31 resultados para 321006 Gastroenterology and Hepatology

em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo


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Background and Aim: The identification of gastric carcinomas (GC) has traditionally been based on histomorphology. Recently, DNA microarrays have successfully been used to identify tumors through clustering of the expression profiles. Random forest clustering is widely used for tissue microarrays and other immunohistochemical data, because it handles highly-skewed tumor marker expressions well, and weighs the contribution of each marker according to its relatedness with other tumor markers. In the present study, we e identified biologically- and clinically-meaningful groups of GC by hierarchical clustering analysis of immunohistochemical protein expression. Methods: We selected 28 proteins (p16, p27, p21, cyclin D1, cyclin A, cyclin B1, pRb, p53, c-met, c-erbB-2, vascular endothelial growth factor, transforming growth factor [TGF]-beta I, TGF-beta II, MutS homolog-2, bcl-2, bax, bak, bcl-x, adenomatous polyposis coli, clathrin, E-cadherin, beta-catenin, mucin (MUC) 1, MUC2, MUC5AC, MUC6, matrix metalloproteinase [ MMP]-2, and MMP-9) to be investigated by immunohistochemistry in 482 GC. The analyses of the data were done using a random forest-clustering method. Results: Proteins related to cell cycle, growth factor, cell motility, cell adhesion, apoptosis, and matrix remodeling were highly expressed in GC. We identified protein expressions associated with poor survival in diffuse-type GC. Conclusions: Based on the expression analysis of 28 proteins, we identified two groups of GC that could not be explained by any clinicopathological variables, and a subgroup of long-surviving diffuse-type GC patients with a distinct molecular profile. These results provide not only a new molecular basis for understanding the biological properties of GC, but also better prediction of survival than the classic pathological grouping.

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Over the last few decades, informal caregivers of patients with chronic diseases have received more attention, and there is a growing volume of studies demonstrating high rates of burden, stress, and mental disorders in this group of individuals. The objective of this study was to evaluate the burden, stress, and psychosocial characteristics of informal caregivers of liver transplantation candidates. Participants were assessed by individual evaluations with the following instruments: a semi-structured interview, the Caregiver Burden Scale, the Inventario de Sintomas de Stress para Adultos de Lipp, and the Beck Depression Inventory. The Mann-Whitney test was used for statistical analysis with a significance level of 0.05. The characteristics of the study group (n = 61) were similar to those of groups in other studies with respect to gender (82% were women), kinship (64% were spouses), and age (the mean age was 47.6 years). The main stressors identified by the participants were as follows: doubts about ways to react in a crisis or in emergency situations (42.6%), mood swings of the patient (29.5%), and care involving food and medications (27.9%). Approximately 25% of the caregivers reported that they felt unprepared to adequately perform their roles. Data analysis indicated a greater burden overall on caregivers when the patient`s Model for End-Stage Liver Disease score was greater than or equal to 15 points (P = 0.041). Furthermore, caregivers of patients with alcoholic liver disease showed higher depression (P = 0.034) and overall burden scores (P = 0.031) versus caregivers of patients with liver disease due to other etiologies. In conclusion, the participants showed significantly high levels of burden, stress, and depression. Support measures and caregiver preparation should be implemented by health care providers. Liver Transpl 16: 1164-1168, 2010. (C) 2010 AASLD.

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Background: Patients with Crohn's disease (CD) have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to motility disorders to some degree. Then, we propose to investigate whether gastric emptying of solids in patients with inactive CD is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive CD. Methods: Twenty-six patients with inactive Crohn's disease, as defined by a Crohn's Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using C-13 octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients with scores >= 6 were considered to have dyspepsia. The control group was composed by 19 age-and sex-matched healthy volunteers. Results: Patients with CD had a significantly longer t 1/2 and t lag (p<0.05) than the controls. CD patients with dyspepsia had significantly (p<0.05) prolonged gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. Conclusion: Delayed gastric emptying in inactive Crohn's disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction.

