Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no longer considered an absolute contraindication to curative hepatic resection. A growing number of observational analyses have illustrated the feasibility of such resections; however, the evidence base is at best heterogeneous with a lack of evidence comparing similar patient groups. We aimed to evaluate the outcomes of hepatectomy for CRLM when combined with other viscera and compare to a matched cohort of isolated hepatic resections.From 2005 to 2015, 523 patients underwent hepatic resection for CRLM at our institution, 19 of whom underwent hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was performed between those who underwent isolated hepatectomy (control group) and those who underwent hepatectomy with extrahepatic resection (combined group). Clinicopathological data were reviewed along with 30-day postoperative morbidity and mortality. Furthermore, overall survival for the multivisceral cohort was compared to all other isolated hepatectomies over the same time period.Nineteen patients underwent liver resection accompanied by either/or diaphragmatic resection (n = 13), major vein resection and reconstruction (n = 5), and visceral resection (n = 3). Maximum tumor size was significantly larger in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3- and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival showed no significant difference between combined and control groups (p = 0.78). Similarly, when compared to the total cohort of isolated liver resections (n = 504), no significant difference in overall mortality was noted.In patients presenting with concomitant CRLM and extrahepatic extension where R0 margins can be achieved, this present study supports the rationale to proceed to -surgery with comparable morbidity and mortality rates to -isolated hepatectomy.
Background: Sirolimus is an antibiotic with antifungal, antifibrotic and immunosuppressant properties that has been used in orthotopic liver transplantation (OLT) as substitute of calcineurin inhibitors (CNI) in cases of de novo tumors, patients subjected to OLT for hepatocellular carcinoma (HCC) and nephrotoxicity due to CNI. We present our experience with sirolimus monotherapy in OLT Patients and methods: Between April 1986 and December 2010 we performed 1500 OLT, of whom 57 patients are receiving immunosuppressive treatment with sirolimus, and 39 of them are currently in monotherapy. We analized the clinical characteristics of patients, associated side effects, rejection rate, renal function and lipid profile, in patients treated with sirolimus monotherapy. Results: There were 31 males (79.5%), and 8 females (20.5%) with a mean age at OLT of 50.5 ±10.5 years. The mean follow-up period was 89.8 months. The main indications for OLT was alcoholic cirrhosis in 10 patients (25.6%), HCV cirrhosis in 5 (12.8%), and HCV cirrhosis+HCC in 5 (12.8%). Other causes were HBV cirrhosis, acute liver failure, autoimmune hepatitis. The most frequently immusosuppressive therapy used at discharge was tacrolimus+prednisone in 25 patients (64.1%). Premonotherapy immunosuppression most frequently used was tacrolimus+sirolimus in 21 patients (53.9%), and mycophenolate+sirolimus in 15 (38.5%). The mean time from OLT to sirolimus monotherapy treatment initiation was 65.3 months, and the mean follow-up after switching to sirolimus monotherapy was 22.8 months. Only 1 patient (2.6%) presented acute rejection, being with adequate drug levels, and treated with reintroduction of tacrolimus. The indications for conversion to sirolimus monotherapy were: de novo aerodigestive tract tumors in 11 patients (28.3%), HCC in 10 (25.6%), nephrotoxicity due to CNI in 5 (12.8%), skin malignacies in 4 (10.3%), lymphoproliferative disorders in 3 (7.7%), urologic tract tumors in 3 (7.7%), central nervous system tumors in 2 (5%) and gynecological in 1 patient (2.6%). Adverse effects developed in 35 patients (89.7%) and the most frequent were: dyslipidemia in 24 patients (61.5%), edemas in 8 (20.5%), and cytopenias in 8 (20.5%). The mean creatinine clearance rate (CCL) before sirolimus therapy was 69.9 ml/min (normal kidney function in 30.8% of patients, mild renal insufficiency in 48.7%, and moderate in 20.5%); and after monotherapy was 75.3 ml/min (normal kidney function in 38.5% of patients, mild renal insufficiency in 41%, moderate in 18%, and severe in 2.6%) (p=0.0001). Total cholesterol and trigliceride values increased significantly after switching: cholesterol 171 mg/dl vs 208 mg/dl (p=0.002); and trigliceride 108 mg/dl vs 158 mg/dl (p=0.015). Seventeen patients were treated with hypolipemiant drugs. Conclusions: Sirolimus monotherapy is a good immunosuppressive option in patients who underwent OLT for HCC or those who develop de novo tumors or nephrotoxicity due to CNI. Monotherapy is well tolerated and is associated with low rejection rate. Renal function improves after conversion to sirolimus monotherapy and dyslipidemia is pharmacologically well controlled.
