Metronomic capecitabine in advanced hepatocellular carcinoma patients: a phase II study.

UNLABELLED: Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. METHODS: This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. RESULTS: A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). CONCLUSION: Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib.

Sarcoidosis and sarcoid-like reaction associated with pancreatic malignancy: are you able to read a riddle?

CONTEXT: The sarcoidosis is an idiopathic multisystem inflammatory disease characterized by the presence of non-caseating granulomas in the affected organs. The clinical picture includes non-specific systemic symptoms and organ-specific symptoms, but it is frequently asymptomatic. Although not fully understood, a clear association between sarcoidosis and malignancies has been reported. In neoplastic patient, beside classical sarcoidosis, cases of sarcoid-like reaction have been extensively described, a condition characterized by the presence of non-caseating granulomas in the lymph nodes draining the tumor or, less commonly, in the distant lymph nodes; this is considered a benign non progressive condition, potentially regressive following neoplasm eradication. CASE REPORT: We report the first case of sarcoidosis/sarcoid-like reaction associated with neuroendocrine tumors of the pancreas. CONCLUSION: This clinical case highlights the difficulty and importance of differential diagnosis of lymphadenopathy in the management of neoplastic disease, and in view of the evolving clinical picture, if a distinction between sarcoidosis and sarcoid-like reaction is a clinical reality or if they is just represent different stage of the same disease. Therefore, we believe that a follow-up is necessary even in case of sarcoid-like reaction, since no data are reported in the literature on the long-term of this condition once treated the associated tumor.

Unexpected gamma glutamyltransferase rise increase during levetiracetam monotherapy.

Levetiracetam is an antiepileptic drug (AED) with a favourable tolerability profile with little or no effect on liver function. We describe an epileptic patient who developed a significant increase in gamma glutamyltransferase (gammaGT) while on levetiracetam monotherapy.

Efficacy of lamivudine therapy for advanced liver disease in patients with precore mutant hepatitis B virus infection awaiting liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) for end-stage liver disease resulting from hepatitis B virus (HBV) infection is associated with a high rate of recurrence and reduced survival. Lamivudine is effective in inhibiting HBV replication in patients with chronic hepatitis. This study evaluated the impact of lamivudine on viral suppression, liver function, and disease severity in patients awaiting OLT with HBV e-minus strain infection. METHODS: Twenty-five patients received lamivudine (100 mg per day) from the day of listing for OLT. All patients were positive for serum HBV-DNA by polymerase chain reaction and all had a Child-Pugh score of 7 or higher. RESULTS: Patients were followed for 12+/-9 months (mean +/- SD). Eleven underwent OLT within 13 months of treatment initiation, one died after 10 months, and one dropped out after 3 months. After 3, 6, and 9 months, HBV-DNA by polymerase chain reaction was undetectable in 14 of 25, 14 of 20, and 13 of 15 patients, respectively. Two patients developed lamivudine resistance after 9 and 18 months of treatment, respectively, without liver decompensation. Comparing baseline to last visit data, a significant improvement in prothrombin activity (43+/-15% vs. 52+/-19%; P=0.0014), serum bilirubin (3.4+/-1.9 vs. 2.5+/-2.2 mg/dL; P=0.0007), serum albumin (3.3+/-0.3 vs. 3.6+/-0.5 g/dL; P=0.0278), presence of ascites (15/25 vs. 7/25; P=0.0047), and Child-Pugh score (9 vs. 8; P=0.0003) was observed. Because of liver function improvement, four patients were placed on low priority status for OLT (United Network of Organ Sharing 3) and 9 on inactive status (United Network of Organ Sharing 7). The overall probability of survival at 6 and 12 months was 100% and 90.9%, respectively. CONCLUSIONS: Lamivudine has an important role in patients with end-stage liver disease caused by HBV precore mutant strain. Not only does HBV-DNA suppression allow patients to be eligible for OLT, but the improvement of the patients' clinical status may delay the need for OLT in an era of organ shortage.

Clinical effects of rifaximin in patientswith hepatic encephalopathy intolerant or nonresponsive to previous lactulose treatment: An open-label, pilot study.

BACKGROUND: Hepatic encephalopathy (HE) is a metabolic-neurophysiologicsyndrome that occurs in patients with advanced hepatic disease. One of the main pathogenic mechanisms is represented by circulating toxins produced by the intestinal metabolism of nitrogenous compounds. The therapeutic approach to HE is mainly based on drugs that eliminate ammonia-producing bacteria. OBJECTIVES: The aim of this study was to evaluate the effects of the nonabsorbable antibiotic rifaximin in patients with HE who were intolerant or nonresponsive to treatment with an oral, nonabsorbable disaccharide (lactulose). METHODS: This uncontrolled, open-label, pilot study was conducted at the University of Bologna, Bologna, Italy. Patients aged ≥ 18 years with histologically proven liver cirrhosis and HE were studied. All patients were intolerant or nonresponsive to previous treatment with lactulose. Rifaximin tablets were administered to patients at a dosage of 400 mg TID for 10 days. The portal systemic encephalopathy (PSE) index was evaluated at enrollment and at the end of the treatment period. Tolerability was assessed using hematology, biochemistry, and urinalysis and by recording adverse effects (AEs). RESULTS: Twenty-six patients (18 men, 8 women; mean [SD] age, 55.8 [8.0] years) were enrolled (intolerants, n = 17; nonresponders, n = 9). All patients completed the study. Significant improvement was shown in most of the 5 components of the PSE index after rifaximin administration in both intolerants and nonresponders. At the end of the 10-day treatment period, the PSE index was significantly reduced in both intolerants and nonresponders. Rifaximin was well tolerated; no clinically relevant AEs were observed during the treatment period. CONCLUSIONS: This pilot study of patients with liver cirrhosis and HE who were intolerant or nonresponsive to previous treatment with an oral, nonabsorbable disaccharide suggests that treatment with rifaximin may be considered as an adjuvant or an alternative treatment in reducing HE.