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BACKGROUND & AIMS: Homozygous loss of function mutations in interleukin-10 (IL10) and interleukin-10 receptors (IL10R) cause severe infantile (very early onset) inflammatory bowel disease (IBD). Allogeneic hematopoietic stem cell transplantation (HSCT) was reported to induce sustained remission in 1 patient with IL-10R deficiency. We investigated heterogeneity among patients with very early onset IBD, its mechanisms, and the use of allogeneic HSCT to treat this disorder. METHODS: We analyzed 66 patients with early onset IBD (younger than 5 years of age) for mutations in the genes encoding IL-10, IL-10R1, and IL-10R2. IL-10R deficiency was confirmed by functional assays on patients' peripheral blood mononuclear cells (immunoblot and enzyme-linked immunosorbent assay analyses). We assessed the therapeutic effects of standardized allogeneic HSCT. RESULTS: Using a candidate gene sequencing approach, we identified 16 patients with IL-10 or IL-10R deficiency: 3 patients had mutations in IL-10, 5 had mutations in IL-10R1, and 8 had mutations in IL-10R2. Refractory colitis became manifest in all patients within the first 3 months of life and was associated with perianal disease (16 of 16 patients). Extraintestinal symptoms included folliculitis (11 of 16) and arthritis (4 of 16). Allogeneic HSCT was performed in 5 patients and induced sustained clinical remission with a median follow-up time of 2 years. In vitro experiments confirmed reconstitution of IL-10R-mediated signaling in all patients who received the transplant. CONCLUSIONS: We identified loss of function mutations in IL-10 and IL-10R in patients with very early onset IBD. These findings indicate that infantile IBD patients with perianal disease should be screened for IL-10 and IL-10R deficiency and that allogeneic HSCT can induce remission in those with IL-10R deficiency.

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Background. Transforming growth factor alpha (TGF alpha) is an important mitogen that binds to epidermal growth factor receptor and is associated with the development of several tumors. Aims. Assessment of the immunoexpression of TGF alpha in hepatocellular carcinoma (HCC) and in non-neoplastic liver tissue and its relationship to morphological patterns of HCC. Material and methods. The immunohistochemical expression of TGF alpha was studied in 47 cases of HCC (27 multinodular, 20 nodular lesions). Five lesions measured up to 5 cm and 15 lesions above 5 cm. Thirty-two cases were graded as I or II and 15 as III or IV. The non-neoplastic tissue was examined in 40 cases, of which 22 had cirrhosis. HBsAg and anti-HCV were positive in 5/38 and 15/37 patients, respectively. The statistical analysis for possible association of immunostaining of TGF alpha and pathological features was performed through chi-square test. Results. TGF alpha was detected in 31.9% of the HCC and in 42.5% of the non-neoplastic. There was a statistically significant association between the expression of TGF alpha and cirrhosis (OR = 8.75, 95% CI = [1.93, 39.75]). The TGF alpha was detected more frequently in patients anti-HCV(+) than in those HBsAg(+). The immunoexpression of TGF alpha was not found related to tumor size or differentiation. In conclusion the TGF alpha is present in hepatocarcinogenesis in HBV negative patients. Further analysis is needed to examine the involvement of TGF alpha in the carcinogenesis associated with HCV and other possible agents. In addition, TGF alpha has an higher expression in hepatocyte regeneration and proliferation in cirrhotic livers than in HCC.

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Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

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Background: Cytotoxic T lymphocyte-associated factor 4 (CTLA-4) functions as a negative regulator of T cell-mediated immune response. Molecular changes associated to CTLA-4 gene polymorphisms could reduce its ability to suppress and control lymphocyte proliferation. Aims: To evaluate the frequency of CTLA-4 gene polymorphisms in chronic hepatitis C virus (HCV) infected patients and correlate to clinical and histological findings. Methods: We evaluated 112 HCV-infected subjects prospectively selected and 183 healthy controls. Clinical and liver histological data were analysed. - 318C > T, A49G and CT60 CTLA-4 single-nucleotide polymorphisms (SNPs) were studied by PCR-RFLP and AT(n) polymorphism by DNA fragment analysis by capillary electrophoresis in automatic sequencer. Results: Eight AT repetitions in 3' UTR region were more frequent in HCV-infected subjects. We found a positive association of -318C and + 49G with HCV genotype 3 (P = 0.008, OR 9.13, P = 0.004, OR 2.49 respectively) and an inverse association of both alleles with HCV genotype 1 (P = 0.020, OR 0.19, P = 0.002, OR 0.38 respectively). Allele + 49G was also associated to aminotransferases quotients > 3 (qALT, P = 0.034, qAST, P = 0.041). Allele G of CT60 SNP was also associated with qAST > 3 (P = 0.012). Increased number of AT repetitions was positively associated to severe necroinflammatory activity scores in liver biopsies (P = 0.045, OR 4.62). Conclusion: CTLA-4 gene polymorphisms were associated to HCVinfection. Eight AT repetitions were more prevalent in HCV-infected subjects. - 318C and + 49G alleles were associated to genotypes 1 and 3 infections and increased number of AT repetitions in 3' UTR region favoured severe necroinflammatory activity scores in liver biopsies.