Background: Everolimus is a potent immunosuppressant which have several advantages over calcineurin inhibitors (CNI): good tolerance, preventive effects on cardiovascular morbidity and mortality, as well as cancer prevention due to cell proliferation inhibition. It is particularly suitable for patients with liver transplant due to hepatocellular carcinoma (HCC), de novo malignancies or renal insufficiency. We analyze our experience with the use and management of everolimus monotherapy in orthotopic liver transplantation (OLT). Patients and methods: Between April 1986 and December 2010 we performed 1500 OLT in our institution. Everolimus was introduced into clinical use at the end of 2005. Fifty-seven patients received immunosuppression with everolimus, and 24 of these are currently in monotherapy. We analyze side effects, acute rejection, renal insufficiency, lipid profile as well as tolerance and indication for use. Results: There were 19 males (79.2%) and 5 females (20.8%). The main indication for OLT was alcoholic cirrhosis in 6 patients (25%), and other indications were HCV, HBV and HCC. Hepatocellular carcinoma (37.5%), lymphoproliferative diseases (21%), and de novo digestive and respiratory tract tumors (21%) were the main causes of switching to everolimus. The majority of our patients (54.2%) received tacrolimus+prednisone as initial immunosuppressive therapy, initiating monotherapy with everolimus at a mean time of 71.8 months after OLT. The mean follow-up after switching to everolimus monotherapy was 10.3 months. There were no differences in terms of renal or hepatic functions after everolimus monotherapy. We found lipid profile higher in comparison with it before everolimus: mean cholesterol level before everolimus was 170 mg/dl and 175 mg/dl after; mean triglycerides before monotherapy was 103 mg/dl and 135 mg/dl after. Eight patients are treated with hypolipemiants. Mean creatinine clearance rate (CCL) premonotherapy was 70.42 ml/min, and postmonotherapy was 76.24 ml/min (p=0.091). There was only one patient who showed acute rejection in the presence of adequate drug levels, successfully treated with tacrolimus reintroduction. Adverse effects were observed in 15 patients (62.5%), and the most frequent were dyslipidemia (8 patients) and edemas (5 patients). Conclusions: Everolimus monotherapy is a good immunosuppressive option in OLT patients with recurrent or de novo malignancies, or with renal dysfunction. Everolimus monotherapy is associated with low rejection rate and improvement of renal function. The most frequent side effects are hyperlipidemia and edemas, but usually well tolerated by the patients or controlled with pharmacological treatment.
El presente estudio evaluó el control que ejerce el mantenimiento o cancelación de estímulos correlacionados con periodos de reforzamiento y de extinción sobre la tasa y distribución temporal del responder en programas definidos temporalmente. Se expuso a nueve palomas a un ciclo T de reforzamiento (60 s) donde cada subciclo (Td y T∆) duró 30 s. El estimulo correlacionado con Td fue una luz verde y el correlacionado con T∆, una luz roja. Para tres palomas el estímulo de cada subciclo se canceló con la emisión de la primera respuesta (Sin luz 'Id-Té), para otras tres palomas se canceló el estímulo correlacionado con Td, mientras que el correlacionado con T∆, permaneció encendido durante todo el subciclo (Sin luz Td); para las tres palomas restantes el estímulo correlacionado con Td permaneció encendido y se canceló el estímulo correlacionado con T∆, (Sin luz T∆). Los resultados mostraron que el control del responder es ejercido por el mantenimiento de los estímulos independientemente de su correlación con un periodo de reforzamiento o extinción. Los resultados se discuten en términos de la presencia vs. ausencia de la señal mas que como una función de la contingencia estímulo-respuesta-reforzador.
