Differences in the incidence and clinical evolution of early neurotoxicity after liver transplantation based on tacrolimus formulation used in the immunosuppressive induction protocol.

INTRODUCTION: Posttransplant early calcineurin inhibitor (CNI)-induced neurotoxicity (ECIIN) was related to high CNI levels, among other factors. Minimizing exposure could modify its incidence or clinical evolution. OBJECTIVE: To compare the incidence, predisposing factors, and clinical evolution of ECIIN after immunosuppressive induction with low-dose tacrolimus-MR (Advagraf) or conventional dose tacrolimus (Prograf). PATIENTS AND METHODS: We matched 71 patients treated with an immunosuppression induction schedule with basiliximab and low doses of Advagraf (cases group) 1:1 by recipient age and indication for liver transplantation (OLT) with patients treated with a conventional tacrolimus regimen (control group). Baseline characteristics, liver and kidney function, operative technical characteristics, kidney function, and C0 tacrolimus levels at several time points after liver OLT were analyzed. RESULTS: There were 31 cases of ECIIN (21%), 14 in the cases group (20%) and 17 in the control group (24%; P < .001). The incidence of ECIIN was higher in alcoholic liver disease (odds ratio [OR], 8.2; 95% CI, 2.3-28.6; P < .001) and past history of encephalopathy (OR, 2.6; 95% CI, 1.16-5.9; P < .02). Among cases, the incidence of ECIIN was higher when encephalopathy signs were present at time of transplantation (36% vs 12%; P < .001). Control of ECIIN required a switch to cyclosporine therapy in all those in the cases group, whereas this was only needed for 9 cases in the control group (47%; P < .001). CONCLUSION: In this study, although the incidence rate of neurotoxicity induced by Advagraf was lower than the induced by Prograf, it did not respond to routine treatment and required a significantly higher rate of switch to cyclosporine for its control.

Late recurrence of hepatocellular carcinoma after liver transplantation: is an active surveillance for recurrence needed?

INTRODUCTION: Liver transplantation (OLT) is considered the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rates, when restrictive selection criteria are applied. Nevertheless, tumor recurrence may occur in 3.5% to 21% of recipients. It usually occurs within 2 years following OLT, having a major negative impact on prognosis. The efficacy of active posttransplantation surveillance for recurrence has not been demonstrated, due to the poor prognosis of recipients with recurrences. AIM: To analyze the clinical, pathological, and prognostic consequences of late recurrence (>5 years after OLT). METHOD: We analyzed the clinical records of 165 HCC patients including 142 males of overall mean age of 58 ± 6.9 years who underwent OLT between July 1994 and August 2011. RESULTS: Overall survival was 84%, 76%, 66.8%, and 57% at 1, 3, 5, and 10 years, respectively. Tumor recurrence, which was observed in 18 (10.9%) recipients, was a major predictive factor for survival: its rates were 72.2%, 53.3%, 26.7%, and 10% at 1, 3, 5, and 10 years, respectively. HCC recurrence was detected in 77.8% of patients within the first 3 years after OLT. Three recipients (100% males, aged 54-60 years) showed late recurrences after 7, 9, and 10 years. In only one case were Milan criteria surpassed after the examination of explanted liver; no vascular invasion was detected in any case. Recurrence sites were peritoneal, intrahepatic, and subcutaneous abdominal wall tissue. In all cases, immunosuppression was switched from a calcineurin-inhibitor to a mammalian target of rapamycin inhibitor. We surgically resected the extrahepatic recurrences. The remaining recipient was treated with transarterial chemoembolization with doxorubicin-eluting beads and sorafenib. Prognosis after diagnosis of recurrence was poor with median a survival of 278 days (range, 114-704). CONCLUSIONS: Global survival, recurrence rate, and pattern of recurrence were similar to previously reported data. Nevertheless, in three patients recurrence was diagnosed >5 years after OLT. Although recurrence was limited and surgically removed in two cases, disease-free survival was poor. Thus, prolonged active surveillance for HCC recurrence beyond 5 years after OLT may be not useful to provide a survival benefit for these patients.

