Identification of upper gastrointestinal malignancy in patients with uncomplicated dyspepsia referred under the two-week-wait cancer pathway: a single-centre, 10-year experience.

INTRODUCTION: In the United Kingdom, the National Institute for Health and Care Excellence 2015 guidance recommend that for suspected gastric or oesophageal cancer, general practitioners consider a non-urgent, direct-access endoscopy in patients over 55 years with only uncomplicated treatment-resistant dyspepsia. In practice, patients are referred under the urgent 2-week-wait cancer pathway. METHODS: We compared the frequency of gastric or oesophageal carcinoma in patients referred to our centre on the 2-week-wait pathway with uncomplicated dyspepsia to those who have a combination of additional alarm symptoms. The four most common indications for endoscopy referral on the 2-week-wait pathway and all combinations of those indications were examined: Dyspepsia ('ulcer-like', 'non-ulcer-like' or 'reflux-like' dyspepsia), anaemia, weight loss or dysphagia. RESULTS: Over 10 years, 9012 two-week-wait gastroscopies were performed, and a tumour was identified in 256 patients (2.84%). One thousand and three hundred six gastroscopies performed for uncomplicated dyspepsia and only 6 patients (0.46%) had a tumour. Therefore, uncomplicated dyspepsia alone had a poor positive predictive value of detecting gastric or oesophageal cancer. Our findings suggest dyspepsia had no significant cumulative effect on the number of patients with anaemia or weight loss found to have a lesion at endoscopy but indeed significantly decreased the likelihood of finding a tumour in those with dysphagia. CONCLUSION: Dyspepsia as a parameter to investigate gastric or oesophageal cancer contributes significantly to the growth in number of 2-week-wait referrals at a time when endoscopy units battle to meet demand. Our data show patients with uncomplicated dyspepsia rarely have gastric or oesophageal cancer and should not undergo endoscopies under the urgent 2-week-wait pathway.

ECOLOGICAL AND EVOLUTIONARY APPLICATIONS FOR ENVIRONMENTAL SEX REVERSAL OF FISH.

Environmental sex reversal (ESR), which results in a mismatch between genotypic and phenotypic sex, is well documented in numerous fish species and may be induced by chemical exposure. Historically, research involving piscine ESR has been carried out with a view to improving profitability in aquaculture or to elucidate the processes governing sex determination and sexual differentiation. However, recent studies in evolution and ecology suggest research on ESR now has much wider applications and ramifications. We begin with an overview of ESR in fish and a brief review of the traditional applications thereof. We then discuss ESR and its potential demographic consequences in wild populations. Theory even suggests sex-reversed fish may be purposefully released to manipulate population dynamics. We suggest new research directions that may prove fruitful in understanding how ESR at the individual level translates to population-level processes. In the latter portion of the review we focus on evolutionary applications of ESR. Sex-reversal studies from the aquaculture literature provide insight in to the evolvability of determinants of sexual phenotype. Additionally, induced sex reversal can provide information about the evolution of sex chromosomes and sex-linked traits. Recently, naturally occurring ESR has been implicated as a mechanism contributing to the evolution of sex chromosomes.

Choledocholithiasis presenting with very high transaminase level.

We present three cases of choledocholithiasis presenting with a rise in transaminase to levels normally associated with acute hepatitis (alanine aminotransferase in excess of 1000 IU/l). All three cases had repeated investigation for liver disease before identification of common bile duct stones with magnetic resonance cholangiopancreatogram, and removal at endoscopic retrograde cholangiopancreatogram. We discuss the existing literature and the potential mechanisms of hepatocyte injury in extrahepatic obstruction.

Midazolam with meperidine or fentanyl for colonoscopy: results of a randomized trial.

BACKGROUND: A combination of midazolam and opioid is usually used to achieve sedation and analgesia during colonoscopy. Two commonly used opioids are meperidine and fentanyl, but few studies have compared their efficacy. OBJECTIVE: This randomized trial aimed to compare the efficacy and recovery time of 2 sedation regimens consisting of midazolam in combination with either meperidine or fentanyl. DESIGN, SETTING, AND PATIENTS: A total of 300 consecutive, unselected adults attending outpatient colonoscopy at a District General Hospital were enrolled with informed consent and randomized to receive midazolam with meperidine or fentanyl. Data for procedure times, perceived discomfort (according to standard 100-mm visual analog scales [VAS]), and recovery time were collected. Patients and all endoscopy staff directly involved with the procedure were blinded to the regimen used. MAIN OUTCOME MEASUREMENTS: Primary: patients' experience of pain (postrecovery VAS score); secondary: recovery time. RESULTS: A total of 287 patients (150 female, mean [SD] age 54 [17] years) were studied. Recovery time (in minutes) was significantly shorter in patients receiving fentanyl (n = 138) than in those receiving meperidine (n = 149, mean +/- SE: 13.7 +/- 1.8 vs 18.7 +/- 1.7, P = .03), whereas there was no difference in the patients', endoscopists', or nurses' perception of pain during the procedure between the 2 groups. Both groups received a median dose of 3 mg of midazolam (range 2-5 mg). In patients receiving lower doses (2-2.5 and 3-3.5 mg), recovery times were significantly faster with fentanyl (P < .01 and <.05, respectively), whereas at higher doses of midazolam (> or =4 mg) there was no difference between the 2 groups. LIMITATIONS: The use of VAS scores and nurse assessment of recovery time were chosen in this study because, despite their subjectivity, these measures were felt to most closely reflect true clinical practice. CONCLUSIONS: The use of fentanyl in combination with low-dose midazolam results in significantly faster recovery from sedation compared with meperidine, without any apparent loss of analgesic effect.

