Salvage abdominoperineal resection for anal cancer following chemoradiation: a proposed scoring system for predicting postoperative survival.

BACKGROUND AND OBJECTIVES: Anal carcinoma is treated primarily by chemoradiation. Failure of this treatment requires salvage surgery. The aims of this retrospective study were to assess the survival probability after rescue surgery and design a pathological risk score (PRS) to predict postoperative outcome. METHODS: From 1982 to 2011, the clinical and pathological data of 111 patients treated with chemoradiation or radiation alone and abdominoperineal resection were reviewed. The Kaplan-Meier method was used to assess overall survival and parametric modeling was applied to determine prognostic factors and design a PRS. RESULTS: The 2- and 5-year overall survival rates were 60% and 24.5%, respectively. The multivariate analysis showed that nodal disease (P < 0.03), resection margin (P < 0.001), and perineural and/or lymphovascular invasion (P < 0.0001) were significantly associated with survival. Patients who presented negative values for these three variables were estimated to show a 5-year survival rate of 55% compared with 0.03% for patients who presented positive values. CONCLUSIONS: Positive surgical margin, the presence of perineural and/or lymphovascular invasion and positive nodal involvement were identified as significant independent predictors of mortality. The PRS was shown to be highly predictive of postoperative outcome.

A pilot study to evaluate the safety, tolerance, and efficacy of a novel stationary antral balloon (SAB) for obesity.

BACKGROUND: A 150 cm pear-shaped gastric balloon with a 30 cm-long duodenal stem and a 7 g metallic weight at its distal end was designed and developed to facilitate weight loss by (a) delaying gastric emptying thus enhancing interprandial satiety, and (b) stimulating antral and duodenal receptors of satiation. METHODS: Twenty-six patients (body mass index of 29 to 40 kg/m) who failed to lose weight despite dietary intervention underwent endoscopic implantation of the balloon device. Patients were monitored for tolerance to the balloon, complications, weight loss, and compliance with a restricted caloric intake. RESULTS: Six men and 20 women with a median body weight of 93.0 kg (range, 73.5 to 119.9), median body mass index 34.3 kg/m (range, 28.8 to 39.5) underwent balloon implantation for a median period of 4.0 months (range, 0.75 to 6.0). Twenty-two patients successfully complied with a 1250 to 1500 kcal daily diet restriction during the study period. Median weight reduction was 6.5 kg (range, 3.7 to 19.9). Patients with initial body weight of >90 kg tended to loose more weight (8.1 kg) than patients weighing <90 kg (4.5 kg) (P=0.14). Nine patients with dwell times of 6 months lost 11.5+/-4.6 kg. The balloon malfunctioned in 4 patients (in 1 patient, the balloon leaked spontaneously but remained in the stomach and in 3 patients, the balloon migrated distally). CONCLUSIONS: Our novel balloon device may be effective in inducing weight loss by promoting compliance with a restricted caloric intake and is well tolerated due to its small size. Complications resulted from balloon rupture, which can be easily prevented by enhancements in design and use of alternative materials.

Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non alcoholic fatty liver disease in rats.

AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition of lipid peroxidation and the effect of oral SNAC administration in the prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model. METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4 wk. SNAC-treated animals (n=6) (1.4 mg/kg per day of SNAC, orally) were compared to 2 control groups: one (n=6) received PBS solution and the other (n=6) received NAC solution (7 mg/kg per day). Histological variables were semiquantitated with respect to macro and microvacuolar fat changes, its zonal distribution, foci of necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal distribution. LOOHs from samples of liver homogenates were quantified by HPLC. Nitrate levels in plasma of portal vein were assessed by chemiluminescence. Aqueous low-density lipoprotein (LDL) suspensions (200 microg protein/mL) were incubated with CuCl(2) (300 micromol/L) in the absence and presence of SNAC (300 micromol/L) for 15 h at 37 degree Celsius. Extent of LDL oxidation was assessed by fluorimetry. Linoleic acid (LA) (18.8 micromol/L) oxidation was induced by soybean lipoxygenase (SLO) (0.056 micromol/L) at 37 degree Celsius in the presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 micromol/L) and monitored at 234 nm. RESULTS: Animals in the control group developed moderate macro and microvesicular fatty changes in periportal area. SNAC-treated animals displayed only discrete histological alterations with absence of fatty changes and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated group was positively correlated with a decrease in the concentration of LOOH in liver homogenate, compared to the control group (0.7+/-0.2 nmol/mg vs 3.2+/-0.4 nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases were unaltered. The ability of SNAC in preventing lipid peroxidation was confirmed in in vitro experiments using LA and LDL as model substrates. CONCLUSION: Oral administration of SNAC prevents the onset of NAFLD in Wistar rats fed with choline-deficient diet. This effect is correlated with the ability of SNAC to block the propagation of lipid peroxidation in vitro and in vitro.