Strategies of immunosuppression for liver transplant recipients with hepatocellular carcinoma.

Liver transplantation is considered to be the most efficient therapeutic option for patients with liver cirrhosis and early stage hepatocellular carcinoma (HCC) in terms of overall survival and recurrence rate. The application of restrictive selection criteria based on tumor size and number of nodules is advised to obtain optimal results. Nevertheless, tumor recurrence occurs in 3.5% to 21% of recipients, despite careful pretransplant staging and patient selection. Post transplant recurrence of hepatocarcinoma clearly has a major negative impact on prognosis. Intuitively, an immunosupressed state is undesirable in cancer patients. Inversely, modulation or minimization of immunosuppressive therapy could influence tumor progression and reduce the negative impact of recurrence on posttransplant survival. Experimental evidence shows that mammalian target of rapamycin (mTOR) inhibitors have antiangiogenic and antiproliferative effects. Thus, their application has been proposed as antineoplastic agents for immunosuppressive protocols in liver transplant recipients with HCC and may reduce the rate or the impact of tumor recurrence. Clinical data about efficacy and safety of mTOR-based immunosuppressant protocols in liver transplant recipients with HCC show promising results, namely low recurrence and higher survival rates compared with standard calcineurin inhibitor-based immunosuppressive protocols, even among patients with extended morphological criteria. The safety profile is regarded generally as adequate.

Viral and host factors related with histopathologic activity in patients with chronic hepatitis B and moderate or intermittently elevated alanine aminotransferase levels.

OBJECTIVE: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. PATIENTS AND METHODS: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 10³ IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥2 or fibrosis ≥2 according to Scheuer Classification. RESULTS: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNA-HBV > 2 x 10³ IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). CONCLUSION: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases.

Influencia de factores virales y del huésped en la actividad histológica en pacientes con hepatitis crónica por virus de la hepatitis B y elevación moderada o intermitente de alanina aminotransferasa / No disponible

Objetivo: analizar factores virales y del huésped relacionados con actividad histológica en un subgrupo de pacientes con hepatitis crónica B y elevación intermitente o moderada de alanina aminotransferasa (ALT), y el umbral que determine daño histológico indicativo de tratamiento. Pacientes y métodos: análisis retrospectivo de parámetros virales y del huésped en 89 pacientes con hepatitis crónica B biopsiados consecutivamente por elevación intermitente o moderada de ALT [1-2 x USN (USN = 39 UI/ml)]. Fueron analizados edad, sexo, ALT, HBeAg, carga viral y genotipo. Se consideró como lesion histológica avanzada un Índice de Knodell (IK) > 7, e indicativa de tratamiento la inflamación lobulillar ≥ 2 o fibrosis ≥ 2 según la clasificación de Scheuer. Resultados: existió un IK > 7 y lesión indicativa de tratamiento en 47,8 y 60,7%, respectivamente. La edad, sexo varón, ALT y carga viral se relacionaron con lesión avanzada (p < 0,05). La frecuencia de lesión indicativa de tratamiento fue mayor en pacientes con ALT > USN (69,1 vs. 47,1%, p = 0,04). La frecuencia de lesión avanzada no fue significativamente mayor cuando se consideraron como puntos de corte la edad de 40 años o ADNVHB > 2 x 103 UI/ml o positividad de HBeAg. Se observó menor actividad histológica en pacientes con genotipo D respecto a aquellos infectados con otros genotipos (p < 0,05). Conclusión: una mayor frecuencia de lesión avanzada en pacientes con hepatitis crónica B y elevación intermitente o moderada de ALT hacen recomendable la biopsia hepática independientemente de la carga viral y positividad de HBeAg. Factores como la edad, sexo o genotipo pueden ayudar de forma individual a dicha indicación(AU)

