Oleic acid regulates the circadian rhythm of adipose tissue in obesity.

The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.

Oleic acid restores the rhythmicity of the disrupted circadian rhythm found in gastrointestinal explants from patients with morbid obesity.

BACKGROUND & AIMS: We investigated whether oleic acid (OA), one of the main components of the Mediterranean diet, participates in the regulation of the intestinal circadian rhythm in patients with morbid obesity. METHODS: Stomach and jejunum explants from patients with morbid obesity were incubated with oleic acid to analyze the regulation of clock genes. RESULTS: Stomach explants showed an altered circadian rhythm in CLOCK, BMAL1, REVERBα, CRY1, and CRY2, and an absence in PER1, PER2, PER3 and ghrelin (p > 0.05). OA led to the emergence of rhythmicity in PER1, PER2, PER3 and ghrelin (p < 0.05). Jejunum explants showed an altered circadian rhythm in CLOCK, BMAL1, PER1 and PER3, and an absence in PER2, REVERBα, CRY1, CRY2 and GLP1 (p > 0.05). OA led to the emergence of rhythmicity in PER2, REVERBα, CRY1 and GLP1 (p < 0.05), but not in CRY2 (p > 0.05). OA restored the rhythmicity of acrophase and increased the amplitude for most of the genes studied in stomach and jejunum explants. OA placed PER1, PER2, PER3, REVERBα, CRY1 and CRY2 in antiphase with regard to CLOCK and BMAL1. CONCLUSIONS: There is an alteration in circadian rhythm in stomach and jejunum explants in morbid obesity. OA restored the rhythmicity of the genes related with circadian rhythm, ghrelin and GLP1, although with slight differences between tissues, which could determine a different behaviour of the explants from jejunum and stomach in obesity.

Predictive Models of Hepatocellular Carcinoma Recurrence After Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is a curative treatment for patients with hepatocellular carcinoma who are not candidates for resection. Despite the generalized use of the Milan criteria and up-to-seven criteria, new markers have been proposed to predict recurrence after LT. Biomarkers such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and scores such as the Model of Recurrence After Liver transplantation (MORAL) are used as predictors of post-LT recurrence. OBJECTIVE: We aim to compare NLR, PLR, and MORAL score with Milan criteria and up-to-seven criteria. METHODS: A descriptive study of 99 patients who underwent LT for hepatocellular carcinoma in our hospital between April 2010 and April 2016. The 5 prognostic models were applied to the patients to stratify them into risk groups. We used a Kaplan-Meier survival plot to measure recurrence-free survival in each model. Receiver operative curves were used to compare the models. RESULTS: Three-year recurrence-free survival in MORAL was 91.1% for the low-risk group, 89.8% for the moderate-risk group, 60% for the high-risk group, and 75% for the very high-risk group (P = .003). The combined MORAL score was superior in predicting 1- and 3-year recurrence with the area under the curve 0.684 (95% confidence interval [CI]: 0.52-0.85) compared with Milan (0.536 [95% CI: 0.37-0.70]), up-to-seven (0.601 [95% CI: 0.43-0.77]), PLR (0.452 [95% CI: 0.30-0.61]), and NLR (0.542 [95% CI: 0.37-0.71]). CONCLUSIONS: A model based only on pre-LT radiological signs leads to underdiagnosis of tumor load; therefore, the risk of recurrence must be recalculated after LT. The combined MORAL score was the best prognostic model of 1- and 3-year recurrence after LT in our study.

A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity.

OBJECTIVE: The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG). RESEARCH DESIGN AND METHODS: Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM). RESULTS: MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFß and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05). CONCLUSIONS: There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.

Increased PON lactonase activity in morbidly obese patients is associated with impaired lipid profile.

AIMS: The paraoxonase-1 (PON1) enzyme could play an important role in the anti-oxidant capacity of high-density lipoprotein. However, there are no studies which analyse the evolution of the three activities of PON1 (PON arylesterase, PON paraoxonase and PON lactonase) after Roux-en-Y Gastric Bypass (RYGB) in morbidly obese subjects. We analysed the association of PON concentration and activities with the evolution of morbidly obese subjects who underwent RYGB, and its relationship with biochemical variables and different atherogenic indices. METHODS: Twenty-seven non-obese and 82 morbidly obese subjects were studied before and 6 months after RYGB. RESULTS: Before RYGB, morbidly obese subjects had a lower PON1 concentration (P < 0.05) and higher PON lactonase activity (P < 0.001) than non-obese subjects, with no differences in PON arylesterase and PON paraoxonase activities. After RYGB, PON1 concentration (P < 0.05) and PON lactonase activity (P < 0.001) decreased with regard to the presurgery state. PON lactonase activity correlated with the atherogenic index of plasma before (r = 0.19, P = 0.047) and after RYGB (r = 0.27, P = 0.035). In different multiple lineal regression analysis models, presurgery PON lactonase activity was associated with total cholesterol (ß = 0.909, P < 0.001), LDL (ß = 0.632, P = 0.006) and DBP (ß = 0.230, P = 0.030) (R2  = 0.295), postsurgery PON lactonase activity was associated with esterified cholesterol (ß = 0.362, P = 0.011) (R2  = 0.131), and the change (Δ) in PON lactonase activity after RYGB was associated with Δesterified cholesterol (ß = 0.304, P = 0.030) (R2  = 0.093). CONCLUSIONS: PON lactonase activity is associated with the presence of morbid obesity and with an impaired lipid profile. All associations found could indicate the relationship between PON lactonase activity and the development of atherosclerosis.

