Norberto Cassinello

Contribution of hyperammonemia and inflammatory factors to cognitive impairment in minimal hepatic encephalopathy

To assess the contribution of hyperammonemia and inflammation to induction of mild cognitive impairment (or MHE). We analyzed the presence of mild cognitive impairment (CI) by using the PHES battery of psychometric tests and measured the levels of ammonia and of the inflammatory cytokines IL-6 and IL-18 in blood of patients with different types of liver or dermatological diseases resulting in different grades of hyperammonemia and/or inflammation. The study included patients with 1) liver cirrhosis, showing hyperammonemia and inflammation; 2) non-alcoholic fatty liver disease (NAFLD) showing inflammation but not hyperammonemia; 3) non-alcoholic steatohepatitis (NASH) showing inflammation and very mild hyperammonemia; 4) psoriasis, showing inflammation but not hyperammonemia; 5) keloids, showing both inflammation and hyperammonemia and 6) controls without inflammation or hyperammonemia. The data reported show that in patients with liver diseases, cognitive impairment may appear before progression to cirrhosis if hyperammonemia and inflammation are high enough. Five out of 11 patients with NASH, without liver cirrhosis, showed cognitive impairment associated with hyperammonemia and inflammation. Patients with keloids showed cognitive impairment associated with hyperammonemia and inflammation, in the absence of liver disease. Hyperammonemia or inflammation alone did not induce CI but the combination of certain levels of hyperammonemia and inflammation is enough to induce CI, even without liver disease.

Oxidative and nitrosative stress in acute pancreatitis. Modulation by pentoxifylline and oxypurinol.

Reactive oxygen species are considered mediators of the inflammatory response and tissue damage in acute pancreatitis. We previously found that the combined treatment with oxypurinol - as inhibitor of xanthine oxidase- and pentoxifylline - as inhibitor of TNF-α production-restrained local and systemic inflammatory response and decreased mortality in experimental acute pancreatitis. Our aims were (1) to determine the time-course of glutathione depletion and oxidation in necrotizing pancreatitis in rats and its modulation by oxypurinol and pentoxifylline; (2) to determine whether TNF-α is responsible for glutathione depletion in acute pancreatitis; and (3) to elucidate the role of oxidative stress in the inflammatory cascade in pancreatic AR42J acinar cells. We report here that oxidative stress and nitrosative stress occur in pancreas and lung in acute pancreatitis and the co-treatment with oxypurinol and pentoxifylline prevents oxidative stress in both tissues. Oxypurinol was effective in preventing glutathione oxidation, whereas pentoxifylline abrogated glutathione depletion. This latter effect was independent of TNF-α since glutathione depletion occurred in mice deficient in TNF-α or its receptors after induction of pancreatitis. The beneficial effects of oxypurinol in the inflammatory response may also be ascribed to a partial inhibition of MEK1/2 activity. Pentoxifylline markedly reduced the expression of Icam1 and iNos induced by TNF-α in vitro in AR42J cells. Oxidative stress significantly contributes to the TNF-α-induced up-regulation of Icam and iNos in AR42J cells. These results provide new insights into the mechanism of action of oxypurinol and pentoxifylline as anti-inflammatory agents in acute pancreatitis.

Predictors of psychological symptoms in morbidly obese patients after gastric bypass surgery

BACKGROUND Morbid obesity is associated with debilitating psychosocial consequences, such as depression, anxiety, and low self-esteem. One of the main goals of bariatric surgery should not only be reducing weight and counteracting co-morbid conditions, but also improving postoperative psychosocial functioning. The objective of our study was to determine the preoperative variables that could predict the psychological symptoms 6 and 12 months after surgery to improve the clinical outcome of morbidly obese patients undergoing bariatric surgery. The setting was a university hospital in Spain. METHODS The study group consisted of 60 morbidly obese patients (46 women and 14 men) who had undergone gastric bypass surgery for weight reduction and had ≥ 1 year of follow-up. The patients were evaluated using different questionnaires (Symptom Checklist-90-Revised, Body Shape Questionnaire, Rosenberg Self-Esteem Questionnaire, COPE, Medical Outcomes Study Social Support Survey) at 3 points: before surgery, at 6 months postoperatively, and at 1 year postoperatively. To determine the influence of preoperative variables on long-term psychological status, a step-by-step multivariate linear regression analysis was performed, taking P < .05 as statistically significant. RESULTS The variables of self-esteem, instrumental support, and coping focused in the emotions were the main preoperative predictors for psychological symptoms 6 months after surgery. Preoperative drug abuse as a strategy of problem solving and mainly body image significantly predicted most of the psychological disorders 1 year after surgery. CONCLUSION The study of different psychosocial variables in patients before bariatric surgery is an important aid to predict postoperative psychological functioning. Self-esteem and body image were the most influential factors in the postoperative psychological outcome of morbidly obese patients in our study.

Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity

In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase‐generated cytokeratin‐18 (CK‐18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase‐generated CK‐18 fragments in patients with severe obesity.

Computerized acoustic voice analysis and subjective scaled evaluation of the voice can avoid the need for laryngoscopy after thyroid surgery.

BACKGROUND Because of frequent postoperative alterations in voice, many surgeons include laryngoscopy as a routine examination before/after thyroid surgery. The aim of this work was to determine whether more comfortable and easier subjective or objective postoperative voice assessments could complement or replace laryngoscopy. METHODS Sixty-four consecutive patients scheduled to undergo thyroid surgery underwent preoperative objective computerized acoustic voice analysis (CAVA), subjective scaled evaluation of the voice (SSEV) with the GIRBAS scale, and fiberoptic laryngoscopy. All patients had 7- and 30-day postoperative follow-up assessments using the same tests. RESULTS CAVA measurements of jitter and noise-to-harmonic ratio showed the most frequent variations (36% and 31%, respectively) between the first and second tests. The mean preoperative SSEV GIRBAS value was 1.3 (range, 0-7) and had deteriorated in 36% of patients at 30 days postoperatively. All patients had a normal preoperative laryngoscopy. At 7 days postoperatively, 5 (8%) patients suffered unilateral vocal cord palsy which recovered in 2 (5%) patients after 1 month. GIRBAS values showed differences between patients with and without a vocal cord palsy both 7 and 30 days postoperatively (P < .05). The vocal parameters jitter and shimmer showed differences (P < .02 each) between patients with or without vocal cord palsy. When there was a change in >or=3 vocal parameters, vocal cord palsy was confirmed by laryngoscopy. CONCLUSION After thyroid surgery, vocal cord palsy may be suspected when there is an alteration in GIRBAS scale or in several parameters of the CAVA. Laryngoscopy may only be necessary when the CAVA and SSEV are abnormal.

Alterations in adipocytokines and cGMP homeostasis in morbid obesity patients reverse after bariatric surgery.

Obesity‐associated nonalcoholic fatty liver disease (NAFLD), covering from simple steatosis to nonalcoholic steatohepatitis (NASH), is a common cause of chronic liver disease. Aberrant production of adipocytokines seems to play a main role in most obesity‐associated disorders. Changes in adipocytokines in obesity could be mediated by alterations in cyclic GMP (cGMP) homeostasis. The aims of this work were: (1) to study the role of altered cGMP homeostasis in altered adipocytokines in morbid obesity, (2) to assess whether these alterations are different in simple steatosis or NASH, and (3) to assess whether these changes reverse in obese patients after bariatric surgery.

What are obese patients able to eat after Roux-en-Y gastric bypass?

Background/Aims: The goal of this study was to analyze the likelihood of patients undergoing Roux-en-Y gastric bypass (RYGB) to recover a normal daily food intake, and the possible influence of dietary and exercise habits on long-term weight loss. Methods: The sample included 107 morbidly obese postoperative patients with at least 1 year of follow-up. The data collected included anthropometry, dietary and exercise habits, and information on ingested food. The unpaired Student’s t test and the multivariate step-by-step regression were used in the analysis. Results: The mean preoperative BMI was 50.7 ± 11.8 kg/m2, which had decreased at the moment of survey to 31.7 ± 5.4 kg/m2. The mean % Excess of BMI Lost (%EBMIL) was 77.4 ± 23.7%. The nutritional components of diet were similar to those for the nonobese population. There were no significant differences in %EBMIL regarding number of meals, social habits, components of diet, or amount of exercise. The daily mean caloric intake (1,364 ± 293 kcal) was the only parameter significantly related to the %EBMIL outcome. More than 30% of the patients had intolerance to certain foods. Conclusion: Obese patients undergoing RYGB can establish a postoperative lifestyle and diet similar to the ideal. Only the daily amount of ingested calories demonstrated a statistically significant influence on weight loss over time.