Objective: viral and host factors are related with progression of pathological lesion in chronic hepatitis B. We analyzed these factors in patients with moderate or intermittently elevated ALT levels, and its threshold that determinate significant histological activity. Patients and methods: retrospective analyses of viral and host parameters in 89 consecutive chronic hepatitis B patients biopsied because of moderate or intermittently elevated ALT levels [1-2 x ULN (ULN = 39 IU/ml)] and/or DNA-HBV > 2 x 103 IU/ml in AntiHBe+ patients. It was analyzed age, gender, ALT levels, HBeAg, viral load and genotype. It was considered advanced histological lesion a Knodell Score (KS) > 7 and histological lesion indicating treatment, lobular inflammation ≥ 2 or fibrosis ≥ 2 according to Scheuer Classification. Results: KS > 7 and histological lesion indicating treatment was found in 47.8 and 60.7% respectively. It was observed relationship between age, male gender, ALT levels and viral load with histological damage (p < 0.05). Frequency of advanced lesion indicating treatment was upper in patients with ALT levels > ULN (69.1 vs. 47.1%, p = 0.04). There were not significant upper frequencies of advanced lesion when a cut-off of 40 years or DNAHBV > 2 x 103 IU/ml viral load or serological status HBeAg was considerate. Histological activity was lesser in genotype D patients than those infected with others genotypes (p < 0.05). Conclusion: upper frequency of advanced histological lesion in chronic hepatitis B patients with moderate or intermittently elevated ALT levels make recommended liver biopsy, independent of viral load and serological status HBeAg. Other factors like age, gender or genotype can help to indicate biopsy in individual cases(AU)

Valganciclovir-induced leukopenia in liver transplant recipients: influence of concomitant use of mycophenolate mofetil.

INTRODUCTION: An increased incidence and magnitude of leukopenia during concomitant treatment with valganciclovir (VGC) and mycophenolate mofetil (MMF) has been reported. OBJECTIVE: To evalute the incidence and severity of leukopenia and neutropenia among liver recipients treated with VGC and related factors. PATIENTS AND METHODS: Retrospective analysis of clinical and analytical data related to leukopenia (<3000 leukocytes/mm(3)) and neutropenia (<900 neutrophils/mm(3)) in liver transplant patients who were treated with VGC from 2003 to 2007. We examined the influence of concomitant administration of MMF and development of subsequent infections. RESULTS: Among 209 liver transplants, 40 treatments with VGC were prescribed in 37 patients (17.7%), 12 of which (30%) were associated with MMF. The patients has an average age of 49.7 +/- 12.7, body mass index (BMI) of 27.28 +/- 5.17, and Model for End-stage Liver Disease Score (MELD) 12.45 +/- 7.5. The daily average dose of VGC was 1440 +/- 446.5 mg and MMF, 1454.5 +/- 350.3 mg. We observed a decrease of 30% in initial leukocyte count (5353.7 +/- 2706.6) and 40% in neutrophil count (3600 +/- 2182.1). With no relationship to total dose or BMI-adjusted dose of VGC nor concomitant administration of MMF. The initial leukocyte count was significantly lower (4411 +/- 1930 vs 6206 +/- 3053; P = .03) and underwent a main drop (2344.7 +/- 1974.3 vs 898.1 +/- 2435.6; P = .04) when leukopenia developed. In the induced neutropenia group, previous leukocyte count (3797.1 +/- 1223.9 vs 5683.9 +/- 2829.3; P = .01), MELD (18.7 +/- 8.8 vs 11.1 +/- 6.6; P = .01), and the creatinine pretreatment (1.44 +/- 0.4 vs 1.09 +/- 0.3; P = .01) were significantly different. Subsequent infections induced by the leukopenia were not observed. CONCLUSIONS: In our series, the concomitant use of VGC and MMF was not associated with a greater incidence of leukopenia and/or neutropenia than VGC administration alone. Previous leukocyte count was associated with them. MELD and renal dysfunction are factors related to severe neutropenia. Leukopenia was not associated with a greater incidence of infections.

