Role of Transarterial Chemoembolization to Downstage Hepatocellular Carcinoma Within the Milan Criteria.

The practice of treating candidates for liver transplantation (LT) for hepatocellular carcinoma (HCC), with locoregional therapies, is common in most transplantation centers. We present our results using transarterial chemoembolization (TACE) as a neo-adjuvant treatment in our center between 2002 and 2013 to determine its effectiveness in downstaging (DS) HCC within the Milan criteria (MC). Clinical variables were recorded of both donors and recipients, such as diagnosis and treatment, variables related to its etiology, the use of TACE as a neo-adjuvant treatment, immunosuppressive therapy, toxicity, recurrence of disease, exitus, and others. Sixty-four patients were analyzed. Median age was 57 (range, 51-64) years. In this study, 84% (54) were male and 16% (10) were women. Etiology of HCC was viral in 47% (30), alcoholic in 25% (16), and other in 28% (18). TACE was conducted in 45 patients (70%). Every patient included in our study presented a T2 stage (of tumor-nodes-metastasis [TNM]) before surgery, thus within the MC. However, DS protocol was performed in 5 patients (7.8%). We performed a bivariate analysis, having assessed that the use of TACE decreases T2 stage into T1-T0 stage (P < .05). We have also calculated the recurrence-free survival, which reaches up to 80% to 125 months. Furthermore, even though the statistical differences are not consistent due to the simple size presented, we conclude that TACE is a safe and effective therapy to control HCC progression during the waiting list time.

Transoral robotic surgery of the central skull base: preclinical investigations.

In this study we explored possible applications of the da Vinci system in approaching the skull base at optic chiasm level on two cryopreserved cadavers, using an entirely transoral robotic technique (TORS). We used a standard 12 mm endoscopy and 8 mm terminals. Bone drilling was performed manually. The da Vinci system is equipped with very good illumination and 3D viewing, thus providing excellent vision and great maneuverability even in the less accessible areas of the skull. Our experience demonstrates that an entirely transoral skull base robotic approach to this complex anatomical region has many advantages as compared to traditional techniques.

Echocardiographic study in cirrhotic patient candidates for liver transplantation.

We studied 81 cirrhotic patients who were candidates for liver transplantation to evaluate frequently detected cardiac alterations by echocardiographic study. Patients were distributed into three groups: group 1 comprised alcoholic cirrhotic patients (n = 40); group 2, viral cirrhotic patients (hepatitis C or B virus) (n = 35); and group 3, patients with primary biliary cirrhosis (n = 6). Cardiac chambers and diastolic functions were estimated by two-dimensional transthoracic echocardiography in M mode and Doppler. The most frequently detected cardiac structural alterations were left atrial diameter enlargement in 100% of the women and 40% of the men in group 1; 87.5% of the women and 15.4% of the men in group 2; and 33.3% of the women in group 3. Interventricular wall thickness enlargement in 50% of the women and 27.8% of the men in group 1, 25% of the women and 30.8% of the men in group 2, and 16.4% of the women in group 3. The prevalence of diastolic dysfunction was 45% in group 1, 32.3% in group 2, and 16.4% in group 3 (P > .05). There were no significant differences between the groups in cardiac chamber dimensions, left ventricular wall thickness, or prevalence of diastolic dysfunction.

Hepatopulmonary syndrome among cirrhotic candidates for liver transplantation.

This study assess of hepatopulmonary syndrome (HPS) prevalence and the influence of etiology among cirrhotic patients due to an alcoholic or viral etiology. We examined the records of patients were distributed as Group 1, alcoholic (n = 40) and Group 2, hepatic cirrhosis of viral etiology (n = 35). Hepatic cirrhosis status was estimated by CHILD and MELD scores. Presence of clinical ascites spell out was noted as well as size and diastolic functions of the cardiac chambers using two-dimensional transthoracic echocardiography in M mode and by Doppler. HPS was studied with agitated saline serum and intravenous contrast administration. HPS was considered to be present when serum or contrast passed to the left chamber before the 5th cardiac cycle. There was no significant differences among related to sex, age, cirrhosis status or ascites. HPS frequency was 35% in Group 1 versus 64.7% among Group 2-Patients (P = .01). Taking into account the results, we concluded that HPS frequency was related to cirrhotic etiology. Upon multivariate analysis a patients with cirrhosis from viral etiology showed significantly increased HPS frequency compared with those displaying cirrhosis of an alcoholic etiology.

