Breakthrough rhinocerebral mucormycosis in a liver transplant patient receiving caspofungin.

Zygomycetes are among the most frequent causes of non-Aspergillus mycelial fungal infections in transplant recipients. We have described a single case of breakthrough zygomycosis. A young Japanese woman presented because of idiopathic fulminant hepatitis and renal failure. On the third day of admission, she underwent orthotopic liver transplantation. A considerable amount of red blood cells and fresh frozen plasma were transfused during surgery. On posttransplant day 2, Candida albicans was isolated from respiratory secretions; prophylactic caspofungin was prescribed. During the next 6 days, C albicans was isolated from tracheal secretions, surgical wound, and exudates and stools. Ventilator-associated pneumonia was diagnosed day 4. Her renal function did not improve during the postoperative period; the patient continued on hemodialysis. On day 28, a dark blue eschar due to zygomycosis was detected on the skin of the nose. Tracheal and nasal exudates yielded Rhizopus sp. The patient died 12 hours later due to multiorgan failure with hypothermia. The fatal evolution in this case may be related to a presumed brain infarction after progressive vessel fungal invasion. The presented case had 2 risk factors related to zygomycosis. A high index of suspicion is required in transplant recipients with risk factors for zygomycosis. Early diagnosis and surgery with appropriate systemic fungal drugs (amphotericin B) are mandatory to improve the prognosis.

Tumor intraabdominal desmoplásico de células pequeñas y redondas. Revisión de la literatura a propósito de un caso con estudio citológico, histopatológico, inmunohistoquímico y molecular / No disponible

Propósito: Revisar los hallazgos citohistopatológicos,inmunohistoquímicos y moleculares del tumorde células pequeñas redondas (DSRCT).Material y métodos: Varón de 18 años conmasa intraabdominal epigástrica.Resultados: Tumoración constituida por unaproliferación en nidos y difusa de células pequeñasindiferenciadas sobre estroma desmoplásico, conformación de rosetas, inmunorreactivas para citoqueratinas,vimentina, desmina y enolasa y la fracciónWT1 de la proteína EWS/WT1. El estudio moleculardemostró la traslocación t(11;22)(p13;q12).Conclusiones: La formación de rosetas y lasáreas sólidas han sido descritas en otros casos deDSRCT. El producto quimérico puede detectarse medianteRT-PCR, Southern-blot, Western-blot e inmunohistoquímica.El estudio citológico está especialmenteindicado en el diagnóstico de recidivas. Eldiagnóstico diferencial debe incluir el grupo de tumoresindiferenciados de células pequeñas y redondas

Purpose: To review the cyto-histopathological, immunohistochemical and molecular characteristicsof small round cell desmoplastic tumor (DSRCT).Material and methods: A 18 year old malewith an intraabdominal epigastric mass.Results: The tumor consisted of nests andmasses of undifferentiated small round cellsembedded in a desmoplastic stroma, with areas ofrosette formation immuno-reactive to cytokeratins,vimentin, desmin, enolase, and WT1 fraction of theEWS/WT1 fusion protein transcript. The molecularstudy demonstrated the existence of the translocationt(11;22)(p13;q12).Conclusions: The solid areas and rosetteformation have been described in other cases ofDSRCT. The chimeric transcription product can bedetected by RT-PCR, Southern-blot, Western-blot,and immunohistochemistry. Cytology is especiallyuseful in recurrences. The differential diagnosisshould be made with the small round undifferented cell tumors group (AU)

Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation.

The objective of the study was to assess the efficacy of antiviral therapy in patients with hepatitis C virus (HCV) recurrence after liver transplantation (OLT). We included 30 patients of mean age 56 years, who experienced HCV recurrence after OLT. Mean time from OLT to the beginning of therapy was 57 months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21), cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously been diagnosed with allograft HCV cirrhosis. Patients were treated with peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48 (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20 months, two patients had died due to biliary sepsis (while on therapy) and acute myocardial infarction (7 months after the end of therapy). End of treatment virological response was achieved in 19 patients (63.3%) and sustained virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P = .732). Every patient had some adverse event; in 11 patients (36.7%) it was withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the starting dose was decreased (40%). There were neither rejection episodes nor cirrhotic complications during therapy, but infections were more common in cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients the sustained virological response to combined antiviral therapy was similar to that in noncirrhotic patients, but severe adverse events including infections were much more common.

