical treatment after radioembolization. METHODS Between September 2003 and August 2010, 118 patients with HCC received radioembolization with yttrium-90 ((90)Y) resin microspheres. Of these, 21 patients with UNOS T3 stage were retrospectively identified and included in this analysis. RESULTS In total, 6 of 21 patients were downstaged and treated radically between 2 and 35 months post-radioembolization. Three patients were resected, 2 received liver transplantation and 1 was ablated and then resected. Patients treated radically were significantly younger (62 vs. 73 years, p = 0.006) and had higher tumor volume (583 mL vs. 137 mL, p = 0.001) than patients who did not achieve radical treatment. There were no differences between the groups in number of lesions, BCLC stage, previous cirrhosis, activity administered per tumor volume, or median levels of alpha-fetoprotein or total bilirubin. Across the whole series, the median OS was 27.0 months (95% CI 5.0-48.9), varying significantly between those treated radically (OS not reached after a median follow-up of 41.5 months since radical therapy) and those who received palliative treatment only (22.0 months; 95% CI 15.0-30.9). CONCLUSIONS Radical therapy following tumor downstaging with radioembolization provides the possibility of long-term survival in a select subgroup (UNOS T3 stage) with otherwise limited options.

Risk factors of lung, head and neck, esophageal, and kidney and urinary tract carcinomas after liver transplantation: the effect of smoking withdrawal.

Liver transplant recipients have an increased risk of malignancy. Smoking is related to some of the most frequent causes of posttransplant malignancy. The incidence and risk factors for the development of neoplasia related to smoking (head and neck, lung, esophageal, and kidney and urinary tract carcinomas) were studied in 339 liver transplant recipients. Risk factors for the development of smoking‐related neoplasia were also studied in 135 patients who had a history of smoking so that it could be determined whether smoking withdrawal was associated with a lower risk of malignancy. After a mean follow‐up of 7.5 years, 26 patients were diagnosed with 29 smoking‐related malignancies. The 5‐ and 10‐year actuarial rates were 5% and 13%, respectively. In multivariate analysis, smoking and older age were independently associated with a higher risk of malignancy. In the smoker subgroup, the variables related to a higher risk of malignancy were active smoking and older age. In conclusion, smoking withdrawal after liver transplantation may have a protective effect against the development of neoplasia. Liver Transpl, 2011.

Activation of Noncanonical Wnt Signaling Through WNT5A in Visceral Adipose Tissue of Obese Subjects Is Related to Inflammation

CONTEXT Wingless-type mouse mammary tumor virus integration site family (WNT)-5A is a glycoprotein involved in the regulation of the inflammatory response by activating the noncanonical Wnt signaling pathway. Secreted frizzled-related protein (SFRP)-5 acts as a decoy receptor that binds and sequesters WNT5A, preventing activation of frizzled receptors and attenuating the noncanonical Wnt signaling. OBJECTIVE The aim of the study was to evaluate the involvement of WNT5A and SFRP5 in obesity and obesity-related comorbidities as well as to explore their effect in visceral adipose tissue inflammation. PATIENTS AND METHODS Samples obtained from 90 subjects were used. Circulating and gene expression levels of WNT5A and SFRP5 were analyzed in different metabolic tissues. The effect of TNF-α and lipopolysaccharide on the transcript levels of WNT5A and SFRP5 in adipocytes was explored. We also investigated whether WNT5A itself can activate an inflammatory response. RESULTS Increased circulating levels of WNT5A in obese patients (P < .05) were decreased (P < .001) after gastric bypass. In this line, WNT5A mRNA in visceral adipose tissue was increased (P < .05) in obese patients with gene expression levels of SFRP5 being down-regulated (P < .05). WNT5A mRNA expression was significantly enhanced (P < .01) by lipopolysaccharide and TNF-α treatment, whereas no effects were found in SFRP5 gene expression levels. Furthermore, exogenous WNT5A induced (P < .05) IL-6, IL1B, MMP2, MMP9, and SSP1 mRNA expression in human adipocyte cultures. CONCLUSIONS Activation of noncanonical Wnt signaling through the up-regulation of WNT5A and down-regulation of SFRP5 may promote a proinflammatory state in visceral adipose tissue contributing to the development of obesity-associated comorbidities.

Increased Obesity-Associated Circulating Levels of the Extracellular Matrix Proteins Osteopontin, Chitinase-3 Like-1 and Tenascin C Are Associated with Colon Cancer.

Background Excess adipose tissue represents a major risk factor for the development of colon cancer with inflammation and extracellular matrix (ECM) remodeling being proposed as plausible mechanisms. The aim of this study was to investigate whether obesity can influence circulating levels of inflammation-related extracellular matrix proteins in patients with colon cancer (CC), promoting a microenvironment favorable for tumor growth. Methods Serum samples obtained from 79 subjects [26 lean (LN) and 53 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (44 without CC and 35 with CC). Anthropometric measurements as well as circulating metabolites and hormones were determined. Circulating concentrations of the ECM proteins osteopontin (OPN), chitinase-3-like protein 1 (YKL-40), tenascin C (TNC) and lipocalin-2 (LCN-2) were determined by ELISA. Results Significant differences in circulating OPN, YKL-40 and TNC concentrations between the experimental groups were observed, being significantly increased due to obesity (P<0.01) and colon cancer (P<0.05). LCN-2 levels were affected by obesity (P<0.05), but no differences were detected regarding the presence or not of CC. A positive association (P<0.05) with different inflammatory markers was also detected. Conclusions To our knowledge, we herein show for the first time that obese patients with CC exhibit increased circulating levels of OPN, YKL-40 and TNC providing further evidence for the influence of obesity on CC development via ECM proteins, representing promising diagnostic biomarkers or target molecules for therapeutics.

