Low Incidence of Advanced Neoplasia in Serrated Polyposis Syndrome After (Sub)total Colectomy: Results of a 5-Year International Prospective Cohort Study.

INTRODUCTION: Serrated polyposis syndrome (SPS) is accompanied by a substantially increased colorectal cancer (CRC) risk. To prevent or treat CRC in patients with a very high polyp burden, (sub)total colectomy with ileorectal or ileosigmoidal anastomosis is regularly performed. The CRC risk after (sub)total colectomy might be decreased, but evidence is lacking. We aimed to assess the yield of endoscopic surveillance in patients with SPS who underwent (sub)total colectomy. METHODS: For this post hoc analysis, we used prospectively collected data from a large international prospective cohort study. We included patients diagnosed with SPS (World Health Organization type I and/or III) who underwent (sub)total colectomy. Primary endpoint was the cumulative 5-year incidence of CRC and advanced neoplasia (AN). RESULTS: Forty-eight patients (mean age 61 [±7.8]; 52% men) were included and followed up for a median of 4.7 years (interquartile range 4.7-5.1). None of the patients developed CRC during follow-up. Five patients developed AN, corresponding to a cumulative 5-year AN incidence of 13% (95% confidence interval 1.2-23). In 4 patients, AN was diagnosed at the first surveillance endoscopy after study inclusion, and in 1 patient, AN was detected during subsequent rounds of surveillance. The risk of AN was similar for patients with ileorectal and ileosigmoidal anastomosis (logrank P = 0.83). DISCUSSION: (Sub)total colectomy mitigates much of the excess risk of CRC in patients with SPS. Advanced neoplasms are mainly detected at the first endoscopy after (sub)total colectomy. Based on these results, after the first surveillance, intervals might be extended beyond the currently recommended 1-2 years.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Comparison of the long-term outcome of two therapeutic strategies for the management of abdominal abscess complicating Crohn's disease: percutaneous drainage or immediate surgical treatment.

AIM: The management of abdominal abscesses complicating Crohn's disease is complex and involves a difficult choice between medical, radiological and surgical procedures. The long-term outcome was compared for two strategies for the management of abdominal abscess: percutaneous drainage (PD) followed by rescue surgery in the case of failure vs direct immediate surgery (IS). We also compared the results of IS with surgery performed after PD failure. METHODS: We retrospectively identified 44 patients with Crohn's disease with an abdominal abscess from January 2000 to December 2009. Therapeutic success was defined as abscess resolution and no reappearance within 1 year of follow-up. RESULTS: The first therapeutic approach was PD in 22 cases and IS in the other 22 cases. IS had a higher therapeutic success rate than PD (95.5% vs 27.2% respectively; P < 0.001). PD was the only independent variable related to treatment failure in the multivariate analysis after adjustment for possible confounders such as abscess size, multilocularity, presence of fistula and corticosteroid use (OR 88.26, 95% CI 7.38-1055.36; P < 0.001). Surgery after failure of PD (n = 16) was associated with longer total hospitalization (56.12 ± 35.89 vs 27.52 ± 15.11 days; P = 0.017) and longer postoperative stay (44.0 ± 83.7 vs 14.3 ± 30 days; P = 0.179) and needed a second operation more often (5/16, 31% vs 1/22, 4.5%; P = 0.065) than IS. CONCLUSIONS: Percutaneous drainage provided durable abscess resolution in only one-third of the patients compared with more than 90% of those treated with IS. In addition, surgery performed after PD failure results in a poorer outcome than IS.