Esophageal abnormalities in morbidly obese adult patients

BACKGROUND An increase in body mass index has been found to be associated with an increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. Few systematic studies with objective tests have evaluated esophageal disorders in the morbidly obese population. OBJECTIVES To define more precisely in morbidly obese people the incidence of esophageal symptoms and characterize the esophageal disorders using objective data. SETTING University Hospital, Spain. METHODS Two hundred twenty-four presurgical morbidly obese patients were submitted to a protocol including a clinical history and objective tests (endoscopy, stationary esophageal manometry, 24-hour esophageal pH monitoring and isotopic emptying of the esophagus). RESULTS In a morbidly obese population, heartburn (50.9%) and regurgitation (28.6%) were the most prevalent symptoms of GERD. Endoscopy registered hiatus hernia (12.5%) and reflux esophagitis (17.3%). Manometry was often abnormal (33.4%), with a hypotensive lower esophageal sphincter as the most common finding. Esophageal pH-metry was abnormal in 54.2% of the cases. Finally, 9.1% of the patients presented with abnormal isotopic esophageal emptying. A correlation between the degree of obesity and the severity of symptoms/objective tests for esophageal abnormalities could not be found. CONCLUSIONS In morbidly obese patients, GERD is common, symptoms are unspecific, and there is a high prevalence of pH-metry and manometric abnormalities, unrelated to the degree of obesity.

Requirement and postoperative outcomes of abdominal panniculectomy alone or in combination with other procedures in a bariatric surgery unit

BACKGROUND A high percentage of patients present with redundant skin folds after bariatric surgery. This study aims to quantify the need for panniculectomy after open bariatric surgery and to analyze the postoperative outcomes. METHODS A retrospective cohort study was performed. The patients were divided into 2 groups: group DLP, patients who underwent an abdominal panniculectomy alone and group DLP+, those who underwent panniculectomy in association with another surgical procedure. RESULTS Four hundred forty-six patients underwent open bariatric surgery and 130 patients (29%) subsequently required an abdominal dermolipectomy. Seventy-six percent presented also incisional hernia and 8% presented cholelithiasis. Forty-six percent of patients presented postoperative complications: wound seroma/infection (21%), wound dehiscence due to skin necrosis (13%), and hemorrhage/hematoma (10%) were the most frequent. There were no major complications or mortality. DLP+ was not associated with an increase in complications. CONCLUSIONS After open bariatric surgery, an abdominal panniculectomy is often required. This procedure has a high postoperative morbidity in these patients, although complications are usually mild. There is not an increase in the rate of complications when panniculectomy is associated with other procedures.

Efecto de la quimioterapia neoadyuvante en los resultados de la cirugía de resección de las metástasis hepáticas de origen colorrectal

Resumen Introduccion La cirugia es el tratamiento de eleccion de los pacientes con metastasis hepaticas de cancer colorrectal, pero solo un 10-20% de los casos son resecables. El uso de quimioterapia neoadyuvante puede rescatar para la cirugia a pacientes inicialmente considerados irresecables. El objetivo de este trabajo es comparar los resultados de la reseccion de metastasis hepaticas de origen colorrectal en pacientes con y sin quimioterapia neoadyuvante. Pacientes y metodo Se ha estudiado a 105 pacientes intervenidos por metastasis hepaticas de cancer colorrectal, divididos en dos grupos segun la estrategia de tratamiento: cirugia en los pacientes inicialmente considerados resecables (grupo C) y quimioterapia neoadyuvante mas cirugia (grupo QT+C) en los que inicialmente se considero irresecables y que tras quimioterapia se convirtieron en resecables. Se ha comparado la edad y el sexo, el origen del tumor primario, el tiempo de aparicion, el numero, el tamano maximo y la localizacion de las metastasis, CEA, el margen de reseccion, la morbilidad y la mortalidad postoperatorias, el tiempo de ingreso, la tasa de recidivas y la supervivencia en general y la libre de enfermedad. Resultados Al comparar a los dos grupos, C y QT+C, han resultado significativas la presencia de metastasis sincronicas (el 30,8 y el 77,4%), la distribucion bilobar (el 13,5 y el 58,5%), el numero y el tamano de las metastasis (1 contra 3 nodulos y 4 contra 2 cm), la tasa de resecabilidad (el 96,1 y el 81,1%), el intervalo libre de enfermedad (25 y 11 meses) y la supervivencia actuarial a 1, 3 y 5 anos (el 93, el 67 y el 36% contra el 78, el 26 y el 12%). Sin embargo, no hemos encontrado diferencias en cuanto a la morbilidad y la mortalidad postoperatorias, que fueron del 28,8 y el 0%, respectivamente, en el grupo C y del 22,6 y el 1,8% en el grupo QT+C. Conclusiones La quimioterapia neoadyuvante no tuvo relacion con mayor morbimortalidad postoperatoria tras la reseccion de metastasis hepaticas de origen colorrectal, pero la supervivencia general a largo plazo en el grupo de pacientes que recibieron este tratamiento fue inferior a la del grupo de pacientes considerados inicialmente resecables.