Gastrointestinal evaluation of anaemic patients without evidence of iron deficiency.

BACKGROUND: Bleeding lesions are commonly identified in the gastrointestinal (GI) tract of patients with iron deficiency anaemia (IDA). Gastroenterologists, however, are frequently referred patients with anaemia without supporting evidence of iron deficiency, where the merit of GI investigation is unknown. METHODS: We conducted a retrospective, case-control study to determine the prevalence of bleeding GI lesions in 100 anaemic patients without evidence of iron deficiency [noniron deficiency anemia (NIDA) group] and 271 patients with confirmed IDA (IDA group). RESULTS: The prevalence of bleeding lesions in the upper GI tract was significantly lower in NIDA patients (8%) compared with IDA patients (22.9%) (odds ratio 0.29, 95% confidence interval 0.15-0.55, P<0.0009). The prevalence of lower GI bleeding lesions was also significantly lower in NIDA patients (6.9%) compared with IDA patients (20.2%) (odds ratio 0.26, 95% confidence interval 0.12-0.57, P<0.025). No cases of GI malignancy were identified in the NIDA group, but in the IDA group 5.5% had an upper GI cancer and 10.7% colorectal cancer (P<0.002 and P<0.0002, respectively). Subgroup analysis of patients aged more than or equal to 70 years stratified according to serum ferritin concentration (low, intermediate and high), revealed that the prevalence of bleeding lesions in both the upper (26.4% vs. 23.5% vs. 2.9%) and lower (26.8% vs. 16.7% vs. 0%) GI tract did not differ significantly between patients with a low serum ferritin and intermediate serum ferritin concentrations, but was significantly lower in the low ferritin group compared with high ferritin group (P<0.003 and P<0.0001, respectively). NIDA patients were also significantly more likely to have chronic kidney disease (33%), compared with IDA patients (12%), P<0.0001, and to subsequently undergo bone marrow sampling (P<0.02) with a potential cause for their anaemia being found. CONCLUSION: GI bleeding lesions are infrequently found in anaemic patients without evidence of iron deficiency and alternative causes should first be sought. Elderly patients, however, with an intermediate ferritin concentration (30-100 microg/l) also had a high yield of bleeding lesions and should be considered for GI evaluation.

Terminal ileal photography or biopsy to verify total colonoscopy: does the endoscope agree with the microscope?

BACKGROUND: Various modalities exist to document the extent of colonoscopy, including a terminal ileum (TI) biopsy, which is considered the criterion standard by some authorities. A TI biopsy adds to procedure costs, is potentially hazardous, and the detection of pathology in routinely acquired biopsy specimens of a macroscopically normal TI is limited. A safer, less costly alternative for documenting total colonoscopy is desirable. OBJECTIVE: To evaluate the effectiveness of TI photography as a means of documenting total colonoscopy. We also assessed the diagnostic yield of TI biopsies in patients with a macroscopically normal TI. DESIGN: Prospective, observational study. SETTING: District general hospital in the United Kingdom. PATIENTS: A total of 232 unselected patients undergoing colonoscopy, TI intubation, photography, and biopsy. MAIN OUTCOME MEASUREMENTS: Independent, experienced endoscopists were asked to state whether villi (and, therefore, TI entry) were "definitely," "probably," or "definitely not" depicted in TI photographs. This was compared with TI histology as a means of verifying total colonoscopy. The diagnostic yield of biopsy specimens from a macroscopically normal TI was determined. RESULTS: Reviewers agreed that villi were "definitely present" in 93.8%, "probably present" in 5.9%, and "definitely not" present in 0.3% of cases, with excellent interobserver agreement (kappa value = 0.778, P < .0001). TI photographs "definitely" depicting villi (93.8%) did not differ significantly from histology confirming TI mucosa (96.1%, P = .285). Microscopic evidence of pathology was only detectable in 2.3% of patients with an endoscopically normal TI. CONCLUSIONS: TI photography is an effective, safe, and cost-effective means of documenting total colonoscopy. Routine biopsy of a "normal" TI has a low diagnostic yield.

Gallstone ileus following endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy.

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (ES) is the treatment of choice for common bile duct (CBD) stones. Complication rates of 5-15%, and mortality rates of 1.0% have been reported. We report a case of gallstone ileus presenting 12 days after ERCP and ES.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

BACKGROUND AND AIMS: Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. METHODS: Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. RESULTS: Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. CONCLUSIONS: Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.