Efficacy and safety of administering oral misoprostol by titration compared to vaginal misoprostol and dinoprostone for cervical ripening and induction of labour: study protocol for a randomised clinical trial.

BACKGROUND: Among the various methods available, the administration of prostaglandins is the most effective for inducing labour in women with an unfavourable cervix. Recent studies have compared treatment with various titrated doses of oral misoprostol with vaginal misoprostol or dinoprostone, indicating that the use of an escalating dose of an oral misoprostol solution is associated with a lower rate of caesarean sections and a better safety profile. The objective of this study is to assess which of these three therapeutic options (oral or vaginal misoprostol or vaginal dinoprostone) achieves the highest rate of vaginal delivery within the first 24 h of drug administration. METHODS: An open-label randomised controlled trial will be conducted in Araba University Hospital (Spain). Women at ≥41 weeks of pregnancy requiring elective induction of labour who meet the selection criteria will be randomly allocated to one of three groups: 1) vaginal dinoprostone (delivered via a controlled-release vaginal insert containing 10 mg of dinoprostone, for up to 24 h); 2) vaginal misoprostol (25 µg of vaginal misoprostol every 4 h up to a maximum of 24 h); and 3) oral misoprostol (titrated doses of 20 to 60 µg of misoprostol following a 3 h on + 1 h off regimen up to a maximum of 24 h). Both intention-to-treat analysis and per-protocol analysis will be performed. DISCUSSION: The proposed study seeks to gather evidence on which of these three therapeutic options achieves the highest rate of vaginal delivery with the best safety profile, to enable obstetricians to use the most effective and safe option for their patients. TRIAL REGISTRATION: NCT02902653 Available at: https://clinicaltrials.gov/show/NCT02902653 (7th September 2016).

Linking hearing impairment, employment and education.

OBJECTIVE: To analyse the impact that hearing impairment and other relevant variables have on the education and employment situation of those affected by it in the Principality of Asturias, Spain. METHODS: To achieve this objective, two discrete choice models (probit) are presented. The first one associates, among other variables, hearing impairment with the individual's employment status and in the second model, an ordered multinomial probit model is used to analyse, among other variables, how the impairment affects the individual's level of studies. RESULTS: Although the levels of statistical significance are low, the model's estimates appear to indicate that hearing impairment in Spain increases the probability of being unemployed by 18.4% (P = 0.09). Additionally, the people suffering from such a disability are, compared with the rest of the population, 10.2% (P = 0.05) more likely to have only completed elementary studies without pursuing any further education. CONCLUSIONS: If an individual is able to reach a level of secondary or higher education thus enabling a future incorporation to the work place, a benefit is obviously generated for both the individual as well as society (which has additionally incurred an investment in human capital). In this regard, encouraging the education of hearing-impaired students would profit both the individual (who receives an early integration as a child), which may contribute positively to family and social factors, as well as society who have incurred the investment. Therefore, our result could indicate that programmes created to support individuals with this type of disability represent an increase of welfare both individually and socially.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Intestinal perforation after pediatric liver transplantation: risk factors and management. / Perforación intestinal tras trasplante hepático pediátrico: factores de riesgo y manejo.

BACKGROUND: Intestinal perforation (IP) after pediatric liver transplant (PLT) is an uncommon complication with high mortality reported. The aim of this study is to identify the risk factors and management of this complication. MATERIALS AND METHODS: Retrospective study of IP after PLT from January 2014 to October 2020. RESULTS: Four intestinal perforations were indentificated in 102 PLT (3,9%). Three patients with BA and one neonate with hemochromatosis (HC) presented this complication. The mean weight of patients with IP was 6.3± 2.5kg (3.1-9) and 19.9 ± 15.4kg for the rest (p< 0.05). All IP with BA had a previous laparotomy. Two living donors and two left lateral reduced liver were implanted. The diagnosis of intestinal perforation was done on day 11 ± 3.3 (8-15 days). Diagnosis was suspected with clinical and biological signs of perforation, CT scan confirmed the diagnosis in patiens with BA and by direct visualization through the mesh for temporary closure in the patient with hemocromatosis. Urgent laparotomy was performed. We identified three colonic perforations, all of them in BA patients and all repaired with direct suture. The patient with HC presented multiple perforations secondary to necrotizing enterocolitis requiring an ileostomy and finally died due to multiorgan failure. CONCLUSION: Intestinal perforation after PLT is an infrequent complication. Age, weight, previous laparotomy and BA could be risk factors for IP in PLT. Urgent laparotomy after diagnosis should be performed in order to reduce mortality. Isolated IP with adequate treatment might not affect long term outcomes after pediatric liver transplantation.