Therapy of intractable pruritus with MARS.

INTRODUCTION: Pruritus is the most disabling symptom in patients with cholestatic liver diseases. Many drug therapies have been used for the treatment of these diseases, with different outcomes. The molecular adsorbent recirculating system (MARS) has been used in the treatment of intractable pruritus in cholestatic syndromes. We report our experience with MARS in 3 patients with intractable pruritus on the waiting list: 2 liver transplant recipients and a patient with primary biliary cirrhosis. PATIENTS AND RESULTS: Two middle-aged women and 1 middle-aged man, who were recipients of an orthotopic liver transplant for primary biliary cirrhosis, underwent three (n = 2) and two (n = 1) 6-hour sessions of MARS due to medically uncontrollable pruritus. All noted marked improvement of pruritus, with decreased bilirubin levels, but this improvement lasted only a few days in all cases. We observed no changes in transaminase or albumin levels, or prothrombin time. Complications included an episode of angina due to anemia caused by jugular catheter bleeding, and thrombocytopenia in all patients. CONCLUSIONS: MARS is an effective treatment for intractable pruritus in cholestatic liver diseases, although its beneficial effect is short. This extracorporeal liver device is safe, because most related adverse events are mild.

Effectiveness of pegylated interferon and ribavirin in patients with liver HCV cirrhosis.

Clearance of HCV before transplantation could avoid recurrence of hepatitis C in the liver allograft, thereby improving graft and patient survival. We report our experience with combined therapy for patients with HCV cirrhosis, including 12 patients with biopsy-proven liver cirrhosis (n = 7) or previous cirrhotic complications (n = 5). The Child-Pugh score was A in eight patients and B in four. Two patients had hepatocellular carcinoma. Genotype distribution was 1a (n = 2), 1b (n = 8) or 3 (n = 1). Patients received peginterferon alpha2b (1.5 microg/kg once weekly) and ribavirin (10.6 g/kg per day) for 48 weeks (genotype 1) or 24 weeks (genotype 3). Twenty-one months after beginning therapy all the patients remained alive; three have undergone liver transplantation. In one patient treatment was discontinued after 2 months due to cachexia. End-of-treatment virologic response was achieved in five patients (41.7%) and sustained virologic response in three patients (25%). Patients who cleared the virus had negative PCR 4 weeks after beginning therapy. All patients had adverse events. The most common clinical events were asthenia, weight loss, fever, and anorexia. Infectious complications resolved in three patients (25%). Hematologic events were common. Seven of 11 patients (63.6%) who completed therapy required dose reduction. We conclude that therapy with peginterferon and ribavirin in patients with HCV cirrhosis has a similar effectiveness to previous treatments. A virologic response 1 month after the beginning of therapy could be a main predictor of a sustained response.

Efficacy of hepatocellular carcinoma locoregional therapies on patients waiting for liver transplantation.

The aim of this study was to evaluate the efficacy of different locoregional therapies in patients with HCC on the waiting list for liver transplantation. From October 2001 to July 2003, 13 patients, all men, with HCC diagnosed by cytology, were transplanted at our center. Locoregional therapies were percutaneous ethanol injection (PEI), transcatheter hepatic arterial chemoembolization (TACE), and radiofrequency microwave ablation (RFA). PEI was employed in seven patients, TACE in five (one of them associated with PEI) and RFA in one. Efficacy was evaluated by determining the percentage of tumoral necrosis in the liver explant. Five tumors were T4, four T3, three T2, and one T1. Ten were well differentiated, two moderately differentiated, and one undifferentiated. One patient died due to primary graft malfunction. After a median posttransplant follow-up of 15 months, 12 patients are alive with no sign of tumor recurrence. Most patients with solitary nodules <4 cm who received PEI had 90% to 100% tumor necrosis. Larger tumors had 25% to 30% necrosis. TACE was employed in six patients with large and/or multiple tumors, obtaining 20% to 50% tumor necrosis. RFA was employed in one case obtaining 85% necrosis (tumor of 4 cm). No serious complications occurred with any technique. According to our experience, PEI and RFA are effective locoregional therapies to treat hepatocellular carcinomas of <4 cm in patients on the waiting list. For larger tumors, their association with other techniques, such as TACE, seems adequate.