Liver transplantation for hepatocellular carcinoma: results of a multicenter study with common priorization criteria.

OBJECTIVE: To evaluate the results of liver transplantation (OLT) performed for hepatocellular carcinoma (HCC) among a multicenter cohort of patients with predefined common inclusion and priorization criteria. PATIENTS AND METHODS: Over a 5-year period (January 2002-December 2006), 199 HCC patients underwent OLT in four centers in Andalusia. The morphological (Milan) inclusion criteria were priorized in two consecutive periods, according to the Model for End-stage Liver Disease score: group I, 53 patients (HCC < 2 cm = 24 points; > or = 2 cm or multinodular = 29 points) and group II, 146 cases (HCC < 3 cm without priorization; HCC > or = 3 cm or multinodular = 18 points). RESULTS: Among the 199 HCCs, 186 (93.5%) subjects were transplanted and 13 (6.5%) were excluded. There were 18 cases (9.7%) where the diagnosis was incidental and 168 were known HCC cases; 144 (85.7%) complied with the Milan criteria (Milan+); 24 (14.3%) exceeded there criteria (Milan-). According to preoperative imaging, the number of nodules and tumor mean sizes among the excluded-Milan+ and Milan- groups-were 1.8/5.3 cm, 1.4/3.5 cm, and 2.3/6.7 cm, respectively (P < .001). Percutaneous treatment during listing was delivered to 55% of the excluded cases: 49% of Milan+ and 96% of Milan-. The median time on the list was 88 days for known HCC (53 days for group I, and 97 days for group II), and 172 days for the incidental HCCs. Staging (pTNM) was correct in 64% of cases: 23% were understaged and 13% were overstaged. Overall mortality within the first 90 days was 9%, and transplant patient survival at 5 years was 61%. No differences were observed in survival rates between both study periods, although there were differences between the Milan+ (65%) and Milan- (23%) groups (P < .04). In addition, the difference in the recurrence rates was also significant between the Milan+ (7%), Milan- (24%), and the incidental (25%) groups (P < .02). CONCLUSIONS: A common priorization policy of HCC for OLT based on morphological criteria results in a low exclusion rate on the waiting lists (6.5%). The Milan criteria are still a good cutoff to stratify the risk of recurrence, despite preoperative tumor staging being correct in only two-thirds of cases.

Mycophenolate mofetil-induced neutropenia in liver transplantation.

BACKGROUND: Mycophenolate mofetil (MMF) is a potent, safe immunosuppressive agent for rescue therapy of acute and chronic rejection in orthotopic liver transplant recipients. It helps to reduce the serious toxic side effects of calcineurin inhibitors (CNIs). The side effects of MMF, such as bone marrow toxicity, have been reported. Herein we report four patients who underwent liver transplantation and developed neutropenia while receiving MMF. METHODS: Between April 2002 and October 2003, we performed 24 liver transplants in 25 patients. Eighteen patients were given MMF for the following reasons: renal failure in nine (50%); treatment of acute rejection in three (16.6%); primary prophylaxis of rejection in five (27.7%); and CNI withdrawal in one (5.5%). RESULTS: Of the 18 patients treated with MMF, there were 11 men (61.1%) and seven women (38.8%), with an overall mean age of 55.5 years. This therapy was ceased in four patients due to neutropenia (22%). Discontinuation of MMF was followed by a rapid and spontaneous rise in neutrophils in two patients. Granulocyte colony stimulating factor (GCSF) was administered to one patient and in another a bone marrow biopsy was performed due to persistent anemia, leukopenia, and thrombocytopenia. The mean time from starting MMF to the development of neutropenia was 4 months. Only the third patient showed elevated levels of MMF. CONCLUSIONS: MMF is a potent immunosuppressive agent in liver transplantation. However, because serious hematologic toxicity has been reported, we recommend caution in administration and careful monitoring of blood levels.