INTRODUCCION: La perforación intestinal (PI) tras trasplante hepático pediátrico (THP) es una complicación poco frecuente, pero con una elevada mortalidad. El objetivo de este estudio es identificar los factores de riesgo y el manejo de esta complicación. MATERIAL Y METODOS: Estudio retrospectivo de la PI tras THP entre enero de 2014 y octubre de 2020. RESULTADOS: Se hallaron 4 perforaciones intestinales en 102 THP (3,9%). Presentaron esta complicación 3 pacientes con atresia biliar (AB) y un neonato con hemocromatosis (HC). El peso medio de los pacientes con PI era de 6,3 ± 2,5 kg (3.1-9) y de 19,9 ± 15,4 kg en el caso del resto (p<0,05). Todos los pacientes con PI y AB habían sido sometidos previamente a laparotomía. Se implantaron 2 hígados de donantes vivos y 2 hígados laterales reducidos izquierdos. El diagnóstico de perforación intestinal se efectúo en el día 11 ± 3,3 (8-15 días), sospechándose con signos clínicos y biológicos de perforación, y confirmándose mediante escáner en los pacientes con AB y mediante visualización directa a través de la malla para el cierre temporal en el paciente con hemocromatosis. Se llevó a cabo laparotomía de urgencia. Se identificaron 3 perforaciones de colon, todas ellas en pacientes con AB y reparadas con sutura directa. El paciente con HC presentaba múltiples perforaciones secundarias a enterocolitis necrotizante que precisaron ileostomía, falleciendo finalmente como consecuencia de un fallo multiorgánico. CONCLUSIONES: La perforación intestinal tras THP es una complicación poco frecuente. La edad, el peso, las laparotomías previas y la AB podrían ser factores de riesgo de PI en el THP. Para reducir la mortalidad, es conveniente practicar una laparotomía de urgencia tras el diagnóstico. Una PI aislada con un adecuado tratamiento puede no influir en los resultados a largo plazo tras un trasplante hepático pediátrico.

Obesity as an adipose tissue dysfunction disease and a risk factor for infections - Covid-19 as a case study.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) disease (COVID-19) is a novel threat that hampers life expectancy especially in obese individuals. Though this association is clinically relevant, the underlying mechanisms are not fully elucidated. SARS CoV2 enters host cells via the Angiotensin Converting Enzyme 2 receptor, that is also expressed in adipose tissue. Moreover, adipose tissue is also a source of many proinflammatory mediators and adipokines that might enhance the characteristic COVID-19 cytokine storm due to a chronic low-grade inflammatory preconditioning. Further obesity-dependent thoracic mechanical constraints may also incise negatively into the prognosis of obese subjects with COVID-19. This review summarizes the current body of knowledge on the obesity-dependent circumstances triggering an increased risk for COVID-19 severity, and their clinical relevance.

Applicability and results of liver transplant combined with neoadjuvant chemo-radiotherapy in the treatment of unresectable hilar cholangiocarcinoma. / Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable.

BACKGROUND: In 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AIM: To analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. METHODS: Observational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. RESULTS: Between 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. CONCLUSION: The suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

No-touch hepatic hilum technique to treat early portal vein thrombosis after pediatric liver transplantation.

A 'no-touch' hilum technique used to treat early portal vein complications post-liver transplantation in five children with body weight <10 kg is described. Four patients developed thrombosis and one portal flow absence secondary to collateral steal flow. A vascular sheath was placed through the previous laparotomy in the ileocolic vein (n = 2), inferior mesenteric vein (n = 1) or graft umbilical vein (n = 1). Portal clots were mechanically fragmented with balloon angioplasty. In addition, coil embolization of competitive collaterals (n = 3) and stent placement (n = 1) were performed. The catheter was left in place and exteriorized through the wound (n = 2) or a different transabdominal wall puncture (n = 3). A continuous transcatheter perfusion of heparin was subsequently administered. One patient developed recurrent thrombosis 24 h later which was resolved with the same technique. Catheters were removed surgically after a mean of 10.6 days. All patients presented portal vein patency at the end of follow-up. Three patients are alive after 5 months, 1.5 and 3.5 years, respectively; one patient required retransplantation 18 days postprocedure and the remaining patient died of adenovirus infection 2 months postprocedure. In conclusion, treatment of early portal vein complications following pediatric liver transplantation with this novel technique is feasible and effective.

