Preoperative risk factors for early hemorrhagic complications in bariatric surgery: a case-control study.

BACKGROUND: Although a reliable procedure in morbid obesity treatment, bariatric surgery may be associated with serious complications such as leakage or bleeding. We aimed to analyze the preoperative factors involved in patients with early postoperative hemorrhage after any type of bariatric surgery who required conservative treatment or reoperation for this complication. METHODS: Retrospective case-controlled study (1:3) of 2 patient cohorts (postoperative bleeding/controls) matched by type of surgical intervention. RESULTS: Hypertension (Odds Ratio 5.029; 95% Confidence Interval 1.78-14.13) and history of antiplatelet medication (OR 13.263; 95% CI 1.39-125.9) were independent risk factors in the bivariate analyses, confirmed in the logistic regression model on multivariate analysis. CONCLUSIONS: With no between-group differences in Body Mass Index (BMI) and type 2 Diabetes (T2D), early hemorrhagic complications were found to be more frequent in patients with hypertension or antiplatelet drug treatment.

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.

[Recommendations for the peri-operative management of bariatric surgery patients: results of a national survey]. / Recomendaciones para el manejo perioperatorio de los pacientes de cirugía bariátrica: resultados de una encuesta nacional.

To standardise possible peri-operative bariatric surgery protocols, a survey was prepared to be filled in by members of the Spanish Society for Obesity (Sociedad Española de Cirugía de la Obesidad) (SECO), and to approve it at the XII National Congress. A total of 47 members of SECO from 14 autonomous communities responded, and it unanimously approved by the Congress. As highly recommended peri-operative procedures, were proposed: full laboratory analysis (98%) with an endocrine study (90%), ECG (96%), chest x-ray (98%), an oesophageal-gastric imaging test (endoscopy or gastro-duodenal transit study (98%), antibiotic prophylaxis (92%) and use of low molecular weight heparins pre-operatively (96%), and for 2 weeks (83%). Pre-surgical, abdominal ultrasound (86%), spirometry (80%), diet (88%) and psychological study (76%), and during surgery, use of elastic stockings (76%), leak tests (92%) and drainages (90%), were established as advisable procedures.

Intraoperative real-time (99m)Tc-sestamibi scintigraphy with miniature gamma camera allows minimally invasive parathyroidectomy without ioPTH determination in primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) is being widely accepted as the procedure of choice for the treatment of primary hyperparathyroidism (PHPT), which is caused by a parathyroid single adenoma in more than 80% of cases in some series. Preoperative location studies, like sestamibi scans, allow the proper identification of pathologic gland and intraoperative parathormone (ioPTH) assay is used to confirm the removal of the adenoma. We have studied the feasibility of a new miniature gamma camera (MGC) used intraoperatively to locate parathyroid adenomas and confirm its correct excision. MATERIALS AND METHODS: Twenty patients with PHPT positively diagnosed by preoperative sestamibi scans underwent a MIP. In the first five patients, both ioPTH assay and the new hand-held MGC were used consecutively to locate and confirm the excision of the pathologic gland. For the next 15 cases, PTH was measured but not used intraoperatively for diagnosis and the MGC was the only diagnostic tool employed to perform the operation. Concordance between preoperative and intraoperative scintigraphy, surgical time, success rate, and complications are analyzed. RESULTS: All cases were operated on successfully by a MIP. After 1 year follow-up, the drop of PTH and the normalization of calcium levels confirmed the excision of all pathologic tissue. The MGC proved its usefulness in all patients offering accurate real-time intraoperative images for location and confirming the success of the procedure. CONCLUSIONS: The MGC is a useful instrument in MIP for PHPT. It may be used as complementary to the standard tools used to date, or even replace them, at least in selected cases of single adenomas.

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.

Preoperative inspiratory muscular training to prevent postoperative hypoxemia in morbidly obese patients undergoing laparoscopic bariatric surgery. A randomized clinical trial.