Body composition in 10 to 14-year-old handball players / Composición corporal en jugadores de balonmano de 10 a 14 años

This study analyses the body composition of male school children with an age range of 10-14: players from 11 league teams. The sample corresponds to 29.32% of the total population (854) and enabled us to find highly reliable conclusions. Besides the 5 specific data, we measured eight skinfolds, six lengths, eight heights, thirteen girths or perimeters, and nine diameters. The study of body composition was done following Matiegka's method. The percentage of fat mass was estimated using the equation of Slaughter et al; muscle mass by the Drinkwater and Ross formula; bone mass by Rocha's formula and residual mass by Würch's equation. The results show that these athletes are taller, weigh more and have a larger span than the athletes of other papers. From ages 10 to 14, the percentage of fat mass decreases, and a change in the distribution of subcutaneous fat is observed (AU)

Se estudia la composición corporal de escolares, sexo masculino, de 10 a 14 años de edad, jugadores de once equipos federados. La muestra corresponde al 29.32 per cent del total de la población (854) que permite dictaminar unas conclusiones de gran fiabilidad. Además de los 5 datos específicos se han hecho ocho pliegues, 6 longitudes; 8 alturas; 13 perímetros y 9 diámetros. El estudio de composición corporal se ha hecho por el método tetracompartimental de Matiegka. El porcentaje de masa grasa se ha obtenido usando la fórmula de Slaughter y col., la masa muscular por la fórmula de Drinkwater y Ross, la masa ósea por la fórmula de Rocha y la masa residual por la fórmula de Würch. Los resultados describen que estos deportistas son más altos, tienen más peso y más envergadura que los atletas de otros artículos semejantes. Desde los 10 hasta los 14 años, disminuye el porcentaje de masa grasa y cambia la distribución de la grasa subcutánea (AU)

Estudio multicéntrico retrospectivo de la respuesta al interferón en la hepatitis crónica por VHB / Multicenter retrospective study of response to interferon in choric hepatitis B

OBJETIVO: el fármaco más ampliamente utilizado en el tratamiento de la hepatitis crónica B ha sido el interferón alfa, con unas tasas de respuesta del 25-40 por ciento. Los objetivos a corto plazo del tratamiento son inducir la eliminación de los marcadores de replicación viral en suero, reducir los niveles de transaminasas y mejorar la histología hepática. Son factores predictores de respuesta unos niveles elevados de transaminasas, una concentración baja de DNA-VH13 y signos de actividad histológica fundamentalmente. Los objetivos de este estudio han sido conocer de forma retrospectiva la respuesta al INF-a en pacientes con hepatopatía crónica por VHB, de forma global y según el HBeAg, así como analizar los factores predictores de respuesta al mismo. PACIENTES Y MÉTODOS: hemos realizado un estudio multicéntrico retrospectivo de la respuesta al interferón alfa en 132 pacientes con hepatopatía crónica por el virus B, tanto de forma global como teniendo en cuenta el HBeAg y analizado los factores predictores de respuesta al mismo. RESULTADOS: globalmente, 59 pacientes (45 por ciento) tuvieron respuesta completa mantenida al INF, 61 (46 por ciento) no respondieron y 12 (9 por ciento) recidivaron. Ninguno negativizó el HBsAg. En los pacientes HBeAg+, 30 pacientes respondieron de forma mantenida (46 por ciento), 22 no respondieron (49 por ciento) y tres (5 por ciento) recidivaron, siendo similar en los casos HBeAg- (43, 43 y 14 por ciento, respectivamente). De todos los parámetros estudiados sólo las transaminasas sirvieron para predecir la respuesta global, observando en los pacientes con respuesta completa mantenida unas cifras significativamente más altas que en los no respondedores. En los HBeAg+ sólo la edad fue predictora de respuesta y en los HBeAg- la histología. El sexo, el antecedente epidemiológico, tipo de IFN, dosis, tiempo de tratamiento y tipo de virus no tuvieron influencia en la respuesta. CONCLUSIONES: hemos observado una respuesta mantenida global al IFN del 45 por ciento con una tasa de seroconversión (AU)

Multicenter retrospective study of response to interferon in chronic hepatitis B.