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Background: Urinary copper excretion higher than 100 mu g/24 h is useful for diagnosing Wilson's disease. D-Penicillamine challenge test may produce higher levels than 1400 mu g/24 h, allowing for better diagnostic accuracy. This study investigated whether heterozygotes reach this value and compared copper serum levels, ceruloplasmin, and urinary copper excretion before and after administering D-penicillamine to the parents of Wilson's disease patients. Methods: Fifty parents of adult patients were enrolled to obtain copper serum levels and ceruloplasmin along with 24-h urinary copper excretion before and after administering 1 g D-penicillamine. Results: Serum ceruloplasmin and copper levels were significantly lower in fathers than in mothers (mean 21.8 x 27.8 mg%; 71.4 x 88.0 mu g%; p <= 0.001). The mean of basal 24-h urinary copper excretion was higher in fathers (26.2 x 18.7 mu g/24 h, p = 0.01), but did not differ between the genders after D-penicillamine (521.7 x 525.3, range 31.6-1085.1 mu g/24 h, p = 0.8). Conclusions: The mean values of serum copper, ceruloplasmin, and basal urinary copper excretion were different between males and females. The current diagnostic threshold of 24-h urinary copper excretion after D-penicillamine was not reached by heterozygotes. The increased urinary copper excretion after D-penicillamine challenge was much higher than fivefold the upper limit of normal urinary copper excretion in the majority of heterozygotes and should not be taken into account when diagnosing Wilson's disease. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

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Steatotic livers show increased hepatic damage and impaired regeneration after partial hepatectomy (PH) under ischemia/reperfusion (I/R), which is commonly applied in clinical practice to reduce bleeding. The known function of retinol-binding protein 4 (RBP4) is to transport retinol in the circulation. We examined whether modulating RBP4 and/or retinol could protect steatotic and nonsteatotic livers in the setting of PH under I/R. Steatotic and nonsteatotic livers from Zucker rats were subjected to PH (70%) with 60 minutes of ischemia. RBP4 and retinol levels were measured and altered pharmacologically, and their effects on hepatic damage and regeneration were studied after reperfusion. Decreased RBP4 levels were observed in both liver types, whereas retinol levels were reduced only in steatotic livers. RBP4 administration exacerbated the negative consequences of liver surgery with respect to damage and liver regeneration in both liver types. RBP4 affected the mobilization of retinol from steatotic livers, and this revealed actions of RBP4 independent of simple retinol transport. The injurious effects of RBP4 were not due to changes in retinol levels. Treatment with retinol was effective only for steatotic livers. Indeed, retinol increased hepatic injury and impaired liver regeneration in nonsteatotic livers. In steatotic livers, retinol reduced damage and improved regeneration after surgery. These benefits of retinol were associated with a reduced accumulation of hepatocellular fat. Thus, strategies based on modulating RBP4 could be ineffective and possibly even harmful in both liver types in the setting of PH under I/R. In terms of clinical applications, a retinol pretreatment might open new avenues for liver surgery that specifically benefit the steatotic liver. Liver Transpl 18:1198-1208, 2012. (c) 2012 AASLD.

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In published studies, it has been suggested that dental wear is associated with gastroesophageal reflux disease (GERD). This systematic review was carried out to evaluate the association of GERD, dental erosion, and halitosis and to compare the indices adopted in epidemiological surveys. The Medline database (until October, 2011) was searched systematically to identify studies evaluating the prevalence of oral alterations, such as dental erosion and halitosis, in patients with GERD symptoms. Two reviewers analyzed all reports and the selected studies were evaluated according to the quality of evidence, using the validated Newcastle–Ottawa Quality Assessment Scale. Full-text copies of a total of 32 publications were obtained in duplicate. Sixteen publications were identified among the citations in the Bibliographic lists of studies that fulfilled the exclusion/inclusion criteria and quality of evidence. The relationship between dental erosion and GERD patients was significant in only seven studies. According to three studies, halitosis could be one of several extraesophageal symptoms or manifestations in GERD patients. In one study, it was found that the mucosa of GERD patients was significantly more acidic in comparison with that of the control group. This systematic review showed that there is a relationship between GERD and oral diseases (dental erosion and halitosis). The epidemiological surveys used different indices to analyze GERD and dental erosion. Further research could investigate the best method for assessing the two diseases.