Ursodeoxycholic acid ameliorates experimental ileitis counteracting intestinal barrier dysfunction and oxidative stress.

The aim of this study was to evaluate the effect of ursodeoxycholic acid (UDCA) on intestinal permeability (IP) and reactive oxygen species (ROS) generation in indomethacin-induced enteropathy, a well-known experimental model of Crohn's disease. Seventy-eight male Wistar rats were randomly assigned to receive indomethacin, indomethacin + UDCA, or vehicles. Indomethacin induced a significant increase in the fraction of urinary excretion of 51Cr-EDTA following oral administration (7.9 +/- 1.3 vs 2.3 +/- 0.2%; P < 0.05) and lucigenin-amplified chemiluminescence in intestinal fragments ex vivo (10.1 +/- 1.9 vs 2.6 +/- 0.4 cpm x 10(3)/mg; P < 0.05) compared to controls. UDCA significantly reversed these effects (P < 0.05), without being incorporated in biliary bile acid composition (HPLC analysis). These findings support a local protective effect of UDCA in experimental ileitis by the modulation of intestinal barrier dysfunction and oxidative stress. In short, they provide insights into mechanisms of action of UDCA in intestinal inflammation and a new perspective on the treatment of Crohn's disease.

Vitamin C and vitamin E in prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in choline deficient diet fed rats.

AIM: Oxidative stress has been implicated in the pathogenesis of Nonalcoholic Fatty Liver Disease (NAFLD). Vitamin C and vitamin E are known to react with reactive oxygen species (ROS) blocking the propagation of radical reactions in a wide range of oxidative stress situations. The potential therapeutic efficacy of antioxidants in NAFLD is unknown. The aim of this study was to evaluate the role of antioxidant drugs (vitamin C or vitamin E) in its prevention. METHODS: Fatty liver disease was induced in Wistar rats by choline-deficient diet for four weeks. The rats were randomly assigned to receive vitamin E (n = 6) - (200 mg/day), vitamin C (n = 6) (30 mg/Kg/day) or vehicle orally. RESULTS: In the vehicle and vitamin E-treated rats, there were moderate macro and microvesicular fatty changes in periportal area without inflammatory infiltrate or fibrosis. Scharlach stain that used for a more precise identification of fatty change was strong positive. With vitamin C, there was marked decrease in histological alterations. Essentially, there was no liver steatosis, only hepatocellular ballooning. Scharlach stain was negative. The lucigenin-enhanced luminescence was reduced with vitamin C (1080 +/- 330 cpm/mg/min x 10(3)) as compared to those Vitamin E and control (2247 +/- 790; 2020 +/- 407 cpm/mg/min x 10(3), respectively) (p < 0.05). Serum levels of aminotransferases were unaltered by vitamin C or vitamin E. CONCLUSIONS: 1) Vitamin C reduced oxidative stress and markedly inhibited the development of experimental liver steatosis induced by choline-deficient diet; 2)Vitamin E neither prevented the development of fatty liver nor reduced the oxidative stress in this model.

Protective effect of ascorbic acid in experimental gastric cancer: reduction of oxidative stress.

AIM: Oxidative stress participates in the cell carcinogenesis by inducing DNA mutations. Our aim was to assess whether ascorbic acid, an antioxidant, could have a role in preventing ROS (Reactive Oxygen Species) generation in experimental gastric carcinoma in a rat model. METHODS: Experimental gastric cancer was induced in twelve Wistar male rats (weighting 250-350 g) by profound duodeno-gastric reflux throught split gastrojenunostomy. The rats were allocated to the following groups: Group I (n=6) was the control; Group II (n=6) which was mantained with daily intake of tape water with Vitamin C (30 mg/Kg). After 6 or 12 months, samples of gastric tumor or non tumor mucosa were taken from the anastomosis of both groups. Oxidative stress was measured by superoxide quantification through lucigenin-amplified chemiluminescence base and by staining with Nitrobluetetrazolium. The histopathologic confirmation of adenocarcinoma was made by eosin-hemathoxilin method. RESULTS: The intestinal type of gastric adenocarcinoma was microscopically identified in all animals of group I whereas only 3 rats of group II showed an adenocarcinoma without macroscopic evidence of them. The cancers were located in the anastomosis in all cases. Basal luminescence from tumor gastric tissue generated 38.4+/-6.8 count per minute/mg/X10(6) (mean+/-SD) and 14.9+/-4.0 count per minute/mg/X10(6), respectively, in group I and II animals (P<0.05). The Nitrobluetetrazolium method showed intense staining in tumor tissues but not in non neoplasic mucosa. CONCLUSION: Experimental gastric tumors seem to produce more reactive oxygen species than non neoplasic gastric tissue. The reduction of oxidative stress and gastric tumor incidence in rats were induced by the intake of ascorbic acid. Therefore, it may have a role in the prevention of gastric carcinoma.