Factors Related to Non-participation in the Basque Country Colorectal Cancer Screening Programme.

Background: Despite the high participation rates in the Basque Country, colorectal cancer screening programme (Spain), there is still a part of the population that has never participated. Since it is essential to ensure equal access to health services, it is necessary to identify the determinants of health and socio-economic factors related to non-participation in the screening programme. Methods: Cross sectional descriptive study including all invited population in a complete round between 2015 and the first trimester of 2017. Health risk factors available in medical records and their control have been analyzed using univariate and multivariate analyses. Results: 515,388 people were invited at the programme with a 71.9% of fecal immunochemical test participation rate. Factors that increase the risk of non-participation are: being men (OR = 1.10, 95% CI 1.09-1.12); younger than 60 (OR = 1.18, 95% CI 1.17-1.20); smoker (OR = 1.20, 95% CI 1.18-1.22); hypertensive (OR = 1.14, 95% CI 1.12-1.15) and diabetic (OR = 1.40, 95% CI 1.36-1.43); having severe comorbidity (OR = 2.09, 95% CI 2.00-2.19) and very high deprivation (OR = 1.15, 95% CI 1.12-1.17), as well as making <6 appointments to Primary Care in 3 years (OR = 2.39, 95% CI 2.33-2.45). Still, the area under the curve (AUC) indicates that there are more factors related to non-participation. Conclusions: The participation in the Basque Country colorectal cancer-screening Programme is related to some risk factors controlled by Primary Care among others. Therefore, the involvement of these professionals could improve, not only the adherence to the CRC screening, but also other health styles and preventive interventions.

Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin with rapamycin plus tacrolimus in liver transplant patient.

OBJECTIVE: To report a severe interaction between simvastatin and rapamycin resulting in rhabdomyolysis and acute renal failure in a liver transplant patient. BACKGROUND: A 56-year-old man with hepatitis C virus cirrhosis (Child B) was diagnosed with hepatocellular carcinoma and underwent liver transplantation in April 2007. He was immunosuppressed with tacrolimus (FK) and mycophenolate mofetil (MMF). Postoperative complications were arterial hypertension and renal insufficiency. In June 2007, liver dysfunction was detected and acute rejection was diagnosed by biopsy. He received three 500-mg boluses of methylprednisolone and FK levels were maintained between 10 and 12 ng/mL. Laboratory values revealed persistent rejection and MMF was stopped with initiation of rapamicin. One month later, hyperlipidemia appeared as a consequence of rapamicin therapy; simvastatin was administered. In August 2007, the patient was readmitted due to severe muscule pain and the inability to ambulate. Laboratory values were: total bilirubin 16 mg/dL, serum creatinine 4.3 mg/dL, and total creatine kinase (CK) 42,124 U/L. With the suspicion of rhabdomyolysis, leading to worsening of his basal renal insufficiency, rapamycin and tacrolimus were stopped. Hemodialysis was initiated owing to renal failure and hyperkalemia. Some hours later, the patient developed ventricular fibrillation and respiratory failure and succumbed. DISCUSSION: Calcineurin inhibitors (CNI), corticosteroids, and mammalian target of rapamycin (m-TOR) inhibitors are associated with adverse dyslipidemic effects. To reduce the overall cardiovascular risk in these patients, lipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been widely used. CNI and m-TOR inhibitors, as well as most statins, are metabolized by cytochrome P450 (CYP)3A4; thus, pharmacokinetic interactions between these drugs are possible. Previous reports have indicated an increased risk of rhabdomyolysis in the presence of concomitant drugs that inhibit simvastatin metabolism. CONCLUSIONS: Concomitant administration of statin therapy and drugs that inhibit cytochrome P450 (CYP)3A4 increased the risk of rhabdomyolysis in a patient suffering liver and renal dysfunction.

Non-anatomical intestinal transplantation.

INTRODUCTION: Intestinal transplantation is the only long-range treatment option for patients with intestinal failure. We report an exceptional case of isolated intestinal transplantation with the implant in a non-anatomical position. CLINICAL CASE: The patient was a thirty-eight-year-old man (60 kg weight, 180 cm height, 18.3 body mass index) with intestinal failure and home parenteral nutrition due to a short-bowel syndrome for which intestinal transplantation was indicated. The patient had a vascular malformation with the cava vein located left to the aorta, and the intestine was implanted with a 180 masculine rotation around the mesenteric axis, so that the implant s superior mesenteric artery and vein matched the recipient s cava and aorta. Postoperative follow-up was excellent and the patient was discharged after six weeks with a 10-kg gain in body weight. DISCUSSION: This non-anatomical intestinal implantation of the small bowel, previously unreported, offers technical advantages over other options. Adequate intestinal function represents a unique model to prove the viability of intestinal implants in a non-anatomical position.