Quiste linfoepitelial: una causa muy infrecuente de masa pancreática / No disponible

No disponible

Absceso subfrénico con extensión pleural y subcutánea como complicación de un cálculo vertido al peritoneo durante la colecistectomía laparoscópica: implicaciones terapéuticas / Subfrenic abscess with pleural and subcutaneous involvement as complication of peritoneal gallstone dropped during laparoscopic cholecystectomy: therapeutic implications

No disponible

Trasplante hepático en el hepatocarcinoma: criterios expandidos de California / No disponible

No disponible

Push-enteroscopy series: diagnostic and therapeutic efficacy.

OBJECTIVE: To analyse the diagnostic efficacy of oral push-type enteroscopy (PE) according to indications. To assess evolution in patients with occult gastrointestinal bleeding (OGIB) according to findings and endoscopic therapy. METHODS: 204 PE performed in 167 patients: OGIB: 117, Crohn's disease: 34, radiological abnormalities: 21; chronic diarrhoea: 12; intestinal sub-occlusion: 11; polyposis: 7; other: 2. We followed clinical outcome in 72 patients after PE for OGIB. They were separated according to findings and endoscopic therapy: no findings: 32; no treated angiodysplasia: 10; treated angiodysplasia: 20; other lesions: 10. We evaluated the number of admissions and transfusional requirements before and after PE, re-bleeding and surgical treatment. Statistics were performed using Student's t test and Chi-square test (statistical significance p < 0.05). RESULTS: We diagnosed lesions in 65.8% PE for OGIB, angiodysplasia being the more frequent finding (33.3%). We found lesions before Treitz in 15.4% A higher diagnostic efficacy was seen in active bleeding (83.4%) versus anaemia (52.2%), p < 0.05. After PE both admissions and transfusional requirements decreased in all subgroups specially in treated angiodysplasias and other lesions, nearly reaching statistical significance (p = 0.07). Re-bleeding occurred in 50% of non-treated lesions versus 20-25% in treated lesions. We found lesions in 47% of PE for Crohn's disease, in 52.4% for radiological abnormalities, in 41.6% for chronic diarrhoea and in 0% for intestinal sub-occlusion. CONCLUSIONS: PE is efficient in the diagnosis and therapy of patients with OGIB, Crohn's disease and radiological abnormalities. Its usefulness is controversial in the study of chronic diarrhoea and intestinal sub-occlusion.

Eficacia diagnóstica y terapéutica en una sere de enteroscopia de pulsión oral / Push-enteroscopy series: diagnostic and therapeutic efficacy

Objetivo: analizar la eficacia diagnóstica de la videoenteroscopia de pulsión oral (VPO) según la indicación y la evolución de pacientes con hemorragia digestiva de origen oscuro (HDOO) según hallazgos y tratamiento endoscópico. Métodos: 204 VPO realizadas a 167 pacientes: HDOO: 117; enfermedad de Crohn: 34; anormalidades radiológicas: 21; diarrea crónica: 12; suboclusión intestinal: 11; poliposis: 7; otros: 2.Fueron seguidos 72 pacientes tras VPO por HDOO dividiéndolos según hallazgos y tratamiento endoscópico: sin hallazgos: 32; angiodisplasias no tratadas: 10; tratadas: 20; lesiones distintas a angiodisplasias: 10. Se valoró el número de ingresos y requerimientos trasfusionales pre y post-VPO, resangrados y cirugía. Estudio estadístico mediante t de Student y Chi cuadrado (significación estadística p<0,05). Resultados: se diagnosticaron lesiones en 65,8 por ciento VPO por HDOO, siendo las angiodisplasias las más frecuentes (33,3 por ciento) y las lesiones pre-Treitz (15,4 por ciento). Existe tendencia a mayor eficacia diagnóstica en pacientes con sangrado activo (83,4 por ciento) frente anemia (52,2 por ciento) alcanzando significación estadística p<0,05. Tras VPO disminuyen los ingresos y requerimientos trasfusionales en todos los grupos, más en el de angiodisplasias tratadas y otras lesiones sin alcanzar significación estadística p=0,07. Resangró el 50 por ciento de pacientes con lesiones no tratadas frente un 20-25 por ciento en tratados. Se observaron lesiones en 47 por ciento de VPO por enfermedad de Crohn, 52,4 por ciento por alteraciones radiológicas, 41,6 por ciento por diarrea crónica y 0 por ciento por suboclusión intestinal. Conclusión: la VPO es eficaz en el diagnóstico y tratamiento de pacientes con HDOO, enfermedad de Crohn y alteraciones radiológicas, siendo cuestionable su utilidad en estudio de diarrea crónica y suboclusión intestinal (AU)