AIM: The only agent known to have a lasting beneficial effect in chronic hepatitis B is interferon alpha, which achieves long-term remission in 25-40% of the patients. The goals of treatment are to induce clearance of HBV DNA from serum, to return serum aminotransferases to normal, and to improve histological findings in the liver. The most important factors predictive of response to treatment are high serum aminotranferases levels, low serum HBV DNA concentrations, and active histologic changes on liver biopsy. The aim of this study was to assess the response to interferon alpha in patients with chronic hepatitis B and to analyze the factors predictive of response. METHODS: We conducted a multicenter retrospective study to investigate the effect of interferon treatment in 132 patients with chronic hepatitis B in overall terms and based on HBeAg, and factors predictive of response. RESULTS: A overall sustained response was noted in 59 of 132 interferon-treated patients (45%) and 61 patients were nonresponders (46%). 12 patients relapsed (9%). None of the patients had negative HBsAg. No difference was observed in the response rate between the two treatment groups (HBeAg-positive and HBeAg-negative patients). Overall, high initial levels of serum AST and ALT predicted a good response. Age and liver biopsy findings were factors predictive of response in HBeAg-positive and HBeAg-negative patients respectively. Sex, epidemiological factors, treatment and type of virus did not correlate with the response to interferon. CONCLUSIONS: A sustained response to interferon alpha was observed in 45% of the patients with chronic hepatitis B. HBeAg seroconversion was found in up to 50% of HBeAg-positive patients. None of the patients had negative HBsAg. Overall, the response rate was higher in patients with high pretreatment serum aminotransferase levels. Age was the predictive factor in HBeAg-positive patients, and histological features were predictive in the HBeAg-negative group. However, further studies in a larger patient population are necessary to obtain well-substantiated conclusions.

Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist.

BACKGROUND/AIM: Ebrotidine is a new H2-receptor antagonist marketed in Spain in early 1997 and withdrawn in July 1998. We report 11 cases of acute liver injury related to ebrotidine and submitted to a Regional Registry of Hepatotoxicity between June 1997 and August 1998. METHODS: In all cases a structured protocol was used to ascertain the role of ebrotidine and to exclude other causes (viral, immunologic, metabolic) of liver injury. RESULTS: All patients showed clinical symptoms of acute hepatitis, with a marked increase in aminotransferase activities (ALT values ranging from 15 to 91 times the upper limit of normal). Total bilirubin values were also greatly increased (mean 16 mg/dl), and the liver injury was defined as hepatocellular. Features of hypersensitivity were absent. Liver biopsy was done in three patients. Histopathological examination revealed mainly centrozonal necrosis (two cases) or massive necrosis (one patient). Withdrawal of the drug was followed by a gradual improvement in liver dysfunction, except in one patient who developed fulminant hepatic failure and died. There was a positive response to rechallenge in one patient after an inadvertent drug administration. CONCLUSION: Ebrotidine therapy seems to be associated with severe acute liver injury, and therefore its benefit/risk ratio is unfavorable. The relative rareness and unpredictability of the injury, the lack of dose-relationship and the absence of hallmarks of drug allergy are suggestive of an idiosyncratic metabolic mechanism.

Response of chronic hepatitis C to interferon-alpha treatment and relationship with iron metabolism.

AIM: to prospectively analyze the influence of iron metabolism of the response to interferon-alpha therapy in chronic hepatitis C. METHODS: ninety-two patients with chronic hepatitis C treated with recombinant alpha-interferon were included. Basal serum levels of iron, ferritin and transferrin saturation were compared in responding and nonresponding patients. Additional epidemiologic, histologic and biochemical variables were studied as predictors of response to interferon-alpha therapy. RESULTS: we studied 57 men (62%) and 35 women (35%) with a mean age of 40 years. Biopsy specimens were classified as having chronic active hepatitis (63%), chronic persistent hepatitis (33.8%) or cirrhosis (3.2%). The basal serum levels of iron and ferritin were significantly higher in non responders (126 +/- 9.1 mu/dL and 222.7 +/- 31.9 eta g/dL respectively; p < 0.05) than in responders (101 +/- 5.7 micrograms/dL and 136 +/- 24.1 eta g/dL). Mean transferrin saturation was also higher in nonresponders (29.7% +/- 2.7% vs 26% +/- 2.02%) although this difference was not significant. Younger age, absence of cirrhosis and parenteral transmission were associated with an improved response to interferon therapy. No relationship was found between the presence of iron in the hepatic parenchyma and response to interferon treatment. CONCLUSIONS: elevated serum levels of iron, ferritin, or both may be associated with a worse response to interferon-alpha therapy.