"Non-Touch" Vena Cava Technique as an Improvement in Combined Lung and Liver Procurement in Controlled Donation After Circulatory Death.

The number of organs retrieved from donation after circulatory death (DCD) donors has continued to rise in recent years. The functional superiority of DCD organs is achieved when the lungs are perfused with cold perfusion and livers with normothermic regional perfusion (NRP). Thus, a precise surgical technique is required to combine thoracic and abdominal organ procurement. The technique used at our center consists of a rapid laparotomy and middle sternotomy, then the abdominal aorta (Ao) and abdominal inferior vena cava (VC) are cannulated and the descending thoracic Ao is cross-clamped. NRP is started at that point. As a variation of previously described techniques, the thoracic vena cava is not initially clamped in order to improve the return of blood volume to the NRP circuit. The pulmonary artery is cannulated to flush the lungs and the left atrial appendage is opened for drainage. After 120 minutes, NRP perfusion is stopped and the organs are flushed with cold preservation solution. In 2016, 3 livers and 6 lungs were harvested at our center using the technique described. After a minimum follow-up of 1 year, no evidence of biliary complications was observed. The combined procurement of lungs after room temperature perfusion and liver after NRP without initial clamping of the thoracic VC is feasible, with excellent function post-transplantation.

Acquired neuromuscular dysfunction in the intensive care unit. / Disfunción neuromuscular adquirida en la unidad de cuidados intensivos.

INTRODUCTION: Polyneuropathy and myopathy, grouped under the term «intensive care unit-acquired weakness¼ (ICUAW), are neuromuscular pathologies to which patients in the intensive care unit (ICU) are susceptible. They are multifactorial pathologies, prolonged connection to a ventilator is one of the most common. The objective of this review was to identify the efficacy of different rehabilitative treatments in patients with ICUAW, and the relationship between ICUAW and a series of indicators. METHODS: A systematic review of the primary studies selected from the Medline, Scielo, Web of Science, Cochrane, Cuiden and Science Direct databases was carried out, following the guidelines of the PRISMA statement, by which the search protocol was established. RESULTS AND CONCLUSIONS: Of 161 articles, only 10 were selected to be part of this review, in which a total of 717 patients admitted to the ICU were studied. A statistically significant relationship was observed between ICUAW and failure in ventilator disconnection, mortality, increase in ICU stay and the time that the patients required mechanical ventilation. Moreover, all this improved in this type of patients with the application of a rehabilitation therapy. The use of corticosteroids, was not shown to be related to neuromuscular alteration.

Portocaval shunt throughout anhepatic phase in orthotopic liver transplantation for cirrhotic patients.

The aim of this study was to assess whether the use of a temporary portocaval shunt (PCS) with inferior vena caval (IVC) preservation during orthotopic liver transplant procedures (OLT) in cirrhotic patients had any advantage. This work evaluated a group of cirrhotic patients who underwent liver-transplant between 1999 and 2006 with a temporary portocaval anastomosis and IVC preservation (PC group, n = 356) versus an historical group (no-PC group, n = 45) with only IVC preservation. We excluded cases of fulminant hepatitis, retransplants, portal vein thrombosis, or prior surgical portosystemic shunts. In both groups, graft reperfusion was achieved by simultaneous arterial and venous revascularization. Donor, recipient, and surgical characteristics were similar in both groups. The PCS group displayed significantly higher portovenous flow (PVF) than the no-PCS group (773 +/- 402 mL/min vs 555 +/- 379 mL/min, P = .004). We studied two subgroups: high PVF subgroup A (>800 mL/min; mean 1099 +/- 261 mL/min) and a low PVF subgroup B (<800 mL/min; mean 433 +/- 423 mL/min). In the high flow group (subgroup A) with PCS, a smaller number of blood units were required and better renal function was exhibited at the third postoperatory day. In contrast, no differences were observed among subgroup B between patients with or without PCS. The use of PCS with IVC preservation during the OLT enhanced the hemodynamic recipient status requiring a smaller number of blood units and displaying better renal function.

Liver transplantation in childhood with more than 10 years of follow-up: analysis of a single-center experience.