Prevalence of hepatitis C virus genotypes in a Spanish liver transplant unit.

INTRODUCTION: Among the at least six major identified genotypes of HCV, genotype 1b, the one associated with a poorer prognosis, is the most prevalent in Spain. We aimed to compare the distribution of hepatitis C virus genotypes in our liver transplant unit with that of the other HCV patients at our institution (n = 413) in order to assess whether genotype 1b is more prevalent among patients with more severe liver disease. PATIENTS AND METHODS: One hundred eight patients of mean age 56 years included 81 (75%) OLT recipients and 27 (25%) with HCV cirrhosis. Determination of HCV genotypes was made with the Inno-LiPA HCV III. RESULTS: The overall distribution of genotypes was: 1b, 93 patients (86.1%); 1a; eight patients (7.4%); 3, four patients (3.7%); 4; two patients (1.9%), and 2; one patient (0.9%). The distribution was similar among patients with cirrhosis and OLT. Genotype 1b patients were older. Eleven (78.6%) of 14 patients with hepatocellular carcinoma had genotype 1b. In the control group the distribution was: 1b, 287 patients (69.5%); 1a, 54 patients (12.1%); 3, 41 patients (9.9%); 4, 20 patients (4.8%), and genotype 2, 11 patients (2.7%). This differences in the distribution of genotypes between our population and the control group was statistically significant (P < .001). CONCLUSIONS: Genotype 1b, the most prevalent genotype in our liver transplant unit, included older patients in whom hepatocellular carcinoma was common, perhaps due to their higher prevalence of cirrhosis.

Results of liver transplantation in patients with previous portosystemic shunts.

INTRODUCTION: Although liver transplantation is performed successfully in some patients with previous portosystemic shunts (PSS), these surgical procedures have been considered a relative contraindication for orthotopic liver transplantation (OLT). We aimed to determine whether a previous PSS worsens the prognosis of patients who undergo OLT. PATIENTS AND METHODS: Between March 1986 and October 2003, 520 liver transplants were performed in 467 patients in our center. Thirteen patients had undergone a PSS before OLT. The types of PSS were: portocaval (n = 8), splenorenal (n = 3), mesocaval (n = 1), and portoatrial (n = 1). We compared patients with previous PSS (cases) and the three patients with an OLT immediately before each case (controls). We analyzed the following variables: age, Child-Pugh stage, pretransplant liver disease, surgical times, transfusion requirements, infections, intensive care unit (ICU) stay, postoperative evolution, and survival. RESULTS: Age, Child-Pugh stage, and pretransplant liver disease were similar in both groups. There were no statistical differences in age, surgical times, ischemia time, anhepatic phase, transfusion requirements, ICU stay, infections, or hospital stay. The postoperative course was similar in both groups. Long-term survival was 84.62% in cases versus 78.5% in controls. CONCLUSIONS: Previous PSS should not be considered a contraindication for liver transplantation, even though this group of patients involves a special surgical challenge.

Adefovir dipivoxil therapy in liver transplant recipients with lamivudine-resistant hepatitis B virus.

Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide. One effective strategy to prevent recurrence or transmission of HBV infection after liver transplantation exists is prescription of Lamivudine, although it is associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide analogue of adenosine that has achieved significant results in virologic, biochemical, and clinical parameters in lamivudine-resistant HBV-infected patients. Between 1990 and 2003 7 adult recipients of orthotopic liver transplants who experienced lamivudine-resistant HBV infection (pretransplantation or posttransplantation) were enrolled in a prospective study to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2 x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD, 1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end of the follow-up. HBe antigen seroconversion was observed in 1 patient. No significant adverse effects were recorded, except for renal functional impairment in 1 patient who had previous renal insufficiency. In our study, adefovir was an effective drug to suppression HBV replication in liver transplant recipients with lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of the drug was excellent. None of the patients developed resistance to adefovir. Therapy with AD in liver transplant recipients is effective and safe, although renal function should be monitored closely.

Five-year follow-up of a trial comparing Tacrolimus and cyclosporine microemulsion in liver transplantation.

We evaluate 5-year results of a prospective randomized trial that compared cyclosporine microemulsion (CsA-me) and Tacrolimus (Tac) for primary immunosuppression. One hundred one adult patients undergoing liver transplantation were randomized to receive Tac (n = 50) or CsA-me (n = 51). The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism. Survival rates at 1, 3, and 5 years were 86%, 75%, and 72%, respectively; there was no significant difference between CsA-me versus Tac arms. Acute rejection occurred in 30 cases (30%), independent of the type of primary immunosuppression. Serious adverse events were reported significantly more among patients under CsA-me (48 episodes) than under Tac (32 episodes). Nineteen patients were switched to the other calcineurin inhibitor. The switch was much more frequent from CsA-me to Tac (n = 15; 29.4%), mainly because of lack of efficacy (n = 10; 19.6%). There were no cases of chronic rejections in the Tac arm. Four patients were switched from Tac to CsA-me for side effects; only 1 remains alive, after treatment was changed from CsA-me to an antimetabolite. There were no statistical differences in renal dysfunction, diabetes, hypertension, neurologic disorders, new-onset malignancies, or infections. There were no differences in survival or rejection among the intention-to-treat groups. Serious adverse events, total patients with switch of calcineurin inhibitor, as well as switches due to lack of efficacy, were statistically more frequent under CsA-me. Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation.

Effectiveness of low-dose intramuscular anti-VHB immune globulin in the prophylaxis of viral B hepatitis reinfection after liver transplantation: preliminary report.

INTRODUCTION: Prophylaxis using high-dose intravenous anti-HBV immune globulin (HBIG) is effective to prevent reinfection due to hepatitis B virus (HBV) after orthotopic liver transplantation (OLT). However, this treatment is expensive and intravenous administration is difficult during outpatient care. Our aim was to assess the effectiveness of low-dose intramuscular HBIG to prevent HBV reinfection after OLT. PATIENTS: Six patients (all men, mean age 41 years, negative HBV DNA without hepatotropic virus coinfection) were transplanted in our institution due to HBV cirrhosis and included in a prospective noncomparative study. Intramuscular HBIG (2000 IU) was administered during the anhepatic phase of OLT, followed by daily 2000 IU doses for 7 days and then monthly. HBV antibody titers were measured every month. Reinfection was defined as the recurrence of surface HBV antigen in serum after transplantation. RESULTS: After 1 year follow-up, none of the six patients had detectable HBV surface antigen and the liver biopsies were normal in all cases. Using 2000 IU, anti-HBs levels were: 880+/-356 IU/L at 1 month, 191+/-123 at 6 months, and 225+/-49 after 1 year. In all cases anti-HBs titers were above 100 IU/L during the follow-up. CONCLUSIONS: Monthly administration of low-dose (2000 IU) intramuscular HBIG effectively prevents recurrence of HBV infection as well as attains a protective level of anti-HBs antibodies (over 100 IU/L) for at least the first year after transplantation.

Effectiveness and safety of mycophenolate mofetil as monotherapy in liver transplantation.