BACKGROUND: Morbidly obese patients show an increased risk of postoperative hypoxemia and pulmonary complications when compared with normal weight subjects. The purpose of this study was to determine the effects of preoperative inspiratory muscular training (IMT) on postoperative arterial oxygenation in morbidly obese patients submitted to laparoscopic bariatric surgery. METHODS: Forty-four morbidly obese patients were randomly assigned to receive either preoperative usual care (control group, n = 21) or preoperative IMT (trained group, n = 23) for a month prior to the date of surgery. Data on oxygenation (PaO2/FiO2 ratio) were obtained at 1 h and at 12 h after surgery (PACU 1 h and PACU 12 h, respectively). Data on maximum static inspiratory pressure (MIP) were obtained before and after the training period, and at postanesthesia care unit (PACU) 12-h time point. RESULTS: PaO2/FiO2 was significantly higher in the trained group than in the control group, both at PACU 1 h (305.2 ± 77.6 vs. 248.8 ± 53.8, P = 0.008) and at PACU 12 h (333.5 ± 59.6 vs. 289.7 ± 79.6, P = 0.044). As a consequence, the percentage of patients with relative hypoxemia (PaO2/FiO2 lower than 300 mmHg) at the time of PACU discharge was higher in the control group (57 vs. 17 %, P: 0.006). MIP was significantly higher in the trained group compared with the control group at the preoperative time point (89.87 ± 19.00 vs. 77.00 ± 21.20 cm H2O, P = 0.04). CONCLUSIONS: Preoperative IMT improved postoperative oxygenation and increased inspiratory muscular strength in morbidly obese patients submitted to laparoscopic bariatric surgery.

Anatomical basis for the low incidence of internal hernia after a laparoscopic Roux-en-Y gastric bypass without mesenteric closure.

BACKGROUND: Different techniques have been designed to reduce the rate of internal hernia (IH) after laparoscopic bariatric surgery, and mesenteric closure is possibly the most controversial. We propose a laparoscopic Roux-en-Y gastric bypass (LRYGB) procedure without mesenteric closure with several specific technical details to avoid IH. To support this view, we have reviewed the outcome of our LRYGB patients and have carried out an anatomical study on cadavers. METHODS: A retrospective observational study was carried out using the Unit's prospective database. The patients selected were those who were operated on for morbid obesity using LRYGB and who presented to the Emergency Unit with symptoms of intestinal obstruction (IO). Data concerning demographics, weight progress, technical details of the surgery, follow-up percentage, morbidity, and mortality were collected. Furthermore, an anatomical model was made in order to recreate the surgery on cadavers. RESULTS: Only 1.6 % of postoperative IO and very few (0.3 %) of IH cases were associated with our technique of LRYGB without mesenteric closure. The anatomical model showed two large potential hernia spaces, but their supramesocolic situation, the orientation of the bowel loops, leaving the mesentery and omentum undivided and the antecolic passage of the alimentary limb made intestinal herniation difficult even though the mesenteric spaces were not closed. CONCLUSIONS: With a proper technique, the closure of mesenteric spaces after a LRYGB is not essential to avoid postoperative IH in bariatric patients, as evidenced in an anatomical model.

Radiotherapeutic management of the chyloperitoneum following abdominal aortic aneurysm repair.

Chyloperitoneum is a rare but life-threatening complication with no uniformity concerning the treatment. We present a 77-year-old male with chylous ascites after open abdominal aneurysmectomy refractory to conservative and surgical strategies. After failure of re-exploration with periaortic lymphatic cauterization and drainage, he was treated with five cycles of retroperitoneal radiotherapy. At 12 months of follow-up, the patient remains asymptomatic without any objective evidence of chyloperitoneum relapse. Periaortic radiotherapy may be a feasible alternative in the management of the chylous ascites following abdominal aortic aneurysm surgery.

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

OBJECTIVE: 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. DESIGN AND METHODS: In 47 patients with morbid obesity and 45 control subjects, the levels in blood of adipocytokines, cGMP, nitric oxide (NO) metabolites, and atrial natriuretic peptide (ANP) were studied. Whether weight loss after a bariatric surgery reverses the changes in these parameters was evaluated. RESULTS: NO metabolites and leptin increase (and adiponectin decreases) similarly in patients with steatosis or NASH, suggesting that these changes are due to morbid obesity and not to liver disease. Inflammation and cGMP homeostasis are affected both by morbid obesity and by liver disease. The increases in interleukin 6 (IL-6), interleukin 18 (IL-18), plasma cGMP, ANP, and the decrease in cGMP in lymphocytes are stronger in patients with NASH than with steatosis. All these changes reverse completely after bariatric surgery and weight loss, except IL-18. CONCLUSION: Altered cGMP homeostasis seems to contribute more than inflammation to changes in leptin and adiponectin in morbid obesity.