Liver transplantation for type Ib glycogenosis with reversal of cyclic neutropenia.

We describe a case of glycogen storage disease type Ib in 32-year old male patient with poor metabolic control in spite of medical and nutritional management and the use of recombinant granulocyte stimulating factor. Because of this, liver transplantation was considered as a definitive treatment. We comment on the metabolic results of liver transplantation performed, with reversal of hypoglycemia, hyperuricemia, hypertriglyceridemia and cyclic neutropenia, all of which persist 4 years post-transplant. In view of this case, we believe that liver transplantation is a feasible option to consider in patients with type Ib glycogenosis as a definitive therapeutic procedure.

[Incidence of malignancy in millimetric polyps]. / Incidencia de malignidad en los pólipos milimétricos.

This paper is based on the analysis of 178 polyps of 5 mm or less (polyps we have termed "millimetric") studied in the Endoscopy Department of "La Paz" Hospital, Madrid, during 1993. All polyps fulfilling these characteristics detected during this period are included. The 178 polyps represent 43.4% of all polyps (N = 410) found on colonoscopy in this department in this period. The variables considered in the study protocol include age, sex, localization, morphology and histological examination, with particular attention to high risk histological lesions such as signs of possible malignancy.; we also performed a comparative study between the results obtained from the 178 millimetric polyps (Group I) and the 232 polyps greater than 5 mm (Group II) obtained during the same period. The endoscopic technique for the resection of the polyps was evaluated together with its possible complications. Although there were no significant differences found in respect to age, sex and location, there were morphological differences with a greater number of pediculated or semi-pediculated polyps in Group I whilst there were more sessile polyps in Group II. Adenomatous polyps were the most frequent (84%) in both groups. There was a greater incidence of signs of possible early malignant changes in Group II polyps (10) than in Group I (3.3%). The conclusions which may be drawn from our study are that it is clinically advisable to excise all polyps of 5 mm or less as the frequency of high risk histological changes is not negligible (3.3%), and excision is not problematic as the technique is easy and there have been no complications in our series.

[Hepatocellular carcinoma: is spontaneous regression possible?]. / Carcinoma hepatocelular: es posible la regresión espontánea?

We present the case of a patient with liver cirrhosis secondary to hepatitis C who developed a large (6 cms) hepatocellular carcinoma, diagnosed by raised alphafetoprotein (AFP) levels (> 10000 ng/ml) and imaging techniques (ultrasonography and abdominal CT with and without contrast). During follow-up there was normalization of the AFP levels and disappearance of the lesion on U.S. and CT. Spontaneous regression is exceptional in hepatocellular carcinoma. We describe the characteristics of our case and of the 10 patients described in the literature.

[Melanoma of the small intestine and adenocarcinoma of the colon]. / Melanoma de intestino delgado y adenocarcinoma de colon.

The clinical case of a 73-years old male who was admitted for diarrhea and loss of weight is presented. Barium enema and colonoscopy demonstrated small size polyps in the sigmoid colon, one of which had a histologic diagnosis of adenocarcinoma. Abdominal examination detected a mass in the mesohypogastrium which did not appear to be related to the previous findings. CAT and intestinal transit confirmed a second tumor in the small bowel with the histologic diagnosis of a resected specimen being melanoma.