Posterior approach (Kraske procedure) for surgical treatment of presacral tumors.

Presacral tumors are rare, but can comprise a great variety of histological types. Congenital tumors are the most common. Once the diagnosis is established, surgical resection is essential because of the potential for malignancy or infection. Previous biopsy is not necessary or may be even harmful. To decide the best surgical approach (abdominal, sacral or combined) an individual and multidisciplinary analysis must be carried out. We report three cases of cystic presacral masses in which a posterior approach (Kraske procedure) enabled complete resection, the only way to decrease local recurrence. All patients had a satisfactory recovery. A brief overview of retrorectal tumors is presented, focusing on classification, clinical presentation, diagnosis and surgical management.

Tratamiento agresivo de las complicaciones arteriales del trasplante hepático. Impacto sobre la supervivencia y las complicaciones biliares / Aggressive management of the arterial complications of liver transplantation. Impact upon survival and biliary complications

Se estudian las complicaciones arteriales (CA) ocurridas en 400 trasplantes realizados entre 1997 y 2006. Se dividen en 2 grupos según el tipo de tratamiento realizado: grupo i: tratamiento invasivo (tratamiento sobre la arteria o retrasplante), y grupo ii: tratamiento conservador o sintomático. Se analizan el impacto del tratamiento sobre la supervivencia y las complicaciones biliares (CB).Resultados Se han presentado 18 CA (4,5%), 10 complicaciones precoces (7 trombosis y 3 estenosis) y 8 complicaciones tardías (5 trombosis y 3 estenosis). El 90% de las complicaciones precoces se trató de forma invasiva (4 trombectomías urgentes, un retrasplante, 3 angioplastias y una ligadura de arteria hepática), y el 25% de las complicaciones tardías se trató con retrasplante (3); el 75% restante recibió tratamiento sintomático. Resultados La supervivencia a 12 y 60 meses fue inferior en el grupo ii (el 57 y el 42%) que en el grupo i (el 90 y el 68%), aunque sin alcanzar significación estadística. La tasa global de CB de enfermos con trombosis arterial fue del 50%. En el grupo i del %, significativamente menor que el grupo ii con el 71% (p<0,04).Conclusiones El tratamiento invasivo de las CA en el trasplante hepático se asocia a una mayor supervivencia a corto plazo y reduce de forma significativa la aparición de CB. En nuestra experiencia, los pacientes se benefician de un diagnóstico precoz y un tratamiento intensivo en este tipo de complicaciones (AU)

Abstract A study was made of the arterial complications documented in 400 transplants performed between 1997 and 2006. The patients were divided into two groups according to the type of treatment provided. Group I: invasive management (arterial treatment or re-transplant), and Group II: conservative or symptomatic management. The impact of management upon survival and biliary complications was analysed. Results There were 18 arterial complications (4.5%): 10 early (7 thromboses and 3 stenoses) and 8 late (5 thromboses and 3 stenoses). Ninety percent of the early complications were subjected to invasive management (4 emergency thrombectomies, 1 re-transplant and 3 angioplasties), while 25% of the late complications were treated in the form of re-transplant and the remaining 75% were subjected to symptomatic treatment. Survival after 12 and 60 months was lower in Group II (57% and 42%) than in Group I (90% and 68%), although without reaching statistical significance. The overall biliary complications rate among the patients with arterial thrombosis was 50%. The rate was significantly lower in Group I than in Group II (10% versus 71%) (P<04).Conclusions Invasive management of the arterial complications of liver transplantation is associated with longer short-term survival and significantly fewer biliary complications. In our experience, patients benefit from an early diagnosis and aggressive management of complications of this kind (AU)

[Aggressive management of the arterial complications of liver transplantation. Impact upon survival and biliary complications]. / Tratamiento agresivo de las complicaciones arteriales del trasplante hepático. Impacto sobre la supervivencia y las complicaciones biliares.

UNLABELLED: A study was made of the arterial complications documented in 400 transplants performed between 1997 and 2006. The patients were divided into two groups according to the type of treatment provided. Group I: invasive management (arterial treatment or re-transplant), and Group II: conservative or symptomatic management. The impact of management upon survival and biliary complications was analysed. RESULTS: There were 18 arterial complications (4.5%): 10 early (7 thromboses and 3 stenoses) and 8 late (5 thromboses and 3 stenoses). Ninety percent of the early complications were subjected to invasive management (4 emergency thrombectomies, 1 re-transplant and 3 angioplasties), while 25% of the late complications were treated in the form of re-transplant and the remaining 75% were subjected to symptomatic treatment. Survival after 12 and 60 months was lower in Group II (57% and 42%) than in Group I (90% and 68%), although without reaching statistical significance. The overall biliary complications rate among the patients with arterial thrombosis was 50%. The rate was significantly lower in Group I than in Group II (10% versus 71%) (P<04). CONCLUSIONS: Invasive management of the arterial complications of liver transplantation is associated with longer short-term survival and significantly fewer biliary complications. In our experience, patients benefit from an early diagnosis and aggressive management of complications of this kind.