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/m(2), which had decreased at the moment of survey to 31.7 ± 5.4 kg/m(2). 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.

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.

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.

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.

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.

['Same-day' thyroid surgery. Results after 805 thyroidectomies in a fast-track program]. / Cirugía tiroidea con menos de 24 horas de hospitalización. Resultados tras 805 tiroidectomías consecutivas en un programa de alta precoz tipo fast-track.

INTRODUCTION: The aim of this study was to analyze the validity of a fast-track surgery program with less than 24-hour admission for all thyroid disease treated in an endocrine surgery unit. MATERIAL AND METHOD: Between January 2000 and January 2006, 805 consecutive patients underwent thyroid surgery in a fast-track program. Data on type of disease, procedure, operating time, length of hospital stay, postoperative morbidity, and the number of reinterventions and readmissions were gathered. RESULTS: After a minimum follow-up of 6 months, transitory hypocalcemia occurred in 4.8%, permanent hypocalcemia in 0.2%, transitory dysphonia in 2.5%, and permanent dysphonia in 1.1%. Only 7 patients required emergency reintervention in the first 6 hours after surgery, in all patients due to hemorrhage. Most of these complications occurred in patients undergoing surgery for hyperthyroidism or in those undergoing total thyroidectomy with modified radical neck dissection. Most patients were discharged within 24 hours with a mean length of hospital stay of 23.9 hours, excluding patients who underwent cervical lymphadenectomy. There were only three readmissions, all of which were due to correction of symptomatic hypocalcemia. CONCLUSIONS: Except for total thyroidectomy with modified radical neck dissection due to cancer, all thyroid surgery can be performed in a fast-track program with less than 24-hour admission, within a specialized endocrine surgery unit.

Potential role of a new hand-held miniature gamma camera in performing minimally invasive parathyroidectomy.

PURPOSE: Sestamibi scans have increased the use of minimally invasive parathyroidectomy (MIP) to treat primary hyperparathyroidism (PHPT) when caused by a parathyroid single adenoma. The greatest concern for surgeons remains the proper identification of pathological glands in a limited surgical field. We have studied the usefulness of a new hand-held miniature gamma camera (MGC) when used intraoperatively to locate parathyroid adenomas. To our knowledge this is the first report published on this subject in the scientific literature. METHODS: Five patients with PHPT secondary to a single adenoma, positively diagnosed by preoperative sestamibi scans, underwent a MIP. A gamma probe for radioguided surgery and the new hand-held MGC were used consecutively to locate the pathological glands. This new MGC has a module composed of a high-resolution interchangeable collimator and a CsI(Na) scintillating crystal. It has dimensions of around 15 cmx8 cmx9 cm and weighs 1 kg. The intraoperative assay of PTH (ioPTH) was used to confirm the complete resection of pathological tissue. RESULTS: All cases were operated on successfully by a MIP. The ioPTH confirmed the excision of all pathological tissues. The MGC proved its usefulness in all patients, even in a difficult case in which the first attempt with the gamma probe failed. In all cases it offered real-time accurate intraoperative images. CONCLUSION: The hand-held MGC is a useful instrument in MIP for PHPT. It may be used to complement the standard tools used to date, or may even replace them, at least in selected cases of single adenomas.

[Effect of neoadjuvant chemotherapy on the results of resection of colorectal liver metastases]. / Efecto de la quimioterapia neoadyuvante en los resultados de la cirugía de resección de las metástasis hepáticas de origen colorrectal.