Genetic polymorphisms in fatty acid metabolism genes and colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included dietary fat intake; consequently, the role of genes in the fatty acid biosynthesis and metabolism pathways is of particular interest. Moreover, hyperlipidaemia has been associated with different type of cancer and serum lipid levels could be affected by genetic factors, including polymorphisms in the lipid metabolism pathway. The aim of this study is to assess the association between single-nucleotide polymorphisms (SNPs) in fatty acid metabolism genes, serum lipid levels, body mass index (BMI) and dietary fat intake and CRC risk; 30 SNPs from 8 candidate genes included in fatty acid biosynthesis and metabolism pathways were genotyped in 1780 CRC cases and 1864 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. Several LIPC (lipase, hepatic) polymorphisms were found to be associated with CRC risk, although no particular haplotype was related to CRC. The SNP rs12299484 showed an association with CRC risk after Bonferroni correction. We replicate the association between the T allele of the LIPC SNP rs1800588 and higher serum high-density lipoprotein levels. Weak associations between selected polymorphism in the LIPC and PPARG genes and BMI were observed. A path analysis based on structural equation modelling showed a direct effect of LIPC gene polymorphisms on colorectal carcinogenesis as well as an indirect effect mediated through serum lipid levels. Genetic polymorphisms in the hepatic lipase gene have a potential role in colorectal carcinogenesis, perhaps though the regulation of serum lipid levels.

Impact of age on recurrence and severity of left colonic diverticulitis.

AIM: There has been controversy about the presentation and treatment of acute colonic diverticulitis (AD) in young patients. The aim of this observational study was to evaluate the virulence and natural history of AD in three different age groups of patients. METHOD: The study was performed on 686 patients with the diagnosis of a first episode of AD admitted between January 1998 and December 2008. Patients were classified into three groups: age 45 years or younger (group 1), 45-70 years of age (group 2) and 70 years or more (group 3). The variables studied were gender, American Society of Anesthesiologists status, associated comorbidity, type of treatment, length of hospital stay and recurrence of AD. RESULTS: Group 1 included 99 (14.4%) patients, group 2 339 (49.4%) and group 3 248 (36.2%). Of these, 144 patients needed emergency operation at the first admission, 25 underwent elective surgery after the first episode of AD and 10 died after medical treatment; 507 patients were followed for recurrence. In all, 104 (20.5%) patients had a recurrence of AD that required hospitalization. Fifty (9.9%) presented with one episode of severe recurrence, without any difference between the groups (P = 0.533). There were no differences in the analysis of cumulative recurrence (Kaplan-Maier) between the three groups. CONCLUSION: AD does not present a more aggressive clinical course in younger patients and it can be safely managed using the same strategy as in middle aged and older patients.

Colorectal cancer screening: strategies to select populations with moderate risk for disease.

OBJECTIVE: to analyse the association between rectal bleeding or a family history of colorectal cancer (CRC) and the results obtained in two rounds of a CRC screening pilot programme performed in L Hospitalet, Barcelona, Spain. SUBJECTS: males and females (50-69 years) were the target population. Together with the invitation letter, they received a questionnaire in which they were asked about rectal bleeding, family history of CRC and related neoplasms. The screening test was a guaiac-based faecal occult blood test (FOBT), and colonoscopy for positive tests. RESULTS: 25,829 FOBT were performed in 18,405 individuals. Information on rectal bleeding and a family history of CRC were obtained for 9,849 and 9,865 cases, respectively. Male sex (OR = 1.32), 60-69 years of age (OR = 1.48), rectal bleeding (OR = 1.84) and history of CRC (OR = 1.54) were independent predictors of positive FOBT. With regard to colonoscopy, a greater risk of diagnosing advanced neoplasm was observed among men (OR = 2.47) and subjects with a family history of CRC (OR = 1.98). CONCLUSIONS: CRC screening programmes must have instruments that make it possible to select the candidate population and the possibility of offering a study suited to the risk of individuals who are not susceptible to population screening by means of FOBT.

Mechanisms of colon cancer prevention with and beyond COX-2 inhibition.