Background: Sirolimus is a macrocyclic antibiotic with antifungal, antifibrotic and immunosuppressive properties that can inhibit metastatic tumor growth and angiogenesis in vivo mouse models. It can be used as a substitute for calcineurin inhibitors (CNI) because it may reduces the likelihood of recurrent hepatocellular carcinoma (HCC) or the rate of de novo tumors in high risk transplant patients. Sirolimus protects allografts from rejection while simultaneously inhibits tumor growth. Patients and methods: Between April 1986 and December 2010 we performed 1500 orthotopic liver transplants (OLT). Fifty-seven patients received immunosuppressive treatment with sirolimus, and 26 patients of them due to de novo tumors. Currently, 20 of these patients are with sirolimus monotherapy. We analyze the outcome of liver transplant recipients who developed de novo tumors and were treated with sirolimus monotherapy. Results: There were 20 patients (18 males and 2 females), with a mean age at OLT of 50.3±12.1 years, and mean follow-up of 111.5 months. The main indications for OLT were alcoholic cirrhosis (40%), and HCV cirrhosis (15%). The most frequently immunosuppressive therapy used at discharge was tacrolimus+prednisone (55%). Premonoterapy immunosuppression most frequently used was tacrolimus+sirolimus (50%), and mycophenolate+sirolimus (40%). The mean time from OLT to sirolimus treatment was 74.6 months, and from then until the beginning of monotherapy was 9.5 months with a mean time of 24.7 months in monotherapy. The location of de novo tumors was: aerodigestive tract (45%), skin (20%), lymphoproliferative disorders (15%), urologic tract (10%), gynecological (5%), and central nervous system (5%). There was only one case of rejection (5%) in the presence of adequate drug levels, successfully treated with reintroduction of tacrolimus. Adverse effects were seen in 80% of patients, and the most frequent were: dyslipidemia (11 patients), edema (5 patients), and oral thrush (4 patients). Regarding lipid profile, mean cholesterol value before sirolimus was 168 mg/dl, and postmonotherapy was 211 mg/dl (p =0.0001). Seven patients are treated with hypolipemiant. Mean value of pre-sirolimus triglycerides was 104 mg/dl and post-monotherapy was 130 mg/dl (p=0.071). Regarding renal function, mean creatinine clearance pre-sirolimus was 70.6 ml/min and post-monotherapy was 75.6 ml/min (p>0.05). Conclusions: Sirolimus is a potent immunosuppressant with antitumoral properties, with low rate of rejection, which represents a good option OLT with de novo malignancies. More than half of the patients presented side effects, but they were well tolerated or controlled with medical treatment (dyslipidemia as the most frequent). There was an improvement of renal function showing an increase in creatinine clearance.
La perforación asociada a infección intraabdominal difusa por Candida spp. es excepcional. Suele asociarse a pacientes inmunodeprimidos o con enfermedad tumoral avanzada. Presentamos 2 casos de perforación digestiva secundaria a candidiasis invasiva. En el primer caso, una mujer de 68 años con una perforación duodenal secundaria a Candida spp., se realiza laparotomía exploradora y reparación de la perforación duodenal. Sin embargo, la paciente requiere más de 2 intervenciones, observándose Candida spp. macroscópica diseminada por toda la cavidad abdominal. El segundo caso es el de un varón de 60 años que presenta un postoperatorio complicado de una hemicolectomía derecha, que se asocia con pancretitis, y con posterior diseminación fúngica abdominal secundaria a Candida parapsilopsis, con múltiples complicaciones infecciosas. En ambos casos se intentó un tratamiento basado en resección quirúrgica y cambio de antifúngicos, sin éxito. El tratamiento antifúngico precoz evita la diseminación hematógena y el shock séptico, disminuyendo la morbimortalidad de estos pacientes. Candida spp. as cause of diffuse intraabdominal infection is very rare. Often associated with immunocompromised or patients with advanced tumor disease. We are reporting 2 cases of gastrointestinal perforation secondary to invasive candidiasis. The first case, a 68 years old female with a Candida spp. duodenal perforation. An emergency exploratory laparotomy was performed and a duodenal perforation repair was done. However, the patient required 2 more reoperation due to Candida spp. macroscopic intra-abdominal disemination. The second case, is presented in the context of a postoperative period of a right hemicolectomy, pancreatitis associating abdominal spread and subsequent secondary fungal Candida parapsilopsis with multiple infectious complications. In both cases there were unsuccessful surgical resection and antifungal change. The early antifungal treatment prevents hematogenous dissemination and septic shock, reducing the morbidity and mortality of these patients.
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