INTRODUCTION: Calcineurin inhibitors (CIs) cause substantial long-term morbidity and mortality among orthotopic liver transplantation (OLT) patients. Our aim was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) among OLT patients with CI-related side effects. PATIENTS: Thirty three adult patients, including 29 men and 4 women of mean age 57 years, underwent OLT between 1986 and 2000 under treatment with CIs (28 cyclosporine and five tacrolimus). Mean follow-up after OLT was 59 months. Adverse effects were renal dysfunction in 26, hypertension in 23, and neurotoxicity in two. MMF was added gradually while simultaneously reducing the dosage of CI. RESULTS: After a mean 15-months follow-up of MMF treatment, CIs had been withdrawn in 28 patients (85%). The mean time from the initiation of MMF and CI withdrawal was 5 months. During the first year of follow-up chronic renal dysfunction improved in 16 of 26 patients (61.6%) accompanied by a decreased serum creatinine and urea and an increase in creatinine clearance. Among 13/23 (56.5%) hypertensive patients, there was a significant decrease in blood pressure or the number of antihypertensive drugs (P<.05). One patient with neurotoxicity improved. Twenty-two patients (66%) displayed adverse events: five rejections (15%) including four acute episodes, controlled by CI re-introduction, and one chronic reaction. The most frequent adverse effects were herpes simplex infection in 10 patients (30%), asthenia in nine (27%), diarrhea in five (15%) and thrombocytopenia in four (12%). Nevertheless, only six patients (19%) required MMF dose reduction, namely, three patients with GI intolerance, two with repeated VHS infections, and one with anemia. CONCLUSIONS: MMF monotherapy improves renal function and blood pressure levels in more than 50% of patients with chronic renal impairment and hypertension after OLT. Many of the side effects of MMF were mild; it was safe accompanied by a low incidence of rejection reactions.

[Acute lower massive digestive hemorrhage due to a jejunal angiomatoid hamartoma. Case report]. / Hemorragia digestiva baja aguda masiva debida a hamartoma angiomatoide yeyunal. Aportación de un caso.

Acute hemorrhage of the lower digestive tract is massive in 20% of the cases, requiring emergency surgery. In such cases, a preoperative diagnosis of the point of bleeding is essential. In order to determine this, any combination of oral panendoscopy, rectal sigmoidoscopy, colonoscopy, arteriography and isotopic studies should be used. The most frequent causes are right colonic angiodysplasia and colonic diverticulosis. The authors present a case of lower digestive bleeding due to an angiomatoid hamartoma located in the first jejunal segments, a rare pathology as a cause of hemorrhage. The diagnosis was obtained by selective arteriography. Oral panendoscopy and colonoscopy were also performed.

[Hemoperitoneum secondary to acute cholecystitis in kidney transplant]. / Hemoperitoneo secundario a colecistitis aguda en el trasplante renal.

We present two cases of acute cholecystitis occurring more than two years after renal transplantation. The course of the acute event was complicated by the presence of hemobilia in one of the patients and severe hemoperitoneum in both patients. We comment the possible etiologic factors, the high efficiency of the diagnostic procedures and the importance of prompt cholecystectomy as the best treatment method.

[Surgical evaluation of a liver transplant program. Experiences with the first 45 cases]. / Evaluación quirúrgica de un programa de trasplante hepático. Experiencia de los 45 primeros casos.

The cumulative experience in liver transplantation since the introduction of cyclosporine A has confirmed its efficacy in the treatment of diverse liver diseases in children and adults. In the present study we review the surgical aspects of 45 transplants performed in 39 patients (17 children and 22 adults). Immunosuppressive treatment consisted of cyclosporine A, steroids and monoclonal antibodies (OKT3) in rejection unresponsive to steroids. The actuarial survival rate one year after transplantation was 74%. In the course of development of the program, the elective use of veno-venous bypass during the anhepatic phase in adults was confirmed as useful. Among pediatric transplantations there were numerous arterial malformations (31.5%) in donor organs, which, with the malformations associated in receptors, made allograft reconstruction difficult. Our results confirm those reported by other groups, as well as the importance of specialized training for this type of intervention.