INTRODUCTION: Surgery is the treatment of choice in patients with colorectal liver metastases. However, only 10% to 20% of these cases are resectable. The use of neoadjuvant chemotherapy may allow surgery in patients with tumors initially considered unresectable. The aim of this study was to compare the results of liver resection due to colorectal liver metastases in patients with and without neoadjuvant chemotherapy. PATIENTS AND METHOD: We studied 105 patients who underwent surgery for liver metastases from colorectal cancer. The patients were divided into two groups according to treatment: surgery in patients with initially resectable tumors (group 1) and neoadjuvant chemotherapy plus surgery (group 2) in patients with initially irresectable tumors, who were considered for surgery after response to chemotherapy. Age, sex, origin of primary tumor, time of presentation, number, maximum size and location of metastases, CEA, resection margin, postoperative morbidity and mortality, length of hospital stay, recurrence rate, survival and disease-free survival were compared between the 2 groups of patients. RESULTS: When group 1 was compared with group 2, statistically significant differences were observed in synchronicity (30.8% vs 77.4%), bilobarity (13.5% vs 58.5%), number and size of metastases (1 vs 3 nodules and 4 cm vs 2 cm), resectability rate (96.1% vs 81.1%), disease-free interval (25 vs 11 months) and long-term survival at 1, 3 and 5 years (93%, 67% and 36% vs 78%, 26% and 12%). However, no statistically significant differences were found in postoperative morbidity and mortality (28.8% and 0% in group 1 and 22.6% and 1.8% in group 2, respectively). CONCLUSIONS: Neoadjuvant chemotherapy was not associated with greater postoperative morbidity and mortality after resection of colorectal liver metastases, but long-term survival was lower in the group of patients receiving this treatment modality than in those with tumors initially considered resectable.

Circulating TNF-alpha and its soluble receptors during experimental acute pancreatitis.

Clinical and experimental studies have shown increased concentrations of TNF-alpha and its soluble receptors in serum of patients with acute pancreatitis. In this work, we have investigated the time-course of TNF-alpha and its soluble receptors during taurocholate-induced acute pancreatitis. In addition, since TNF-alpha itself could mediate the shedding of its receptors, we have assessed the effect of inhibiting TNF-alpha production on the release of soluble TNF-alpha receptors in experimental acute pancreatitis. Our results indicate that soluble receptors are released in the early stages of the disease and this increase is concomitant with the release of TNF-alpha, which is mainly bound to specific proteins. The increased concentrations of its receptors strongly suggest that they could be these binding proteins. Inhibition of TNF-alpha generation with pentoxifylline abrogated the shedding of sTNF-alphaR1, but had no effect on sTNF-alphaR2. This finding suggests that the shedding of sTNF-alphaR1 is induced by TNF-alpha itself, but in the case of sTNF-alphaR2, the shedding appears to be induced by another mechanism.

Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases.

OBJECTIVE: To assess the effects of inhibiting both tumor necrosis factor (TNF)-alpha production and xanthine oxidase activity on the inflammatory response, mitogen-activated protein kinase (MAPK) activation and mortality in necrotizing acute pancreatitis in rats. SUMMARY BACKGROUND DATA: Pancreatic injury triggers 2 major pathways involved in the systemic effects of severe acute pancreatitis: pro-inflammatory cytokines and oxidative stress. METHODS: Pancreatitis was induced by intraductal infusion of 3.5% sodium taurocholate. We examined whether treatment with oxypurinol, a specific inhibitor of xanthine oxidase, and/or pentoxifylline, an inhibitor of TNF-alpha production, affects pancreatic damage, ascites, lung inflammation, and MAPK phosphorylation. RESULTS: Oxypurinol prevented p38 phosphorylation in the pancreas and partially avoided the rise in lung myeloperoxidase activity. Pentoxifylline prevented erk 1/2 and JNK phosphorylation in the pancreas, and it partially reduced ascites and the rise in lung myeloperoxidase activity. Combined treatment with oxypurinol and pentoxifylline almost completely abolished ascites, MAPK phosphorylation in the pancreas, and the increase in lung myeloperoxidase activity. Histology revealed a reduction in pancreatic and lung damage. These changes were associated with a significant improvement of survival. CONCLUSIONS: : Simultaneous inhibition of TNF-alpha production and xanthine oxidase activity greatly reduced local and systemic inflammatory response in acute pancreatitis and decreased mortality rate. These effects were associated with blockade of the 3 major MAPKs.