[Retrospective multicenter study of the efficacy of interferon alpha in chronic hepatitis C]. / Estudio multicéntrico retrospectivo de la eficacia del interfeón alfa en la hepatitis crónica C.

BACKGROUND: Until very recently, interferon (INF) in Spain was authorized in chronic hepatitis C (C-HCV) at a dosis of 3 megaunits (mu) for 6 months. Nonetheless, the rate of maintained complete response is lower than that obtained with more prolonged treatments. The first aim of this study was to retrospectively know the effectiveness of alpha INF in patients treated for 6 or 12 months with a dosis of 3 or 5-6 MU. The second was to analyze the characteristics of the patients who achieved a maintained complete response. PATIENTS AND METHODS: Patients with C-HCV treated in 9 hospitals in Andalucía, Spain who fulfilled the following conditions were retrospectively analyzed: liver biopsy prior to treatment, positive test for anti HCV and a follow up of at least 6 months after alpha INF treatment. A total of 344 patients were studied: 267 treated with alpha INF-2b, 51 with alpha INF-2a and 26 with lymphoblastoid INF. One hundred ninety-five patients were treated for 6 months and 149 for 12 months. RESULTS: Seventy-seven (22%) of the patients presented maintained complete response, 170 (50%) did not respond and 97 (28%) relapsed. On comparing the three types of interferon used over 6 months, no significant differences were observed. Neither were differences found on comparing the dosis of 3 mu versus 5 or 6 mu. On analyzing the treatments of 6 and 12 months, the following was observed, respectively: maintained complete response 15% vs 32%, relapse 29% vs 30% and non responders 57% vs 38% (p < 0.001). Multivariate analysis demonstrated that the patients who responded the best to INF were those who presented the following characteristics: female sex, age under 40 years last, history of transfusion or IVDA, basal GPT level higher than 145 IU/I, GGT less than 55 IU/I, less evolved histologic lesions and duration of treatment over 12 months. CONCLUSIONS: Of the different treatments analyzed with alpha interferon in chronic hepatitis C, the best was found to be that with 3 mu during 12 months.

[Comparison of the indexes of serologic activity with endoscopy in intestinal inflammatory disease]. / Comparación de los índices de actividad serológicos con la endoscopia en la enfermedad inflamatoria intestinal.

The correlation of the most commonly used clinical and serologic parameters in clinical practice were studied with an endoscopic model for inflammatory bowel disease (IBD). Eighty patients diagnosed with IBD with colic involvement (40 patients with ulcerous colitis [UC] and 40 with Crohn's disease [CD]) were prospectively studied. The CDAI was used as a clinical index of activity in the cases of CD and the True-love and Witts index was used in those with UC. The analytical parameters studied were erythrocyte sedimentation rate (ESR), hemoglobin (Hb), platelets (Th), iron (Fe), protein-C-reactive (PCR), albumin (Ab), orosomucoid (Oro), and alpha-1-antitrypsin (AAT). An excellent correlation was found in the UC in both the clinical index and serologic parameters. However, the correlation in CD was poor and only significant with iron and albumin.

[Thyroid dysfunction in patients with chronic hepatitis C pre and post treatment with interferon]. / Disfunción tiroidea en pacientes con hepatitis crónica C pre y post tratamiento con interferón.