UNLABELLED: We pioneered pediatric liver transplantation (OLT) in Spain (June 1985). The aim of this study was to evaluate the current status of our OLT recipients with more than 10 years follow-up. MATERIALS AND METHODS: The 50 patients with >10 years follow-up had a mean age at OLT of 5.6 years with 60% showing a main indication of biliary atresia. All but one (tacrolimus) received cyclosporine. RESULTS: No patient loss occurred among these patients. Eighteen patients had follow-up >15 years and 12 >20 years. The incidence of acute rejection was 56%; chronic rejection, 16%; and lymphoproliferative disorders, 12%. Seven (14%) required retransplantation at a mean of 4.2 years after the first OLT due in four instances to chronic rejection. After 10 years of follow-up, one patient developed portal vein thrombosis and three biliary strictures. All patients remain on immunosuppression. In 64% cyclosporine was switched to tacrolimus or another agent. One patient developed acute rejection at 19.2 years. In 14% of patients the liver function test is abnormal with serum creatinine is >1.5 mg/dL in 10%; one requires insulin and three, antihypertensive drugs. Noncompliance with medications was detected in 10%. Three recipients had offspring. CONCLUSIONS: OLT was an effective treatment with a good quality of life also on long-term follow-up.

Recurrence of hepatocellular carcinoma after liver transplantation.

Outcome after liver transplantation (OLT) clearly depends on recurrence of hepatocellular carcinoma (HCC). After recurrence, patient outcome will depend on the time and site of appearance. The aim of this study was to analyze the therapeutic implications of tumor recurrence behavior. From October 1988 to December 2005, 685 patients received OLT, including 202 due to HCC (32%). We analyzed 28 recurrences (15.2%) among 184 patients who survived at least 3 months (minimum follow-up 1 year). According to the time of recurrence, we divided the patients into early recurrence (ER < 12 months; n = 9; 32.1%) and late recurrence (LR > 12 months n = 19; 67.9%). Actuarial survivals at 1, 5, and 10 years were 82%, 65%, and 50% and disease-free survival, 80%, 58%, and 46%, respectively. Risk factors for recurrence were: vascular invasion (P < .01), bad differentiation (P < .01), and previous hepatectomy (P < .05). After OLT, ER presented at: 5.7 +/- 2.3 months (range 3-10) vs 33.5 +/- 24.3 months (range 12-103) for LR P < .001). Survival postrecurrence (SPR) was shorter: 3.1 +/- 2.4 (range 1-8) months vs 16.4 +/- 14.2 (range 1-5) months (P < .001). Treatment was offered to one ER (11%) and to eight LR (47.1%; P < .05), achieving in these cases longer SPR: 20.1 +/- 14 vs 6.9 +/- 9 months (P < .05). The most common sites of recurrence were liver (n = 7), lung (n = 7), bone (n = 5), adrenal gland (n = 2), peritoneum (n = 2), lymph node (n = 2), skin (n = 2) or cerebral (n = 1). Early recurrences showed short survivals; no treatment could be offered to these patients. Liver recurrence appeared early. In contrast, most lung recurrences appeared later with the possibility of treatment and longer SPR. Bone recurrence appeared later, usually associated with other locations. Treatment was palliative and prognosis was worse. Skin and lymph node recurrences can be treated curatively with prolonged survival. In conclusion, HCC recurrence was difficult to treat curatively and was only prevented by employing restricted criteria.

Gastrointestinal complications in liver transplant recipients: MITOS study.

INTRODUCTION: Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. OBJECTIVE: The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. PATIENTS AND METHODS: This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. RESULTS: The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. CONCLUSIONS: The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

[Peripheral cholangiocarcinoma: results of surgical treatment]. / Colangiocarcinoma periférico: resultados del tratamiento quirúrgico.