Colorectal cancer is the most common cancer in Western countries and the second leading cause of cancer-related death. Sporadic lesions represent 75-80% of all colorectal cancer, whereas 20-25% are in younger individuals or in patients with a family history of cancer, suggesting a heritable susceptibility. Persons with germline alterations in cancer-promoting genes, such as those with familial adenomatous polyposis and hereditary non-polyposis colorectal cancer, stand to benefit significantly from chemopreventive interventions, along with those who had already developed any colorectal neoplasia (either adenoma or carcinoma). Among the most promising approaches to chemoprevention is the use of non-steroidal anti-inflammatory drugs, including both selective and non-selective cyclooxigenase-2 inhibitors. Although the present article is mainly focused on these drugs and their mechanisms of action, other strategies with potential involvement in colorectal cancer chemoprevention such as peroxisome proliferator activated receptor ligands, epithelial growth factor receptor blockers, calcium, vitamin D, folate, and DNA methyltransferase inhibitors are also reviewed.

The European panel on the appropriateness of gastrointestinal endoscopy guidelines colonoscopy in an open-access endoscopy unit: a prospective study.

BACKGROUND: The demand for gastrointestinal endoscopy is increasing in most developed countries, resulting in an important rise in overall costs and waiting lists for endoscopic procedures. Therefore, adherence to appropriate indications for these procedures is essential for the rational use of finite resources in an open-access system. AIM: To assess indications and appropriateness of colonoscopy according to the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria. METHODS: From May to June 2004, all consecutive patients referred to our Unit for open-access colonoscopy were considered for inclusion in this prospective study. Appropriateness of each colonoscopy was established according to the EPAGE criteria. In order to evaluate whether appropriateness of use correlated with the diagnostic yield of colonoscopy, relevant endoscopic findings were also recorded. RESULTS: A total of 350 consecutive patients were included in the study. In 38 of them, the colonoscopy indication was not listed in the EPAGE guidelines and, consequently, they were not evaluated. In the remaining 312 patients, the indication for the procedure was considered inappropriate in 73 (23%) patients. Both referring doctor characteristics (specialty and health care setting) and patient data (age) correlated with appropriateness of endoscopy. The diagnostic yield was significantly higher for appropriate colonoscopies (42%) than in those judged inappropriate (21%) (P = 0.001). CONCLUSIONS: A noteworthy proportion of patients referred for colonoscopy to an open-access endoscopy unit are considered inappropriate because of their indication, with significant differences among specialties. These results suggest that implementation of validated guidelines for its appropriate use could improve this situation and, considering the correlation between appropriateness and diagnostic yield, even contribute to improve the prognosis of patients with colorectal diseases.

Implicación de ciclooxigenasa 2 en el cáncer: utilidad de los coxib / Implication of cyclooxygenase 2 in cancer: utility of coxibs

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Clinical usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by means of endosonography-guided fine-needle aspiration biopsy.

AIM: To establish the usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by comparing this technique with conventional cytology in aspirates obtained by endosonography-guided fine-needle aspiration. METHODS: All consecutive patients with pancreatic focal lesions undergoing endosonography-guided fine-needle aspiration were included. Samples were obtained with the concurrence of an attendant cytopathologist. Detection of codon-12 KRAS mutations was performed by the restriction fragment length polymorphism-polymerase chain reaction method. The effectiveness of conventional cytology, KRAS mutational analysis and their combination was established with respect to the definitive diagnosis. A cost-effectiveness analysis was also performed. RESULTS: Thirty-three patients had pancreatic adenocarcinoma and 24 patients had other lesions. A total of 136 samples was obtained. In patients in whom specimens were adequate (93% for cytology; 100% for mutational analysis), the specificity of both techniques was 100%, whereas the sensitivity favoured cytology (97% vs. 73%). When inadequate samples were considered as misdiagnosed, a combination of both techniques reached the highest overall accuracy (cytology, 91%; mutational analysis, 84%; combination of both, 98%). CONCLUSIONS: Cytology from aspirates obtained by endosonography-guided fine-needle aspiration is the most precise single technique for the diagnosis of pancreatic adenocarcinoma. However, when adequate specimens are not available to reach a cytological diagnosis, the addition of KRAS mutational analysis represents the best strategy.