Intratumoral injection of up to 3 x 10(12) viral particles of Ad.IL-12 to patients with advanced digestive malignancies is a feasible and well-tolerated procedure that exerts only mild antitumor effects.

Radioembolization (RE)‐induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low‐dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P < 0.0001). Treatment efficacy was not jeopardized since 3‐month disease control rates were virtually identical in both groups (66.7% and 67.2%, P = 0.93). Exposure to chemotherapy in the 2‐month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume <1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. Conclusion: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD. (HEPATOLOGY 2013)

Immunosuppression increases the risk of posttransplant malignancy and it may increase posttransplant mortality. The finding of factors related to the development of posttransplant malignancy may serve as a guide to avoid those risk factors and to develop strategies of posttransplant surveillance. The incidence and risk factors of malignancy were studied in 187 consecutive liver transplant recipients surviving more than 3 months. None of the 12 patients surviving less than 3 months had de novo neoplasia. The impact of malignancy on survival was studied in a casecontrol study. After a median follow-up of 65 months, 49 patients developed 63 malignancies: 25 patients had 35 cutaneous neoplasias and 27 patients had 28 noncutaneous malignancies. The 5-and 10-year actuarial rates of cutaneous neoplasia were 14 and 24% and the rates of noncutaneous neoplasia were 11 and 22%, respectively. Risk factors for the development of cutaneous malignancy were older age and Child-Turcotte-Pugh A status. Risk factors for the development of noncutaneous malignancy were older age, alcoholism, and smoking. Cutaneous neoplasia had no effect on survival, whereas patients with noncutaneous malignancy had a significant reduction of survival. The overall relative risk of cutaneous and noncutaneous neoplasia, as compared with the general population were 16.91 (95% confidence interval: 11.78-23.51) and 3.23 (95% confidence interval: 2.15-4.67), respectively. The relative risk of cancer-related mortality (after excluding recurrent malignancy) was 2.93 (95% confidence interval: 1.56-5.02). Multivariate analysis showed that noncutaneous malignancy was an independent risk factor for posttransplant mortality. In conclusion, liver transplant recipients have a higher risk of cancer-related mortality than the general population. This increased risk is due to the development of noncutaneous neoplasia. Older age, alcoholism, and smoking increase the risk of de novo noncutaneous neoplasia. (Liver Transpl 2005;11: 89-97.)

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.

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Our results suggest that besides impaired production in the failing liver, an increased TPO degradation by platelets sequestered in the congested spleen may contribute to thrombocytopenia in cirrhotic patients.

PurposeTo evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity.Patients and MethodsSeventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 × 106to 50 × 106cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals.ResultsFifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment.ConclusionIntratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy.

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