INTRODUCTION: Peripheral cholangiocarcinoma (PC) is an uncommon primary hepatic tumor that represents 10% of hepatic resections for primary malignant tumors in our experience. PATIENTS AND METHODS: From 1988 to 2004, 29 patients with a diagnosis of PC were treated in our unit. One patient was treated with chemoembolization and the remainder underwent surgery. In 7 patients, hepatectomy was not performed due to the presence of an extrahepatic tumor or massive hepatic invasion. The resectability index was 75%. Twenty-one patients underwent radical excision of PC and comprised the study group. RESULTS: The mean age was 60 years with a slight predominance of women. Sixty-two patients were symptomatic and tumoral markers were elevated in 58%. PC developed in normal liver in 15 patients, in cirrhotic liver in 2 patients and in the context of chronic hepatitis in 4 patients. The mean tumoral size was 7 cm (between 1.6 and 13 cm). Multiple tumors were found in 3 patients, invasion of the hepatic hilum lymph nodes was found in 8 patients and vascular invasion was observed in a further 8 patients. Major hepatectomy was performed in 90% of the patients; radical lymphadenectomy of the hepatic hilum was performed in 15 patients and excision of the extrahepatic biliary tract followed by Roux-en-Y hepaticojejunostomy in 4 patients. Operative mortality occurred in 3 patients (14%); one cirrhotic patient died 4 days after surgery from cardiovascular causes and 2 patients died from liver failure after extensive hepatectomies that included resection of the inferior vena cava and suprahepatic veins. Complications occurred in 33% of the patients. Ten patients (47%) died. Of these, 6 died from tumoral recurrence. Tumoral recurrence occurred in 9 patients (5 hepatic and 4 extrahepatic). Hepatic recurrences were treated with radiofrequency ablation in 2 patients and chemotherapy in 5 patients. The median survival was 11 months. Actuarial survival at 1, 3 and 5 years was 60%, 47% and 47% respectively. Disease-free survival at 1, 3 and 5 years was 50%, 31% and 31% respectively. In univariate analysis, significant risk factors for mortality were lymphatic invasion and a resection margin of less than 1 cm. In multivariate analysis, negative factors for tumoral recurrence were lymphatic invasion, satellitosis, and poor tumoral delimitation. CONCLUSION: Surgical treatment of PC through radical hepatic resection with margins of more than 1 cm in patients without nodal invasion provides good results with a 5-year survival of 79%.

[Giant trichoblastoma]. / Tricoblastoma gigante.

Trichoblastoma is a benign tumour that differentiates towards the hair germ epithelium with a dense fibrous stroma that gives a hair bulb-like appearance. Currently it is being used the classification proposed by Ackerman and colleagues. The lesion usually presents as a solitary nodule, 1-2 cm in diameter, more frequently located on the scalp and face, that is easily removed during surgery. We describe the case of a large trichoblastoma located on the buttock.

Safety and Efficacy of Early Everolimus When Calcineurin Inhibitors Are Not Recommended in Orthotopic Liver Transplantation.

Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2. In 23 patients, immunosuppression was EVL + mycophenolate mofetil/mycophenolate sodium + steroids, and EVL + tacrolimus + steroids/mycophenolate sodium was used in 4 cases. Neurotoxicity disappeared in all patients. Renal function in patients with renal impairment improved from a median of 32 mL/min/1.73 m2 at the moment of implementation of EVL to 62 mL/min/1.73 m2 at 1 year. Four patients (14.3%) developed acute cellular rejection. We observed incisional hernia in 4 patients (14.3%), hematologic complications in 6 (21.4%), proteinuria in 2 (7.1%), edema and/or effusions in 8 (28.6%), and dyslipidemia in 12 (42.8%). No arterial complications were observed. EVL was withdrawn in 5 patients during the 1st year after LT. One-year patient survival was 92.7%. In conclusion, use of EVL within the 1st month after LT when calcineurin inhibitors are not recommended seems to be an effective therapeutic option with an acceptable safety profile.

Analysis of discarded livers for transplantation.

The aims were to study the causes of nonacceptance of a liver for transplantation after exploration by the donor surgical team and to compare donor characteristics of transplanted and discarded livers. All donor harvesting procedures performed by our unit from 1988 to 2004 were retrospectively studied. Donors were divided in those accepted and transplanted and those discarded by the donor surgical team. The causes of rejection were classified as hepatic and nonhepatic. Donor characteristics of accepted, transplanted livers were compared with those rejected for hepatic reasons. Seven hundred fifty four donor liver procurements were performed: 628 livers were accepted and transplanted (TL), 126 (17.5%) were discarded owing to extrahepatic (n = 16) or hepatic causes (n = 110). Extrahepatic causes were: technical (5.6%), and incidental tumors infection (7.2%). Hepatic causes were: chronic disease or cirrhosis (26.4%), ischemic or septic liver (16.8%), and steatosis (44%). Univariate analysis of donor characteristics showed a significant difference in older age, diabetes, alcohol intake, arterial hypertension, abnormal liver ultrasound (US) exam, and abnormal liver function tests in the group of discarded livers. Obesity and the finding of steatosis in US exam were the only two factors that maintained statistical significance upon multivariate analysis.