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Objective The influence of choledochoduodenostomy and choledochojejunostomy on the repair of hepatic lesions secondary to biliary obstruction is not well known. The aim of the present study was to compare the effects of choledochoduodenostomy and choledochojejunostomy on the recovery of these lesions in rats with biliary obstruction. Methods Rats subjected to 4 weeks of biliary obstruction underwent choledochoduodenostomy (n=10) or choledochojejunostomy (n=10). The following variables were measured: total bilirubin, alkaline phosphatase, aminotransferases, and albumin. Hepatic mitochondrial energy metabolism was evaluated by calculating the respiratory control ratio and the oxidative phosphorylation index. Hepatic morphometry was used to estimate the mass of the hepatocytes, bile ducts, and fibrosis, as well as the hepatic stellate cell count. Results After choledochoduodenostomy and choledochojejunostomy, there was a regression in cholestasis and a reduction in the oxidative phosphorylation index. However, the total bilirubin, alkaline phosphatase, albumin, and respiratory control ratio values improved only after choledochojejunostomy. The mass of the liver, spleen, and fibrosis was reduced after both choledochoduodenostomy and choledochojejunostomy, but the number of hepatic stellate cells increased. After choledochojejunostomy, the hepatic mass recovered completely, and the spleen mass was significantly reduced compared with that after choledochoduodenostomy. After both choledochoduodenostomy and choledochojejunostomy, enterobiliary reflux, biliary contamination, and an exacerbation in hepatic inflammation developed. Conclusion Choledochojejunostomy was more effective than choledochoduodenostomy, but both techniques induced enterobiliary reflux and biliary contamination, which may explain the maintenance of hepatic alterations, especially after choledochoduodenostomy. Eur J Gastroenterol Hepatol 24: 1039-1050 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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Schwannoma is a tumor derived from Schwann cells which usually arises in the upper extremities, trunk, head and neck, retroperitoneum, mediastinum, pelvis, and peritoneum. However, it can arise in the gastrointestinal tract, including biliary tract. We present a 24-year-old male patient with obstructive jaundice, whose investigation with computed tomography abdomen showed focal wall thickening in the common hepatic duct, difficult to differentiate with hilar adenocarcinoma. He was diagnosed intraoperatively schwannoma of common bile duct and treated with local resection. The patient recovered well without signs of recurrence of the lesion after 12 mo. We also reviewed the common bile duct schwannoma related in the literature and evaluated the difficulty in pre and intraoperative differential diagnosis with adenocarcinoma hilar. Resection is the treatment of choice for such cases and the tumor did not recur in any of the resected cases. (C) 2012 Baishideng. All rights reserved.

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AIM: To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system abnormalities such as altered motility. METHODS: The study examined the distribution of the P2X(2) receptor (P2X(2)R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X(2)R with neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice. In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm(2)) and area profile (mu m(2)) of P2X(2)R-positive neurons. In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NADH) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and area. RESULTS: In the present study, we observed a 29.6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG). In addition, the average small intestine area was increased by approximately 29.6% in the OG compared to the CG. Immunoreactivity (IR) for the P2X(2)R, nNOS, ChAT and CaIR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups. This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes. P2X(2)R-IR was observed to co-localize 100% with that for nNOS, ChAT and CaIR in neurons of both groups. In the ob/ob group, however, we observed that the neuronal density (neuron/cm(2)) of P2X(2)R-IR cells was increased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice. The neuronal density of CaIR-IR neurons was not different between the groups. Morphometric studies further demonstrated that the cell body profile area (mu m(2)) of nNOS-IR, ChAT-IR and CaIR-IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls. Staining for NADH diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NADH-diaphorase positive neurons in the nnyenteric ganglia revealed an overall similarity between the two groups. CONCLUSION: We demonstrate increases in P2X(2)R expression and alterations in nNOS, ChAT and CaIR IR in ileal myenteric neurons of female ob/ob mice compared to wild-type controls. (c) 2012 Baishideng. All rights reserved.

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AIM: To evaluate the results of duodenal stenting for palliation of gastroduodenal malignant obstruction by using a gastric outlet obstruction score (GOOS). METHODS: A prospective, non-randomized study was performed at a tertiary center between August 2005 and April 2010. Patients were eligible if they had malignant gastric outlet obstruction (GOO) and were not candidates for surgical treatment. Medical history and patient demographics were collected at baseline. Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180 d later or unscheduled as necessary. RESULTS: Fifteen patients (6 male, 9 female; median age 61 years) with GOO who had undergone duodenal stenting were evaluated. Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral intake (93.33%), including 7 patients who were using a feeding tube. Laboratory data showed biliary obstruction in eight cases (53.33%); all were submitted to biliary drainage. Two patients developed obstructive symptoms due to tumor ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of stent migration occurred. A good response to treatment was observed, with a mean time of approximately 1 d (19 h) until toleration of a liquid diet and slightly more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h). The mean time to first failure to maintain liquid intake (GODS >= 1) was 93 d. During follow-up, the mean time to first failure to maintain the previously achieved GODS of 2-3 (solid/semi-solid food), considered technical failure, was 71 d. On the basis of oral intake a GODS is defined: 0 for no oral intake; 1 for liquids only; 2 for soft solids only; 3 for low-residue or full diet. CONCLUSION: Enteral stenting to alleviate gastroduodenal malignant obstruction improves quality of life in patients with limited life expectancy, which can be evaluated by using a GOO scoring system. (C) 2012 Baishideng. All rights reserved.