OBJECTIVE: The aim of this study was to evaluate the thyroid function and the dysfunction after interferon therapy in patients with chronic hepatitis C. MATERIAL AND METHODS: Between 1988 and 1994, 119 patients with chronic hepatitis C treated with interferon were reviewed 92 patients received interferon alfa for six or twelve months. 27 patients were treated with interferon beta for six months. Before, during and after interferon therapy, free thyroxine, thyroid-stimulating hormone, antimicrosomal antibodies and antithyroglobulin antibodies were measured in 51 patients. None of the patients had abnormal thyroid function or autoimmune disease before treatment. RESULTS: Among the interferon-treated patients, 6% developed biochemical evidence of thyroid dysfunction during or after therapy. Most cases had hypothyroidism. Thyroid dysfunction was statistically more frequent in the female sex, older patients and in patients who received greater total dose of interferon. In one patient the titters of antimicrosomal thyroid antibodies increased from 1/10 to 1/40 and another patient was positive in a dilution of 1/80 by the time of onset of thyroid disease. Thyroid disease (hypothyroidism) developed in (3.5%) of untreated patients with chronic hepatitis C. CONCLUSIONS: Interferon therapy can development autoimmune thyroid fenomena. Thyroid dysfunction and the presence of antithyroid antibodies before therapy can be a contraindication to the use of interferon in these patients. It is important that patients undergoing interferon therapy be tested for antithyroid antibodies and thyroid function before treatment and be monitored during the course of therapy. Also, it is important to evaluate the factors related with the development of thyroid dysfunction (age, sex, interferon dose...).

[Laparoscopic diagnosis of hepatic angiomas after erroneous imaging techniques]. / Diagnóstico laparoscópico de angiomas hepáticos tras error por técnicas de imagen.

Hemangiomas are de most frequent benign liver tumours. Their clinical relevance is small but they can cause to the patient and/or the physician a great worry because can be indistinguishable from hepatic malignances. From 1991 to 1994 five patients with liver hemangiomas were diagnosed by laparoscopy after a erroneous and/or contradictory interpretation by various imaging techniques. In four cases hemangiomas resembled metastatic carcinoma of the liver, and in the other patient hemangioma was interpreted as focal nodular hyperplasia. Diagnosis and treatment are discussed.

Intraepithelial and lamina propria leucocyte subsets in inflammatory bowel disease: an immunohistochemical study of colon and rectal biopsy specimens.

AIMS: To gain new insights into the pathogenesis and differential diagnosis of ulcerative colitis and colonic Crohn's disease. METHODS: Immunohistochemistry for different leucocyte subsets was performed in biopsy specimens of the sigmoid colon and rectum from 55 patients with inflammatory bowel disease and 11 healthy controls. RESULTS: Colonic biopsy specimens from patients with active ulcerative colitis had significantly higher numbers of CD45+ and CD3+ leucocytes compared with those from patients with inactive disease, and higher numbers of total leucocytes and macrophages than those from patients with Crohn's disease. Rectal biopsy specimens from patients with Crohn's disease had greater numbers of intraepithelial leucocytes (CD45, CD3 and CD8 cells) than specimens from patients with active or inactive ulcerative colitis, or from healthy controls. CONCLUSIONS: Because of the phenotypic differences in the inflammatory infiltrate in the mucosa from the sigmoid colon and the rectum, the segment of the intestine to be biopsied should be specified. Assessment of the leucocytic component of the intraepithelial infiltrate in rectal biopsy specimens was more useful than examination of colonic biopsy specimens in the differential diagnosis of ulcerative colitis and Crohn's disease.

[Emergency laparoscopy. A 20-year experience]. / Laparoscopia de urgencia. Experiencia de 20 años.

We revised 7988 laparoscopies over twenty years. Three hundred and ninety three were urgent laparoscopies: 325 patients with acute spontaneous abdomen and 68 acute traumatic abdomen. Emergency laparoscopy is made in patients with, both spontaneous and traumatic acute abdomen, when diagnosis is not made in 8 hours with the usual clinical and imaging methods. Acute diffuse peritonitis was the commonest finding in the first group (21%) and splenic rupture in the traumatic group (34%). There were two severe complications (0.5%): pulmonary oedema in a patient with myocardial disease and a respiratory failure in a old patient, which were resolved. We had two deaths related to laparoscopic diagnosis: massive mesenteric thrombosis and fecal peritonitis. There are few contraindications and tolerance is very good. This study shows a sensitivity of 98%, a specificity of 90%, a predictive positive value greater than 98% and a negative predictive value of 100%. In summary, the present study demonstrates that emergency laparoscopy is a effective diagnostic method in acute abdominal pain of uncertain aetiology.