Transcatheter embolization for giant splenic artery aneurisms: still an open question.

Transcatheter embolization is the mainstay of the therapy of splenic artery aneurysms (SAAs) in patients with portal hypertension. It is indicated when the SAA diameter reaches 20 mm. Although endovascular techniques are effective and safe for the treatment of medium-sized SAAs, little is known about their applicability to large-sized SAAs. Herein, we report a case of giant SAA, which was treated with transcatheter coil embolization. The case was not considered suitable for surgery because of the presence of severe portal hypertension. The procedure was complicated by bacterial infection of the coils within the aneurismatic sac, leading to the development of hepatic failure. A liver transplant was then successfully performed despite the presence of a nonresponsive infection.

Liver Cirrhosis in a Patient with Sickle Cell Trait (Hb Sß Thalassemia) without Other Known Causes of Hepatic Disease.

Liver involvement in patients with sickle cell anemia/trait includes a wide range of alterations, from mild liver function test abnormalities to cirrhosis and acute liver failure. Approximately 15-30% of patients with sickle cell anemia present cirrhosis at autopsy. The pathogenesis of cirrhosis is usually related to chronic hepatitis B or C infection or to iron overload resulting from the many transfusions received by these patients in their lifetime. Thus, cirrhosis has been described almost exclusively in patients with sickle cell anemia, while only mild liver abnormalities have been associated with the sickle cell trait. In the present case study, we describe a young Mediterranean man carrying a sickle cell trait (Hb Sß(+) thalassemia) who developed liver cirrhosis being negative for hepatitis C and B viruses or for other causes of cirrhosis and not receiving chronic blood transfusions.

Sleep disturbance and daytime sleepiness in patients with cirrhosis: a case control study.

Sleep disturbance and excessive daytime sleepiness have been reported in patients with hepatic cirrhosis. The objective of this study was to evaluate daytime somnolence and sleep complaints in a group of 178 patients with cirrhosis compared to a control group. Sleep features and excessive daytime sleepiness were evaluated by the Basic Nordic Sleep Questionnaire (BNSQ) and the Epworth Sleepiness Scale (ESS). We collected clinical and laboratory data, neurological assessment and EEG recordings in cirrhotic patients. Patients with cirrhosis complained of more daytime sleepiness (p<0.005), sleeping badly at least three times a week (p<0.005), difficulties falling asleep (p<0.01) and frequent nocturnal awakening (p<0.005) than controls. We found a poor correlation between sleep disorders and clinical or laboratory parameters. Our results confirm previous literature reports suggesting a high prevalence of sleep disturbance in patients with cirrhosis. Insomnia and daytime sleepiness are the main complaints. Sleep disorders are probably a multifactorial phenomenon.

Incidence of gallstone disease in Italy: results from a multicenter, population-based Italian study (the MICOL project).

AIM: To evaluate gallstone incidence and risk factors in a large population-based study. METHODS: Gallstone incidence and risk factors, were evaluated by structured questionnaire and physical examination, respectively, in 9611 of 11 109 (86.5%) subjects who were gallstone-free at the cross-sectional study. RESULTS: Six centers throughout Italy enrolled 9611 subjects (5477 males, 4134 females, aged 30-79 years), 9517 of whom were included into analysis: 424 subjects (4.4%) had gallstones and 61 (0.6%) had been cholecystectomized yielding a cumulative incidence of 0.67% per year (0.66% in males, 0.81% in females). Increasing age, a high body mass index (BMI), a history of diabetes, peptic ulcer and angina, and low cholesterol and high triglyceride levels were identified as risk factors in men while, in females, the only risk factors were increasing age and a high BMI. Increasing age and pain in the right hypocondrium in men and increasing age in females were identified as predictors of gallstones. Pain in the epigastrium/right hypocondrium was the only symptom related to gallstones; furthermore, some characteristics of pain (forcing to rest, not relieved by bowel movements) were significantly associated with gallstones. No correlation was found between gallstone characteristics and clinical manifestations, while increasing age in men and increasing age and BMI in females were predictors of pain. CONCLUSION: Increasing age and BMI represent true risk factors for gallstone disease (GD); pain in the right hypocondrium and/or epigastrium is confirmed as the only symptom related to gallstones.