Portal Revascularization in the Setting of Cavernous Transformation Through a Paracholedocal Vein: A Case Report

Diffuse thrombosis of the entire portal system (PVT) and cavernomatous transformation of the portal vein (CTPV) represents a demanding challenge in liver transplantation. We present the case of a patient with nodular regenerative hyperplasia and recurrent episodes of type B hepatic encephalopathy concomitant with PVT as well as CTPV, successfully treated with orthotopic liver transplantation. The portal inflow to the graft was carried out through the confluence of 2 thin paracholedochal varicose veins, obtaining good early graft function and recovery of the encephalopatic episodes. This alternative should be kept in mind as an option to assure hepatopetal splanchnic flow in those cases of diffuse thrombosis and cavernomatous transformation of portal vein.

Is Liver Biopsy Necessary in the Evaluation of a Living Donor for Liver Transplantation

BACKGROUND The role of liver biopsy in the evaluation of a candidate for living liver donation is controversial. Some authors suggest doing it routinely, but others do it only in selected cases. The aim of this work was to evaluate the usefulness of protocol liver biopsy in the evaluation of candidates for living liver donation. METHODS Ninety potential candidates for living liver donation were evaluated. In 46 cases donation was contraindicated without the need of liver biopsy. In the remaining 44 candidates, liver biopsy was done on a protocol basis. The usefulness of protocol biopsy was compared with the use of biopsy according to the recommendations of the Vancouver Forum. RESULTS Fifteen of the 44 biopsies were indicated according to the recommendations of the Vancouver Forum. Twelve of them were normal, and 3 had liver steatosis or steatohepatitis. Of the 29 biopsies done per protocol, 28 were normal and 1 showed liver steatosis. Donation was contraindicated according to liver biopsy findings in 3 of the 15 patients with liver biopsy done according to the Vancouver Forum recommendations and in none of the 29 patients with biopsy done per protocol (P = .034). CONCLUSIONS Protocol liver biopsy has a limited utility in the evaluation of the candidates for living liver donation.

Efficacy of Laparoscopic Approach in the Management of Early Liver Transplant Complications

The use of the laparoscopic approach in managing early liver transplant complications has been shown to be safe and feasible in various settings with the advantages of shorter recovery period, decreased postoperative pain, and rapid functional recovery. The laparoscopic approach has been used to resolve postoperative complications in kidney and pancreas recipients and less often in orthotopic liver transplantation (OLT) recipients, most of them in the late period (> 1 month posttransplantation). We herein describe our experience with the laparoscopic management of early complications after liver transplantation. From May 2009 to May 2011, we successfully treated three patients with early abdominal complications after OLT using a laparoscopic approach. Three patients-two with intraabdominal bleedings and one with a small bowel obstruction were treated successfully, thereby avoiding risks of a relaparotomy. In addition to these benefits, the laparoscopic approach causes less tissue injury and consequently evokes a minor innate immune response.

Applicability of Living Donor Liver Transplantation in a Program of Adult Liver Transplantation

INTRODUCTION The aim of this study was to investigate the applicability of living donor liver transplantation in a program of adult liver transplantation. PATIENTS AND METHODS We studied the outcomes of the evaluation of 71 potential donor candidates for 53 adult candidates to liver transplantation. RESULTS Ten of the potential donor candidates did not complete their evaluation. Among the remaining 61 potential donors, 29 (47.5%) were considered to be suitable donors. Only 17 (24% of the 71 initial candidates) underwent donation. The main causes for unsuitability for liver donation were a small remnant liver and vascular anatomic variants. CONCLUSION Fewer than 25% of potential liver donors became effective donors leading us to conclude that adult living donor liver transplantation has a low applicability.

Secuelas tras inyección ilegal de silicona líquida como técnica de aumento mamario: presentación de 2 casos

Resumen La utilizacion de silicona liquida con el fin de aumentar el volumen mamario tuvo una amplia difusion en la decada de los anos sesenta del siglo pasado, pero a finales de esta, tras la publicacion de numerosos estudios que describian la aparicion de un gran numero de complicaciones locales, asi como la migracion a distancia de pequenas cantidades de silicona, su practica se abandono. Su empleo dificulta posteriormente el diagnostico temprano del cancer de mama, por lo que este grupo de pacientes no debe incluirse en los programas habituales de cribado, sino que han de seguir controles periodicos y exhaustivos. En este contexto, la resonancia magnetica es la mejor prueba de imagen para la deteccion temprana de procesos malignos mamarios. La presencia de complicaciones locales, la sospecha de una lesion maligna o el deseo de la paciente por evitar ambas situaciones son indicacion de la mastectomia subcutanea.

Treatment of graft-versus-host disease with mesenchymal cells as a complication of a liver transplantation

We present the case of a liver transplant (LT) recipient donor who developed graft versus host disease (GVHD). The main features were cutaneous rash, diarrhea and pancytopenia. Mesenchymal cells were administered as part of the treatment. This is the first case of a patient with GVHD after LT reported to date. Despite the treatment, there was no improvement in aplasia or gastrointestinal symptoms and the patient died due to a disseminated infection.