The risk of missed gastroesophageal cancer diagnoses in users and nonusers of antisecretory medication

BACKGROUND & AIMS: Some patients with early gastroesophageal cancer may appear to "heal" because of antisecretory medication, but the risk of a missed diagnosis is unknown. The aim of the study was to estimate the incidence of gastroesophageal cancer with or without pre-endoscopic treatment with antisecretory medication. METHODS: We extracted data on use of endoscopies, gastroesophageal cancer diagnoses, death, migration, and use of antisecretory medication (H(2) blockers and proton pump inhibitors) from 5 population-based registries covering 1974-2002. We included all citizens in Funen County (population, 470,000) who between 1993 and 2002 were investigated by endoscopy for the first time. The patients were followed up until death, emigration, or the end of the study period. RESULTS: Among 27,829 patients with a first endoscopy (mean age, 56 years; 48% male, 115,804 person-years of follow-up), 461 had gastroesophageal cancer diagnosed at the first endoscopy and 52 were diagnosed during a median follow-up of 2.7 years after the first endoscopy. The incidence during follow-up was similar to the background population (standardized incidence ratio, 1.24; 95% confidence interval, 0.81-1.91), increased with age, and was higher in male patients. The incidence of gastroesophageal cancer during follow-up was 46 per 100,000 person-years in users of antisecretory medication the last 180 days before the first endoscopy compared with 44 per 100,000 person-years in nonusers (age and sex standardized difference, 4 per 100,000 person-years; 95% confidence interval, -14 to 22). CONCLUSIONS: Very few cancers are missed at endoscopy. The risk seems similar in users and nonusers of antisecretory medication before endoscopy.     

Purification, immunochemical characterization, and immunohistochemical localization of rat hepatic aryl sulfotransferase IV.

Aryl sulfotransferases catalyze the formation of sulfuric acid esters from a diverse group of endogenous and xenobiotic organic chemicals. The isoenzyme of aryl sulfotransferase in livers of male Sprague-Dawley rats that exhibits the most varied substrate specificity is aryl sulfotransferase IV. A new method for the purification to homogeneity of aryl sulfotransferase IV was developed that, when compared with previously described procedures, provided a greater than 10-fold increase in total yield of enzyme/g of tissue. Homogeneous aryl sulfotransferase IV was used to prepare polyclonal antibodies in male New Zealand White rabbits. Results of immunochemical analyses demonstrated that these antibodies reacted with only a single protein in rat hepatic 100,000 x g supernatant fractions and, further, that the immunoreactive protein had the isoelectric point and subunit molecular mass characteristic of aryl sulfotransferase IV. Immunohistochemical analyses demonstrated that aryl sulfotransferase IV is present in hepatocytes throughout the liver, although centrilobular cells contain a significantly greater (p less than 0.01) amount of aryl sulfotransferase IV than do either midzonal or periportal cells, in which similar levels of the enzyme are found.     

Randomized trial of loop ileostomy in restorative proctocolectomy.

A randomized controlled trial was performed to assess the role of loop ileostomy in totally stapled restorative proctocolectomy. Entry criteria included all patients who were not on corticosteroids in whom on-table testing revealed a watertight pouch with intact ileoanal anastomosis. Of 59 patients undergoing restorative proctocolectomy over 36 months, 45 were eligible and were randomized to loop ileostomy (n = 23) or no ileostomy (n = 22). The age and diagnosis of the groups were similar. There were no deaths; two ileoanal anastomotic leaks occurred, one in each group. Ileoanal stenosis occurred in five patients with and one without an ileostomy. The incidences of wound and pelvic sepsis, bowel obstruction and pouchitis were similar. Twelve patients (52 per cent) developed ileostomy-related complications. The median total hospital stay was 23 (range 13-75) days with ileostomy and 13 (range 7-119) days without (P < 0.001). This study indicates that there is a low risk of pelvic sepsis which is not increased by avoiding a protective ileostomy. Loop ileostomy was associated with a high incidence of complications.     

Role of ectodomain lysines in the subunits of the heteromeric P2X2/3 receptor

Lysine residues near each end of the receptor ectodomain (in rat P2X2 Lys69 and Lys308) have been implicated in ATP binding to P2X receptors. We recorded membrane currents from human embryonic kidney cells expressing P2X subunits and found that lysine-to-alanine substitutions at equivalent positions in the P2X3 receptor (Lys63 and Lys299) also prevented channel function. Heteromeric P2X2/3 receptors are formed when P2X2 and P2X3 subunits are expressed together; they can be distinguished by their relatively sustained response to alphabeta-methylene-ATP. By coexpression of wild-type P2X3 and mutated P2X2 subunit, we found that the heteromeric P2X2/3 channel functioned normally when either lysine in the P2X2 subunit was mutated to alanine (i.e., [K69A] or [K308A]) but not when both lysines were mutated to alanine (i.e., [K69A, K308A]). However, coexpression of wild-type P2X2 with a mutated P2X3 subunit ([K68A] or [K299A]) produced no functional heteromers. The rescue of the single lysine mutant P2X2 subunit by wild-type P2X3 (but not the converse) suggests that the heteromeric channel contains one P2X2 and two P2X3 subunits and that the receptor functions essentially normally as long as two subunits are not mutated. The failure to rescue function in the P2X2 subunit with both lysines mutated by wild-type P2X3 suggests that these residues from two different subunits interact in agonist binding or channel opening.     

How do you measure performance as a colonoscopist?

Aim The aim of this study was to describe an easy and reproducible method of measuring clinical performance in colonoscopy. Method Data from all endoscopy procedures performed within the main endoscopy unit at Derriford Hospital between January and December 2007 were analysed. Points were allocated for given procedures. A local health economic analysis revealed that at least 8 points (or four colonoscopies) must be performed to meet list costs. The clinical performance was described as a capability index of crude Caecal Intubation Rate (CIR) vs the mean Points Performed/Endoscopy List (points/list). Results Overall, 3884 colonoscopies were performed, with a mean crude CIR of 89.6% and 8.3 points/List. Only 7/23 endoscopists consistently met the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) standard in a cost‐effective way. An annual colonoscopy rate of ≥ 150 cases was associated with higher points per list (points/list) (P = 0.003). Endoscopists offering ≥ 15% of cases as training cases had significantly higher crude CIRs and points/list (P = 0.051; P = 0.017). Conclusions Clinical performance is a function of quality provided in a cost‐effective way. Our capability index is an effective and reproducible way of measuring clinical performance. Training was not associated with reduced volume.     

Research perspectives in the etiology of congenital anorectal malformations using data of the International Consortium on Anorectal Malformations: evidence for risk factors across different populations

Purpose

The recently established International Consortium on Anorectal Malformations aims to identify genetic and environmental risk factors in the etiology of syndromic and nonsyndromic anorectal malformations (ARM) by promoting collaboration through data sharing and combined research activities.

Methods

The consortium attempts to recruit at least 1,000 ARM cases. DNA samples are collected from case–parent triads to identify genetic factors involved in ARM. Several genetic techniques will be applied, including SNP arrays, gene and whole exome sequencing, and a genome-wide association study. Questionnaires inquiring about circumstances before and during pregnancy will be used to obtain environmental risk factor data.

Results

Currently, 701 ARM cases have been recruited throughout Europe. Clinical data are available from all cases, and DNA samples and questionnaire data mainly from the Dutch and German cases. Preliminary analyses on environmental risk factors in the Dutch and German cohort found associations between ARM and family history of ARM, fever during first trimester of pregnancy and maternal job exposure to cleaning agents and solvents.

Conclusion

First results show that both genetic and environmental factors may contribute to the multifactorial etiology of ARM. The International Consortium on Anorectal Malformations will provide possibilities to study and detect important genes and environmental risk factors for ARM, ultimately resulting in better genetic counseling, improved therapies, and primary prevention.